113 results on '"Harvey, H."'
Search Results
2. Selective Equatorial Sclera Crosslinking in the Orbit Using a Metal-Coated Polymer Waveguide
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Theo Seiler, Andreas C. Liapis, Moonseok Kim, Sheldon J. J. Kwok, Seok Hyun Yun, Christian Wertheimer, Reginald Birngruber, Harvey H. Lin, Irene E. Kochevar, Sarah Forward, and Theo G. Seiler
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Optical fiber ,Materials science ,Silver ,genetic structures ,Polymers ,Ultraviolet Rays ,Riboflavin ,610 Medicine & health ,02 engineering and technology ,waveguide ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Coated Materials, Biocompatible ,law ,Elastic Modulus ,medicine ,Animals ,crosslinking ,myopia ,Optical Fibers ,Leakage (electronics) ,chemistry.chemical_classification ,Photosensitizing Agents ,Polydimethylsiloxane ,Polymer ,021001 nanoscience & nanotechnology ,Cladding (fiber optics) ,Fluorescence ,eye diseases ,Sclera ,Biomechanical Phenomena ,medicine.anatomical_structure ,Cross-Linking Reagents ,chemistry ,030221 ophthalmology & optometry ,sense organs ,Collagen ,Rabbits ,Anatomy and Pathology/Oncology ,sclera ,0210 nano-technology ,Waveguide ,Orbit ,Biomedical engineering - Abstract
Purpose Photochemical crosslinking of the sclera is an emerging technique that may prevent excessive eye elongation in pathologic myopia by stiffening the scleral tissue. To overcome the challenge of uniform light delivery in an anatomically restricted space, we previously introduced the use of flexible polymer waveguides. We presently demonstrate advanced waveguides that are optimized to deliver light selectively to equatorial sclera in the intact orbit. Methods Our waveguides consist of a polydimethylsiloxane cladding and a polyurethane core, coupled to an optical fiber. A reflective silver coating deposited on the top and side surfaces of the waveguide prevents light leakage to nontarget, periorbital tissue. Postmortem rabbits were used to test the feasibility of in situ equatorial sclera crosslinking. Tensometry measurements were performed on ex vivo rabbit eyes to confirm a biomechanical stiffening effect. Results Metal-coated waveguides enabled efficient light delivery to the entire circumference of the equatorial sclera with minimal light leakage to the periorbital tissues. Blue light was delivered to the intact orbit with a coefficient of variation in intensity of 22%, resulting in a 45 ± 11% bleaching of riboflavin fluorescence. A 2-fold increase in the Young's modulus at 5% strain (increase of 92% P < 0.05, at 25 J/cm2) was achieved for ex vivo crosslinked eyes. Conclusions Flexible polymer waveguides with reflective, biocompatible surfaces are useful for sclera crosslinking to achieve targeted light delivery. We anticipate that our demonstrated procedure will be applicable to sclera crosslinking in live animal models and, potentially, humans in vivo.
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- 2019
3. Flexible Optical Waveguides for Uniform Periscleral Cross-Linking
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Seok Hyun Yun, Theo G. Seiler, Theo Seiler, Harvey H. Lin, Irene E. Kochevar, Peng Shao, Eric Beck, Moonseok Kim, and Sheldon J. J. Kwok
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0301 basic medicine ,Materials science ,genetic structures ,Swine ,Ultraviolet Rays ,myopia control ,610 Medicine & health ,STRIPS ,Elastomer ,Waveguide (optics) ,law.invention ,Cornea ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Optics ,law ,Elastic Modulus ,medicine ,Myopia ,Animals ,Fiber ,Irradiation ,Polydimethylsiloxane ,business.industry ,Stiffness ,sclera reinforcement ,eye diseases ,Sclera ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Cross-Linking Reagents ,chemistry ,Photochemotherapy ,030221 ophthalmology & optometry ,Optometry ,Anatomy and Pathology/Oncology ,Collagen ,sense organs ,medicine.symptom ,photo–cross-linking ,business ,optical waveguide - Abstract
Purpose Scleral cross-linking (SXL) with a photosensitizer and light is a potential strategy to mechanically reinforce the sclera and prevent progressive axial elongation responsible for severe myopia. Current approaches for light delivery to the sclera are cumbersome, do not provide uniform illumination, and only treat a limited area of sclera. To overcome these challenges, we developed flexible optical waveguides optimized for efficient, homogeneous light delivery. Methods Waveguides were fabricated from polydimethylsiloxane elastomer. Blue light (445 nm) is coupled into the waveguide with an input fiber. Light delivery efficiency from the waveguide to scleral tissue was measured and fit to a theoretical model. SXL was performed on fresh porcine eyes stained with 0.5% riboflavin, using irradiances of 0, 25, and 50 mW/cm2 around the entire equator of the eye. Stiffness of scleral strips was characterized with tensiometry. Results Light delivery with a waveguide of tapered thickness (1.4-0.5 mm) enhanced the uniformity of light delivery, compared to a flat waveguide, achieving a coefficient of variation of less than 10%. At 8% strain, sclera cross-linked with the waveguides at 50 mW/cm2 for 30 minutes had a Young's modulus of 10.7 ± 1.0 MPa, compared to 5.9 ± 0.5 MPa for no irradiation, with no difference in stiffness between proximally and distally treated halves. The stiffness of waveguide-irradiated samples did not differ from direct irradiation at the same irradiance. Conclusions We developed flexible waveguides for periscleral cross-linking. We demonstrated efficient and uniform stiffening of a 5-mm-wide equatorial band of scleral tissue.
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- 2017
4. Differential preventive activity of sulindac and atorvastatin in Apc
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Wen-Chi L, Chang, Christina, Jackson, Stacy, Riel, Harry S, Cooper, Karthik, Devarajan, Harvey H, Hensley, Yan, Zhou, Lisa A, Vanderveer, Minhhuyen T, Nguyen, and Margie L, Clapper
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Adenoma ,Male ,cancer prevention ,Colon ,Antineoplastic Agents ,colorectal adenomas ,digestive system diseases ,Mice ,Sulindac ,colonoscopy ,familial adenomatous polyposis ,Atorvastatin ,Animals ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Colorectal Neoplasms - Abstract
Objective The response of subjects to preventive intervention is heterogeneous. The goal of this study was to determine if the efficacy of a chemopreventive agent differs in non-tumour-bearing animals versus those with colorectal tumours. Sulindac and/or atorvastatin was administered to Apc+/Min-FCCC mice with known tumour-bearing status at treatment initiation. Design Male mice (6–8 weeks old) underwent colonoscopy and received control chow or chow with sulindac (300 ppm), atorvastatin (100 ppm) or sulindac/atorvastatin. Tissues were collected from mice treated for 14 weeks (histopathology) or 7 days (gene expression). Cell cycle analyses were performed on SW480 colon carcinoma cells treated with sulindac, atorvastatin or both. Results The multiplicity of colorectal adenomas in untreated mice bearing tumours at baseline was 3.6-fold higher than that of mice that were tumour free at baseline (P=0.002). Atorvastatin completely inhibited the formation of microadenomas in mice that were tumour free at baseline (P=0.018) and altered the expression of genes associated with stem/progenitor cells. Treatment of tumour-bearing mice with sulindac/atorvastatin led to a 43% reduction in the multiplicity of colorectal adenomas versus untreated tumour-bearing mice (P=0.049). Sulindac/atorvastatin increased the expression of Hoxb13 and Rprm significantly, suggesting the importance of cell cycle regulation in tumour inhibition. Treatment of SW480 cells with sulindac/atorvastatin led to cell cycle arrest (G0/G1). Conclusions The tumour status of animals at treatment initiation dictates response to therapeutic intervention. Atorvastatin eliminated microadenomas in tumour-free mice. The tumour inhibition observed with Sul/Atorva in tumour-bearing mice was greater than that achieved with each agent.
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- 2017
5. Detection and Response to Food versus Conspecific Tissue in the Crayfish Cambarus bartonii (Fabricius, 1798) (Decapoda, Cambaridae)
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Ciruna, K. A., Dunham, D. W., and Harvey, H. H.
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- 1995
6. Comparison of laparoscopic performance in vivo with performance measured in a laparoscopic simulator
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Harvey H. Sigman, J. Bothwell, Anna M. Derossis, and Gerald M. Fried
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medicine.medical_specialty ,business.industry ,Teaching ,education ,Internship and Residency ,Laparoscopic skill ,behavioral disciplines and activities ,Extracorporeal ,Surgery ,Occupational training ,General Surgery ,medicine ,Laparoscopic simulator ,Animals ,Humans ,Laparoscopy ,Clinical Competence ,business ,psychological phenomena and processes - Abstract
Laparoscopic skill was measured objectively through a series of seven tasks in an inanimate laparoscopic simulator. Seven analogous skills were tested in an in vivo porcine model. These skills included transferring, cutting, clipping, placement of a ligating loop, mesh placement, and suturing with an intracorporeal and extracorporeal knot. Scoring of each task rewarded precision and speed.Twelve PGY3 residents were given a baseline evaluation in the simulator and in the animal model. They were then randomized to either five practice sessions in the simulator (group A) or no practice (group B). Each group was retested in the simulator and in the animal (final test). Scores in vivo were compared by t-test for baseline versus final evaluation for each group. Linear regression analysis was used to correlate in vivo and in vitro scores for each task and for the total score (sum of all scores).Group A showed significant improvement in performance in vivo for cutting, clipping, mesh placement, and suturing with an intracorporeal and extracorporeal knot, as well as in the total score (p0.05). Group B showed significant improvement in suturing with an intracorporeal and extracorporeal knot, and in the total score. The magnitude of improvement from baseline to final evaluation was significantly greater for group A (p0.05). There was significant correlation between in vitro and in vivo total scores and the score for each task (p0.05) except for placement of the ligating loop and mesh.Performance in an in vitro laparoscopic simulator correlated significantly with performance in an in vivo animal model. Practice in the simulator resulted in improved performance in vivo.
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- 1999
7. Differential regulation of GRP78 and GLUT1 expression in 3T3-L1 adipocytes
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Susan C. Frost, Harvey H. Kitzman, Robert J. McMahon, Payal M. Fadia, and Ara M. Aslanian
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medicine.medical_specialty ,DNA, Complementary ,Glycosylation ,Monosaccharide Transport Proteins ,Clinical Biochemistry ,Mannose ,Carbohydrate metabolism ,Mice ,chemistry.chemical_compound ,Internal medicine ,Heat shock protein ,Gene expression ,Adipocytes ,medicine ,Animals ,RNA, Messenger ,Endoplasmic Reticulum Chaperone BiP ,Molecular Biology ,Heat-Shock Proteins ,Regulation of gene expression ,Glucose Transporter Type 1 ,biology ,Tunicamycin ,Glucose transporter ,3T3 Cells ,Cell Biology ,General Medicine ,Glucose ,Endocrinology ,Gene Expression Regulation ,chemistry ,biology.protein ,GLUT1 ,Carrier Proteins ,Molecular Chaperones - Abstract
We tested the hypothesis that the constitutive glucose transporter (GLUT 1) in 3T3-L 1 adipocytes belongs to the family of glucose-regulated proteins which are transcriptionally regulated by glucose deprivation. Using cDNA probes for both GRP78 (BiP) and GLUT1, we show that the level of GRP78 mRNA increased by 15-fold within 24 h of glucose deprivation with little change in GLUT1 mRNA. The elevated GRP78 mRNA in turn led to a time-dependent increase in GRP78 protein. While glucose deprivation did not alter the expression of the normal glycoform of GLUT 1, a lower molecular weight glycoform accumulated with extended deprivation. Mannose and fructose, but not galactose, prevented the induction of GRP78 and accumulation of the abnormal GLUT1. Because GRP78 acts as a chaperone in other cell systems, we also sought evidence to support this activity in 3T3-L1 adipocytes. Using the technique of co-immunoprecipitation, we demonstrate that GRP78 bound several proteins unique to the glucose-deprived state. No deprivation-specific proteins could be detected in association with GLUT 1. These data lead us to conclude that GLUTl does not display characteristics of the glucose-regulated proteins, at least in 3T3-L1 adipocytes, a widely used model for differentiation, hormone action, and nutrient control. However, the mechanisms for activating traditional members of this family appear intact.
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- 1996
8. Estrogen Receptor Immunostaining in the Preoptic Area and Medial Basal Hypothalamus of Estradiol Benzoate- and Prazosin-Treated Female Guinea-Pigs
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Joan I. Morrell, Karl F. Malik, and Harvey H. Feder
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medicine.medical_specialty ,medicine.drug_class ,Ovariectomy ,Endocrinology, Diabetes and Metabolism ,Guinea Pigs ,Hypothalamus, Middle ,Estrogen receptor ,Biology ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Endocrinology ,Internal medicine ,medicine ,Prazosin ,Animals ,Estrogen binding ,Estradiol ,Endocrine and Autonomic Systems ,Antibodies, Monoclonal ,Immunohistochemistry ,Preoptic Area ,Preoptic area ,Receptors, Estrogen ,chemistry ,Hypothalamus ,Estrogen ,Estradiol benzoate ,Ovariectomized rat ,Female ,medicine.drug - Abstract
Evidence has accumulated showing that the alpha 1-adrenergic antagonist prazosin decreases nuclear estrogen binding in the hypothalamus of the guinea-pig. In this study we asked if prazosin treatment alters estrogen receptor (ER) protein content as reflected by changes in ER-immunoreactivity. The monoclonal rat antibody H222 directed against ER was used to detect ER-immunoreactive (ER-ir) cells in eight specific preoptic and hypothalamic brain regions of ovariectomized Hartley strain guinea-pigs treated with estradiol benzoate and 1.0 mg/kg prazosin or vehicle. Immunocytochemical parameters which provided optimum conditions for detection of even modest changes in ER-immunoreactivity were first established. Then, using these optimum conditions, we compared 1) the mean number of ER-ir profiles, 2) the mean density of ER-ir staining, and 3) the distribution of ER-ir staining density readings, between conditions within each of the eight brain regions. No differences in any of these measures were found between prazosin- and vehicle-treated females. We also compared the percentage of ER-ir nuclear profiles across the eight cell groups investigated in estradiol benzoate- and vehicle-treated females. The medial preoptic area had by far the highest percentage (48%) of ER-ir profiles (P < 0.05) compared to all seven other brain regions (23% to 32% ER-ir cells). Our data, showing that ER-immunoreactivity is not reduced (6h) after prazosin treatment, suggests that mechanisms other than alterations in ER protein should be considered when interpreting the effects of prazosin on the retention of estradiol by nuclear or cytosolic extracts of hypothalamic lysates.
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- 1993
9. Neonatal prazosin exposure reduces ovarian weight and estrogen receptor binding in adult female rats
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Roslyn Holly Fitch and Harvey H. Feder
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Male ,medicine.medical_specialty ,medicine.drug_class ,Ovary ,Biology ,Rats, Sprague-Dawley ,Cytosol ,Developmental Neuroscience ,Internal medicine ,medicine ,Prazosin ,Animals ,Estrogen binding ,Estrogen receptor binding ,Body Weight ,Uterus ,Brain ,Organ Size ,Rats ,Preoptic area ,medicine.anatomical_structure ,Endocrinology ,Animals, Newborn ,Receptors, Estrogen ,Estrogen ,Hypothalamus ,Ovariectomized rat ,Female ,hormones, hormone substitutes, and hormone antagonists ,Developmental Biology ,medicine.drug - Abstract
Exposure of estrogen treated adult female guinea pigs to the alpha-1 antagonist prazosin has been shown to reduce levels of estrogen binding in the hypothalamus and preoptic area. To further investigate this interaction between the noradrenergic and neuroendocrine axes, newborn female rat pups received an s.c. implant of prazosin (0.0125 mg/day for 5 days) or placebo. In adulthood, subjects were sacrificed by perfusion with DMSO on the morning of proestrous. Tissue analysis of the medial preoptic area, corticomedial amygdala, and mediobassal hypothalamus revealed that cytosolic estrogen binding was significantly reduced in all three areas for the prazosin treated group as compared to controls. Ovarian weight was also significantly reduced in the prazosin treated group, although uterine weight was unaffected. Interestingly, prazosin treated females showed a post-pubertal increase in body weight characteristic of ovariectomized females, while controls showed no such increase. These results support the existence of a significant developmental interaction between the noradrenergic system and the neuroendocrine axis as measured by ovarian weight and estrogen binding in the brain.
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- 1992
10. Hepatic lipase promotes a loss of apolipoprotein A-I from triglyceride-enriched human high density lipoproteins during incubation in vitro
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M. A. Clay, Harvey H Newnham, and Philip J. Barter
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Adult ,Male ,medicine.medical_specialty ,Very low-density lipoprotein ,Apolipoprotein B ,Immunoblotting ,chemistry.chemical_compound ,Dogs ,Reference Values ,In vivo ,Internal medicine ,Cholesterylester transfer protein ,medicine ,Animals ,Humans ,Apolipoproteins A ,Triglycerides ,Hypertriglyceridemia ,Chromatography ,Lipoprotein lipase ,Apolipoprotein A-I ,biology ,Triglyceride ,Hydrolysis ,nutritional and metabolic diseases ,Lipase ,medicine.disease ,Endocrinology ,Liver ,Biochemistry ,chemistry ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Hepatic lipase ,Lipoproteins, HDL ,Cardiology and Cardiovascular Medicine - Abstract
Studies have been performed to investigate a possible mechanism to account for the low concentrations of apolipoproteins A-I (apo A-I) in subjects with hypertriglyceridemia. Incubation of human plasma in vitro with canine hepatic lipase resulted in the hydrolysis of approximately half the triglyceride in the high density lipoproteins (HDLs), but little change in the concentrations of other HDL constituents. However, when the plasma was supplemented with cholesteryl ester transfer protein and very low density lipoproteins to enrich the HDL with triglyceride, hepatic lipase promoted not only a significant reduction in HDL triglyceride acquired by the lipid transfer process but also an enhanced transfer of cholesteryl esters out of the particles. These changes were accompanied by a marked loss of apo A-I from HDL, which was demonstrated independently by ultracentrifugation, size-exclusion chromatography, and gradient gel-immunoblot analysis. The apo A-I lost from HDL was recovered in the "lipoprotein-free" fraction of plasma. The results of these studies indicate that primary reductions in the concentration of HDL core lipids in vitro are accompanied by a secondary loss of apo A-I from HDL. While recognizing the need for caution in any extrapolation from observations made in vitro to what may occur in vivo, these studies are nevertheless consistent with a proposition that the low concentration of apo A-I in subjects with hypertriglyceridemia is secondary to the reduced concentration of HDL core lipids in such subjects.
- Published
- 1991
11. Effects of Pirenzepine on Acute Mucosal Erosions, Gastric Acid and Mucosal Blood Flow in the Spinal Rat Stomach
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Anton Gillich, Martin Poleski, and Harvey H. Sigman
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Hemodynamics ,Gastroenterology ,Gastric Acid ,Lesion ,Stress, Physiological ,Internal medicine ,Muscarinic acetylcholine receptor ,medicine ,Animals ,Stomach Ulcer ,Spinal Cord Injuries ,Chemotherapy ,business.industry ,Stomach ,Antagonist ,Rats, Inbred Strains ,Pirenzepine ,Rats ,Surgery ,medicine.anatomical_structure ,Gastric Mucosa ,Regional Blood Flow ,Gastric acid ,Antacids ,medicine.symptom ,business ,medicine.drug - Abstract
The aim of this study was to examine the effects of varying doses of pirenzepine, a selective muscarinic subtype M1 antagonist, on the prevention of acute gastric mucosal lesions in male Sprague-Dawley rats subjected to spinal cord section at the C7 level. It was also intended to evaluate the effects of the drug on gastric acid output and gastric mucosal blood flow. Pirenzepine 1, 2.5 and 5 mg/kg every 2 h all caused a significant reduction in mean total ulcer length (p less than 0.01) compared to controls. This was associated with a significant decrease in acid output (p less than 0.05). There was no significant effect on gastric mucosa blood flow as measured by hydrogen gas clearance. These results indicate that the protective effects of pirenzepine on gastric mucosa, in the spinal rat model, are associated with the acid-inhibitory action of the drug and not on mucosal blood flow effects.
- Published
- 1991
12. GABAergic Control of Receptivity in the Female Rat
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David B. Masters, Harvey H. Feder, Ana María López-Colomé, Margaret M. McCarthy, Barry R. Komisaruk, Carlos Beyer, and Jeannie M. Fiber
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medicine.medical_specialty ,Lordosis ,Ovariectomy ,Endocrinology, Diabetes and Metabolism ,Posture ,Central nervous system ,Hypothalamus ,Receptivity ,Biology ,Sexual Behavior, Animal ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Diencephalon ,Endocrinology ,Internal medicine ,medicine ,Animals ,Neurotransmitter ,Progesterone ,gamma-Aminobutyric Acid ,Cerebral Cortex ,Estradiol ,Muscimol ,Endocrine and Autonomic Systems ,Rats, Inbred Strains ,medicine.disease ,Preoptic Area ,Rats ,medicine.anatomical_structure ,chemistry ,GABAergic ,Female - Abstract
GABAergic neurotransmission has been implicated in the control of the steroid-dependent behavior, lordosis. GABA has dual effects on lordosis: it facilitates lordosis through actions in the medial hypothalamus (mHYP) and it inhibits lordosis through actions in the preoptic area (POA). In the present study, gonadally intact and ovariectomized female rats were behaviorally tested with a sexually active male. Brains were removed from sexually receptive female either 1 or 24 h after behavioral testing. There was a significant difference in endogenous GABA concentration in HYP and POA between receptive, postreceptive and ovariectomized nonreceptive females. Specifically, GABA levels in postreceptive females were higher in the HYP (20%) and lower in the POA (21%) in comparison to receptive females (p less than 0.05). There was also a significant change in binding parameters of 3H-muscimol in the HYP and POA of receptive females as compared to 24 h postreceptive and ovariectomized rats. Attempts to modulate 3H-GABA release from hypothalamic tissue slices by estrogen or progesterone in ovariectomized rats yielded no effect on this parameter.
- Published
- 1991
13. Progestin receptors in the ventromedial nucleus of the hypothalamus and arcuate nucleus-median eminence are decreased by idazoxan
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Patricia A. Vincent and Harvey H. Feder
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medicine.medical_specialty ,Lordosis ,Guinea Pigs ,Promegestone ,Dioxanes ,Cytosol ,Idazoxan ,Arcuate nucleus ,Internal medicine ,polycyclic compounds ,medicine ,Prazosin ,Animals ,Tissue Distribution ,Receptor ,Molecular Biology ,Adrenergic alpha-Antagonists ,Chemistry ,General Neuroscience ,Osmolar Concentration ,Arcuate Nucleus of Hypothalamus ,Median Eminence ,medicine.disease ,Lordosis behavior ,Ventromedial nucleus of the hypothalamus ,Endocrinology ,Ventromedial Hypothalamic Nucleus ,Median eminence ,Female ,Neurology (clinical) ,Receptors, Progesterone ,hormones, hormone substitutes, and hormone antagonists ,Developmental Biology ,medicine.drug - Abstract
Steroid-dependent lordosis behavior in ovariectomized (OVX) guinea pigs is attenuated by alpha 1- and/or alpha 2-noradrenergic (NE) receptor antagonists. Correlated with the decrease in lordosis after alpha 1-NE receptor blockade by prazosin is a decrease in 'cytosol' progestin receptors in the ventromedial hypothalamic nucleus (VMN). We examined whether a presumed alpha 2-NE receptor blocker (idazoxan, IDA) also affects progestin receptors. A decrease in 'cytosol' progestin receptors was found after IDA treatment of OVX, estrogen-treated guinea pigs in the VMN and the arcuate nucleus-median eminence (ARC-ME). Apparently, either prazosin or IDA can inhibit lordosis behavior and decrease 'cytosol' progestin receptors in the VMN. In contrast, idazoxan but not prazosin, decrease 'cytosol' progestin receptors in the ARC-ME.
- Published
- 1990
14. Synergistic effects of lipid transfers and hepatic lipase in the formation of very small high-density lipoproteins during incubation of human plasma
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Harvey H Newnham and Philip J. Barter
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Adult ,Male ,medicine.medical_specialty ,Very low-density lipoprotein ,food.ingredient ,Sterol O-acyltransferase ,Biophysics ,Lipoproteins, VLDL ,Biochemistry ,Lecithin ,Dogs ,Endocrinology ,food ,Internal medicine ,Cholesterylester transfer protein ,Blood plasma ,medicine ,Animals ,Humans ,Particle Size ,Glycoproteins ,Lipoprotein lipase ,biology ,Chemistry ,nutritional and metabolic diseases ,Drug Synergism ,Lipase ,Cholesterol Ester Transfer Proteins ,carbohydrates (lipids) ,Liver ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Hepatic lipase ,Carrier Proteins ,Lipoprotein - Abstract
Studies have been performed to determine the involvement of very-low-density lipoproteins (VLDL), cholesteryl ester transfer protein (CETP) and hepatic lipase (HL) in the formation of very small HDL particles. Human whole plasma has been incubated for 6 h at 37° C in the absence and in the presence of various additions. There was minimal formation of very small HDL in incubations of non-supplemented plasma or in plasma supplemented with either VLDL, CETP or HL alone; nor were small HDL prominent after incubating plasma supplemented with mixtures of VLDL plus CETP, VLDL plus HL or CETP plus HL. By contrast, when plasma was supplemented with a mixture containing all three of VLDL, CETP and HL, incubation resulted in an almost total conversion of the HDL fraction into very small particles of radius 3.7 nm. The appearance of these very small HDL was independent of activity of lecithin:cholesterol acyltransferase. It was, however, dependent on both duration of incubation and on the concentrations of the added VLDL, CETP and HL. The effects of these incubations was also assessed in terms of changes to the concentration and distribution of lipid constituents across the lipoprotein spectrum. It was found that not only did lipid transfers and HL exhibit a marked synergism in promoting a reduction in HDL particle size but also that HL, although deficient in intrinsic transfer activity, enhanced the CETP-mediated transfers of cholesteryl esters from HDL to other lipoprotein fractions.
- Published
- 1990
15. Increased GABAergic transmission in medial hypothalamus facilitates lordosis but has the opposite effect in preoptic area
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Harvey H. Feder, Margaret M. McCarthy, and Karl F. Malik
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endocrine system ,medicine.medical_specialty ,Lordosis ,Posture ,Hypothalamus, Middle ,Bicuculline ,Sexual Behavior, Animal ,chemistry.chemical_compound ,Internal medicine ,medicine ,Animals ,Molecular Biology ,gamma-Aminobutyric Acid ,Muscimol ,Chemistry ,GABAA receptor ,General Neuroscience ,Rats, Inbred Strains ,medicine.disease ,Preoptic Area ,Rats ,Preoptic area ,Endocrinology ,nervous system ,Hypothalamus ,Estradiol benzoate ,GABAergic ,Female ,Neurology (clinical) ,Developmental Biology ,medicine.drug - Abstract
The role of γ-aminobutyric acid (GABA) in mediation of lordosis in the rat has been unclear. We report here that GABA plays a dual role in the mediation of lordosis and has differential effects in the medial hypothalamus (MH) and preoptic area/anterior hypothalamus continuum (POA-AH). Bilateral infusion of the GABAA antagonist bicuculline into the MH of cannulated females primed with estradiol benzoate and progesterone (EB+P) resulted in a marked and transient inhibition of ongoing lordosis. A similar pattern of inhibition was seen in females treated with EB only. In contrast, infusion of the same dose of bicuculline into the POA-AH of sexually receptive females had no effect on lordosis whereas infusion of the GABAA agonist muscimol into this site resulted in a short-term inhibition of lordosis. Furthermore, when females were treated with subthreshold doses of EB + P to induce a low level of lordosis responding, infusion of muscimol into the MH resulted in a significant enhancement of lordosis; infusion of bicuculline into the POA-AH also enhanced lordosis responding as compared to saline-infused controls. These data indicate that increased GABAergic neurotransmission in the MH facilitates lordosis whereas increased GABAergic activity in the POA-AH inhibits this behavior.
- Published
- 1990
16. Sarcoplasmic reticulum calcium overloading in junctin deficiency enhances cardiac contractility but increases ventricular automaticity
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Min Dong, Héctor H. Valdivia, Gerald W. Dorn, Hong-Sheng Wang, Evangelia G. Kranias, Wen Zhao, Larry R. Jones, Jason R. Waggoner, Guoxiang Chu, Abhinav Diwan, W. Keith Jones, Harvey H. Hahn, Donald M. Bers, Qunying Yuan, Guo-Chang Fan, Beth A. Altschafl, and Xiaoping Ren
- Subjects
Cardiac function curve ,Male ,medicine.medical_specialty ,Cardiotonic Agents ,Patch-Clamp Techniques ,Muscle Proteins ,Calsequestrin ,Ryanodine receptor 2 ,Mixed Function Oxygenases ,Contractility ,Electrocardiography ,Mice ,Physiology (medical) ,Internal medicine ,medicine ,Ventricular Dysfunction ,Myocyte ,Animals ,Homeostasis ,Myocytes, Cardiac ,Embryonic Stem Cells ,Mice, Knockout ,Ryanodine receptor ,business.industry ,Endoplasmic reticulum ,Calcium-Binding Proteins ,Isoproterenol ,Membrane Proteins ,Arrhythmias, Cardiac ,Myocardial Contraction ,Sarcoplasmic Reticulum ,Endocrinology ,Triadin ,Gene Expression Regulation ,cardiovascular system ,Calcium ,Female ,Cardiology and Cardiovascular Medicine ,business ,Signal Transduction - Abstract
Background— Abnormal sarcoplasmic reticulum calcium (Ca) cycling is increasingly recognized as an important mechanism for increased ventricular automaticity that leads to lethal ventricular arrhythmias. Previous studies have linked lethal familial arrhythmogenic disorders to mutations in the ryanodine receptor and calsequestrin genes, which interact with junctin and triadin to form a macromolecular Ca-signaling complex. The essential physiological effects of junctin and its potential regulatory roles in sarcoplasmic reticulum Ca cycling and Ca-dependent cardiac functions, such as myocyte contractility and automaticity, are unknown. Methods and Results— The junctin gene was targeted in embryonic stem cells, and a junctin-deficient mouse was generated. Ablation of junctin was associated with enhanced cardiac function in vivo, and junctin-deficient cardiomyocytes exhibited increased contractile and Ca-cycling parameters. Short-term isoproterenol stimulation elicited arrhythmias, including premature ventricular contractions, atrioventricular heart block, and ventricular tachycardia. Long-term isoproterenol infusion also induced premature ventricular contractions and atrioventricular heart block in junctin-null mice. Further examination of the electrical activity revealed a significant increase in the occurrence of delayed afterdepolarizations. Consistently, 25% of the junctin-null mice died by 3 months of age with structurally normal hearts. Conclusions— Junctin is an essential regulator of sarcoplasmic reticulum Ca release and contractility in normal hearts. Ablation of junctin is associated with aberrant Ca homeostasis, which leads to fatal arrhythmias. Thus, normal intracellular Ca cycling relies on maintenance of junctin levels and an intricate balance among the components in the sarcoplasmic reticulum quaternary Ca-signaling complex.
- Published
- 2007
17. Development of biochemical measures of age in the Alaskan red king crab Paralithodes camtschaticus (Anomura): Validation, refinement and initial assessment.
- Author
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Pinchuk, Alexei I., Harvey, H. Rodger, and Eckert, Ginny L.
- Subjects
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ALASKAN king crab , *CRAB populations , *CRAB reproduction , *MARINE habitats , *AGE , *ANIMALS - Abstract
Age determination of marine organisms is a central metric for understanding the timing and magnitude of spawning, recruitment and habitat use, juvenile duration, and population age structure. For crustaceans, however, age determination has been a challenge because they lack permanent hard structures and thus easily identified increments of chronology. For the commercially important red king crab Paralithodes camtschaticus , size and shell condition have been used in lieu of accurate age information for estimating population dynamics. Our goal for this validation study was to evaluate an alternative approach based on analysis of specific metabolic products. These “age pigments” collectively termed lipofuscins (LF) were used to assess P. camtschaticus age and provide a more robust metric of age than size measurements alone. For LF measurements, we relied on solvent extraction followed by HPLC separation and fluorometric quantification over histological microscopic analysis to allow higher throughput of samples for practical application in fisheries management where significant numbers of analyses are required. LF accumulation in crabs of known age reared in the laboratory under controlled conditions was tracked for calibration, with testing on P. camtschaticus from wild populations. Initial analysis showed that the P. camtschaticus fluorescence properties were broadly similar to other crustaceans but also had properties unique to this high latitude species. P. camtschaticus accumulated LF in a highly predictable manner during first four years of their lifespan consistent with observations of their increase in body size. The impact of temperature on LF accumulation was also examined in juvenile crabs 3–20 months after hatching and showed positive albeit highly variable results. Estimates of age of young P. camtschaticus from the wild population in Southeast Alaska based on LF content was in close agreement with estimates based on the population size structure and time of the spawning in the region, supporting the feasibility of the technique to provide valuable demographic information for future P. camtschaticus studies. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
18. Effects of alpha-2-adrenergic drugs in the medial preoptic area and medial basal hypothalamus on lordosis in the guinea pig
- Author
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Joan I. Morrell, Karl F. Malik, and Harvey H. Feder
- Subjects
Agonist ,medicine.medical_specialty ,Lordosis ,medicine.drug_class ,Guinea Pigs ,Posture ,Hypothalamus, Middle ,Stimulation ,Neurotransmission ,Synaptic Transmission ,Sexual Behavior, Animal ,Receptors, Adrenergic, alpha-2 ,Internal medicine ,Quinoxalines ,medicine ,Animals ,Molecular Biology ,Progesterone ,Estradiol ,Chemistry ,General Neuroscience ,Yohimbine ,medicine.disease ,Preoptic Area ,Preoptic area ,Endocrinology ,Hypothalamus ,Brimonidine Tartrate ,Ovariectomized rat ,Alpha-2 adrenergic receptor ,Female ,Neurology (clinical) ,Adrenergic alpha-Agonists ,Developmental Biology - Abstract
We have recently demonstrated that (1) stimulation of alpha-adrenergic neurotransmission in the medial basal hypothalamus (MBH) of ovariectomized (OVX) estradiol-17 beta-benzoate (EB) treated female guinea pigs activates lordotic responding and that (2) inhibition of alpha-adrenergic neurotransmission in the MBH inhibits lordotic responding in EB and progesterone (EB + P) treated females (Neuroendocrinology, in press). In this study, we investigated the relative influence of selective drugs altering alpha-2-adrenergic neuronal transmission within the MBH and medial preoptic area (MPOA) on lordotic responding in EB + P primed females. In EB + P primed females the selective alpha-2-adrenergic agonist UK-14,304 increased the number of seconds EB + P treated females held lordosis at test periods starting 15 min after infusion until test periods 1.5 h after infusion into the MPOA (maximum effect at test period 30 min after infusion, 265% vehicle (VEH); P0.005). UK-14,304 also facilitated lordotic responding 15-30 min and 1.5 h after infusion into the MBH of EB + P primed females (maximum effect at test period 30 min after infusion, 223% VEH; P0.025). Furthermore, infusing the selective alpha-2-adrenergic antagonist yohimbine (YOH) into the MBH of EB + P primed females inhibited lordotic responding between 1.0 and 2.0 h after treatment (maximum 1.5 h, 42% VEH; P0.05). These results demonstrate that alpha-2-adrenergic neurotransmission within the regions of the MPOA and the MBH facilitates lordotic responding in the guinea pig.
- Published
- 1993
19. Effects of clonidine and phentolamine infused into the medial preoptic area and medial basal hypothalamus of the guinea pig
- Author
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Karl F. Malik, Joan I. Morrell, and Harvey H. Feder
- Subjects
Agonist ,endocrine system ,medicine.medical_specialty ,Lordosis ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Guinea Pigs ,Hypothalamus, Middle ,Clonidine ,Guinea pig ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Endocrinology ,Phentolamine ,Internal medicine ,medicine ,Animals ,Infusions, Parenteral ,Endocrine and Autonomic Systems ,business.industry ,medicine.disease ,Preoptic Area ,chemistry ,Hypothalamus, Anterior ,Hypothalamus ,Estradiol benzoate ,Ovariectomized rat ,Female ,business ,Adrenergic alpha-Agonists ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
In ovariectomized (OVX) female guinea pigs sequential administration of estradiol and then progesterone (P) is usually necessary to induce the sexually receptive lordosis posture. Systemic administration of alpha-adrenergic agonists can induce lordosis in OVX guinea pigs primed with estradiol benzoate (EB) alone and facilitate lordosis in OVX females primed with EB and P. In this study, we examined the regional specificity of this regulation by infusing the alpha-adrenergic agonist clonidine (CLON) or the alpha-adrenergic antagonist phentolamine (PHEN) into discrete brain areas. CLON, infused in the medial basal hypothalamus (MBH) of EB-primed females, increased the percentage of females showing lordosis 15-45 min after infusion (p0.05) and also increased the number of seconds females held the lordosis posture 15 min to approximately 2.0 h after infusion (by as much as 65% at 15 min p0.001). CLON infused in the medial preoptic area (MPOA) of EB primed females had no effect on lordosis except at 4.0 h after infusion when it increased the number of seconds females held the lordosis posture (p0.05). In EB + P primed females, PHEN infused into the MBH transiently reduced the number of seconds EB + P primed females held lordosis from 30 min to approximately 2.0 h after infusion (by as much as 64% at 1.0 h; p0.01). Conversely, PHEN infused into the MPOA of EB + P primed females transiently increased the number of seconds females held lordosis from 15 min to 2.0 h after infusion (maximum difference 64%; p0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1993
20. Idazoxan decreases estrogen-induced lordosis in female but not 'hormone-independent' lordosis in male guinea pigs of an inbred strain
- Author
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Janice E. Thornton, Robert W. Goy, Patricia A. Vincent, Harvey H. Feder, Bruce S. McEwen, and Marc M. Roy
- Subjects
Male ,endocrine system ,medicine.medical_specialty ,Time Factors ,Lordosis ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Ovariectomy ,Guinea Pigs ,Imidazoline receptor ,Biology ,Injections ,Guinea pig ,Dioxanes ,chemistry.chemical_compound ,Endocrinology ,Idazoxan ,Internal medicine ,medicine ,Animals ,heterocyclic compounds ,Drug Interactions ,Biological Psychiatry ,Adrenergic alpha-Antagonists ,Progesterone ,Sex Characteristics ,Endocrine and Autonomic Systems ,Estrogens ,medicine.disease ,Lordosis behavior ,Psychiatry and Mental health ,nervous system ,chemistry ,Estrogen ,Ovariectomized rat ,Estradiol benzoate ,Female ,medicine.drug - Abstract
This experiment examined whether the imidazoline idazoxan (which binds to alpha-noradrenergic receptors and to imidazoline-preferring sites) interferes with hormone-dependent or hormone-independent lordosis responses. Ovariectomized (ovx) Strain 2 female guinea pigs which were sexually receptive after receiving estradiol benzoate (EB; 3 μg/d for 3 days) were injected with either idazoxan (10 mg/kg) or with vehicle at 24 hr after the last EB injection. Idazoxan significantly decreased EB-facilitated lordosis responses in these females. Castrated Strain 2 males, which show lordosis behavior without gonadal hormone administration, were injected with the same dosage of idazoxan (10 mg/kg) or with vehicle. Idazoxan did not inhibit lordosis behavior in these males.
- Published
- 1993
21. Differential Effects of Prostaglandins on Lordosis Behavior in Female Guinea Pigs and Rats
- Author
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Babetta L. Marrone, Jorge F. Rodriguez-Sierra, and Harvey H. Feder
- Subjects
Time Factors ,Guinea Pigs ,Posture ,Physiology ,Biology ,Sexual Behavior, Animal ,chemistry.chemical_compound ,Text mining ,Animals ,Castration ,Dose-Response Relationship, Drug ,Estradiol ,business.industry ,Prostaglandins E ,Prostaglandins F ,Cell Biology ,General Medicine ,Lordosis behavior ,Differential effects ,Rats ,Reproductive Medicine ,chemistry ,Sexual behavior ,Female ,business - Published
- 1979
22. Sex differences in nuclear androgen receptors in guinea pig brain and the effects of anα2 noradrenergic blocker on androgen receptors
- Author
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Harry B. Ahdieh and Harvey H. Feder
- Subjects
Male ,Testosterone propionate ,endocrine system ,medicine.medical_specialty ,medicine.drug_class ,Ovariectomy ,Guinea Pigs ,Biology ,Dioxins ,Dioxanes ,chemistry.chemical_compound ,Sex Factors ,Idazoxan ,Reference Values ,Internal medicine ,medicine ,Prazosin ,Animals ,Testosterone ,Estrenes ,Receptor ,Testosterone Congeners ,Molecular Biology ,Adrenergic alpha-Antagonists ,Cell Nucleus ,Metribolone ,General Neuroscience ,Brain ,Androgen ,Preoptic area ,Androgen receptor ,Kinetics ,Endocrinology ,chemistry ,Organ Specificity ,Receptors, Androgen ,Female ,Neurology (clinical) ,Orchiectomy ,Developmental Biology ,medicine.drug - Abstract
The binding of the synthetic androgen, [3H]methyltrienolone (R1881) to nuclear androgen receptors (NAR) was studied in various brain areas of gonadectomized male and female guinea pigs treated for 3 days with 2 mg testosterone propionate. The Scatchard analysis of salt-extracted NAR showed a single, high-affinity receptor with a Kd of 0.152 nM and maximum binding sites (Bmax) of 161.9 fmol/mg DNA. The concentration of NAR was highest in the hypothalamus (HYPO) and preoptic area (POA) in both males and females. Lower receptor levels were detected in the amygdala and cortex. NAR levels were significantly lower in the POA of females than in males. Systemic injection of prazosin, an alpha 1-adrenergic antagonist had no effect on NAR concentrations, but an alpha 2-antagonist, idazoxan, significantly reduced the binding of [3H]R1881 to NAR in both HYPO and POA. The reduction in binding of the ligand to receptor was not due to alterations in affinity of NAR, but rather to the decline in the number of receptors.
- Published
- 1988
23. Relation Between Individual Differences in Sexual Behavior and Plasma Testosterone Levels in the Guinea Pig
- Author
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Harvey H. Feder and Cheryl F. Harding
- Subjects
Male ,Estrous cycle ,medicine.medical_specialty ,Wire mesh ,Ejaculation ,Guinea Pigs ,Individuality ,Radioimmunoassay ,Biology ,Guinea pig ,Sexual Behavior, Animal ,Endocrinology ,Sexual behavior ,Internal medicine ,medicine ,Animals ,Female ,Testosterone ,Hormone - Abstract
After 3 tests for male sex behavior, adult male guinea pigs were classified as either low-activity (LA, no ejaculations) or high-activity (HA, ejaculation during at least 2 behavior tests). In one experiment, resting levels of peripheral plasma testosterone (T), measured by radioimmunoassay, did not differ between the groups (LA=2.22 +/- 0.17 ng/ml, HA=2.09 +/- 0.11 ng/ml, X +/- SEM). However, plasma T levels were significantly higher in HA males 2 min after a sex test (2.27 +/- 0.24 ng/ml) than in LA males (1.40 +/- 0.20 ng/ml). A second experiment confirmed these results and also demonstrated that exposure of HA or LA males to an estrous female placed on the opposite side of a wire mesh barrier similarly led to higher T levels in HA than in LA males. These results indicate that a) behavioral differences between HA and LA guinea pigs are not attributable to differences in resting T levels, b) HA and LA males perceive the sex test situation differently, leading to slight increases in T in HA males and slight decreases in T in LA males, and c) these changes in T level are not dependent on copulation but can be induced by mere exposure to the sight smell and/or sound of an estrous female.
- Published
- 1976
24. Differential fornix ablations and the circadian rhythmicity of adrenal corticosteroid secretion
- Author
-
Allan Siegel, Christine T. Fischette, Harvey H. Feder, Henry M. Edinger, and Barry R. Komisaruk
- Subjects
Male ,medicine.medical_specialty ,medicine.drug_class ,Hypothalamus ,Biology ,Hippocampal formation ,Hippocampus ,chemistry.chemical_compound ,Adrenal Cortex Hormones ,Corticosterone ,Internal medicine ,medicine ,Animals ,Circadian rhythm ,Molecular Biology ,Cerebral Cortex ,Afferent Pathways ,Suprachiasmatic nucleus ,General Neuroscience ,Fornix ,Subiculum ,Neural Inhibition ,eye diseases ,Circadian Rhythm ,Rats ,Endocrinology ,nervous system ,chemistry ,Optic Chiasm ,Corticosteroid ,sense organs ,Neurology (clinical) ,Supraoptic Nucleus ,psychological phenomena and processes ,Developmental Biology - Abstract
Suction ablations of the medial or lateral fornix were performed in order to transect selectively the medial corticohypothalamic tract (mcht) which originates in the anteroventral subiculum and travels in the lateral fornix terminating in the basal hypothalamus. The circadian rhythmicity of plasma adrenal corticosteroid levels was assessed in individual animals 1--2 weeks postoperatively. Ablation of the lateral fornix disrupted the periodicity of corticosteroid secretion which is normally synchronized with the light--dark cycle, whereas medial fornix ablation or neocortical ablation caused no such disruption. Group mean levels of plasma adrenal corticoids were higher in the lateral fornix-ablated animals than in the medial fornix-ablated, neocortically ablated, or intact control animals. These findings suggest that the anteroventral subiculum is important in the regulation of adrenal corticosteroid rhythmicity, and that it exerts an inhibitory influence upon corticosteroid release.
- Published
- 1980
25. Stimulation of [3H]leucine incorporation into protein by estradiol-17β or progesterone in brain tissues of ovariectomized guinea pigs
- Author
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George N. Wade and Harvey H. Feder
- Subjects
medicine.medical_specialty ,Diaphragm ,Guinea Pigs ,Population ,Hypothalamus ,Uterus ,Nerve Tissue Proteins ,Stimulation ,Tritium ,chemistry.chemical_compound ,Leucine ,Mesencephalon ,Internal medicine ,Blood plasma ,medicine ,Animals ,Castration ,education ,Molecular Biology ,Progesterone ,Cerebral Cortex ,education.field_of_study ,Estradiol ,business.industry ,General Neuroscience ,Brain ,Drug Synergism ,Blood Proteins ,Stimulation, Chemical ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Hormone receptor ,Ovariectomized rat ,Estradiol benzoate ,Female ,Neurology (clinical) ,business ,Developmental Biology - Abstract
Stimulation of tritiated-leucine incorporation into protein by estradiol-17beta or progesterone in brain tissues of ovariectomized guinea pigs was studied. 10-14 days postovariectomy guinea pigs were given 1.67-1 or 6.67-mcg estradiol benzoate 50-1 or 200-mcg progesterone 1.67-mcg estradiol benzoate plus 200-mcg progesterone or .1-ml oil vehicle subcutaneously (sc). 4 or 24 hours later females received sc 8-mcCi tritiated-leucine/100gm body weight (specific activity 42 Ci/mmole). 90 minutes later the animals were etherized and the hypothalamus mesencephalon cerebral cortex uterus diaphragm and blood plasma were analyzed for leucine incorportion into protein. 24-hour exposure to both dosages of estradiol benzoate significantly (p greater than .05) stimulated incorporation of tritiated-leucine into protein in all brain tissues and in the uterus but not in the kiaphragm or plasma. 4-hour exposure to 200-mcg progesterone significantly (p greater than .05) increased tritiated incorporation into protein of brain tissue only. Combined treatment resulted in a synergistic effect on leucine incorporation in the uterus but not in any of the brain tissues.
- Published
- 1974
26. Role of monoamines in sexual behavior of the female guinea pig
- Author
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Lawrence P. Morin, William R. Crowley, and Harvey H. Feder
- Subjects
Biogenic Amines ,Serotonin ,medicine.medical_specialty ,Dopamine ,Receptors, Drug ,Guinea Pigs ,Clinical Biochemistry ,Methysergide ,Pharmacology ,Toxicology ,Serotonergic ,Biochemistry ,Norepinephrine ,Sexual Behavior, Animal ,Behavioral Neuroscience ,Internal medicine ,medicine ,Animals ,Progesterone ,Biological Psychiatry ,Estradiol ,business.industry ,Ovary ,Dopaminergic ,Lordosis behavior ,Apomorphine ,Monoamine neurotransmitter ,Endocrinology ,Dopamine receptor ,Depression, Chemical ,Female ,business ,medicine.drug - Abstract
Ovariectomized guinea pigs, rendered sexually receptive by injections of estradiol benzoate and progesterone, were treated with drugs that are known to affect monoamine receptor activity. Treatment with the dopamine receptor stimulant apomorphine or the serotonin agonist LSD resulted in a suppression of lordosis behavior that lasted for several hours. The noradrenergic receptor stimulant chlonidine potentiated the performance of lordosis (i.e., increased the duration of individual lordosis responses), while the noradrenergic receptor blocker phenoxybenzamine abolished sexual receptivity. Administration of dopaminergic or serotonergic receptor blockers (pimozide and methysergide, respectively) did not facilitate lordosis. In fact, methysergide produced a brief inhibition of sexual behavior. The results indicate that noradrenergic neurons may be involved in the induction of female sexual behavior in the guinea pig. Dopamine, and possibly serotonin, may serve as transmitters that inhibit lordosis in this species.
- Published
- 1976
27. Prolactin-steroid influences on the thermal basis for mother–young contact in Norway rats
- Author
-
Barbara Woodside, Harvey H. Feder, Attard M, Michael Leon, Christine T. Fischette, and Siegel Hi
- Subjects
medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Rats, Inbred Strains ,General Medicine ,Core temperature ,Prolactin ,Set point ,Rats ,Steroid ,Endocrinology ,Pregnancy ,Internal medicine ,Adrenal Glands ,medicine ,Animals ,Lactation ,Female ,Castration ,Ergonovine ,Maternal Behavior ,business ,Body Temperature Regulation - Abstract
Norway rat dams have a chronic elevation in core temperature throughout the first 2 wk postpartum, a situation that makes them vulnerable to a further, acute rise in body temperature during contact with their young. Prolactin appears to contribute to the chronic elevation of maternal temperature, probably by stimulating the secretion of progesterone, which then elevates the maternal thermal set point.
- Published
- 1981
28. α1- and α2-noradrenergic receptor binding in guinea pig brain: sex differences and effects of ovarian steroids
- Author
-
Harvey H. Feder, Bruce Nock, Allan E. Johnson, and Bruce S. McEwen
- Subjects
Male ,medicine.medical_specialty ,medicine.medical_treatment ,Guinea Pigs ,Alpha (ethology) ,Biology ,Clonidine ,Steroid ,Guinea pig ,Norepinephrine ,Sex Factors ,Reference Values ,Internal medicine ,medicine ,Prazosin ,Animals ,Receptor ,Molecular Biology ,Estradiol ,General Neuroscience ,Brain ,Receptors, Adrenergic, alpha ,Preoptic area ,Kinetics ,Endocrinology ,Organ Specificity ,Female ,Neurology (clinical) ,Developmental Biology ,Hormone ,medicine.drug - Abstract
Noradrenergic transmission mediated by alpha 1-receptors is involved in the regulation of ovarian steroid-dependent reproductive processes in female guinea pigs. In addition, estradiol treatment is known to affect alpha 2-receptor binding in some steroid-sensitive regions of guinea pig brain. In these experiments, we further assessed the effects of ovarian hormones on alpha-noradrenergic receptors with quantitative autoradiographic methods. Binding of alpha 1- and alpha 2-noradrenergic receptors was measured in male and female guinea pigs treated with either estradiol or oil to determine if sex differences in steroid sensitivity might be related to differences in the distribution or modulation of alpha-receptors. In a second experiment, the possibility was tested that progesterone might alter the sensitivity to norepinephrine by modulating alpha 1- or alpha 2-receptor binding in estradiol-primed female guinea pigs. Results of these studies showed that estradiol treatment reduced alpha 1- and alpha 2-receptor binding of the ventromedial hypothalamic nucleus only in females and increased alpha 2-receptor binding in several preoptic nuclei of both sexes. Progesterone administration, however, had no effect on either alpha-receptor subtype. These studies indicate that estradiol-induced changes in alpha-receptor binding might be involved in steroid-dependent reproductive processes and in the differential responsiveness of males and females to ovarian hormones. Changes in these receptors do not appear to be involved in the stimulatory effects of progesterone on neuroendocrine processes.
- Published
- 1988
29. Inhibition of guinea pig lordosis behavior by the phenylethanolamine N-methyltransferase (PNMT) inhibitor SKF-64139: Mediation by α noradrenergic receptors
- Author
-
William R. Crowley, Bruce Nock, and Harvey H. Feder
- Subjects
medicine.medical_specialty ,Monoamine Oxidase Inhibitors ,Adrenergic receptor ,Ovariectomy ,Clonidine ,Guinea pig ,Sexual Behavior, Animal ,Behavioral Neuroscience ,Norepinephrine ,Endocrinology ,Cricetinae ,Tetrahydroisoquinolines ,Internal medicine ,medicine ,Animals ,Receptor ,Progesterone ,Dose-Response Relationship, Drug ,Estradiol ,Endocrine and Autonomic Systems ,Chemistry ,Phenylethanolamine N-Methyltransferase ,Brain ,Isoquinolines ,Lordosis behavior ,Phenylethanolamine N-methyltransferase ,Receptors, Adrenergic ,Epinephrine ,Spinal Cord ,Female ,Alpha-2 adrenergic receptor ,medicine.drug - Abstract
Experiments were undertaken to determine whether the steroid-dependent lordosis response of female guinea pigs is under adrenergic control. In initial experiments, treatment with the centrally active phenylethanolomine N-methyltransferase (PNMT; the enzyme catalyzing methylation of norepinephrine to epinephrine) inhibitor SKF-64139 inhibited lordosis behavior induced by estradiol-17 beta benzoate plus progesterone. SKF-29661, a PNMT inhibitor that does not cross the blood-brain barrier, did not affect lordosis. However, no detectable epinephrine was found in brain or spinal cord of drug- or vehicle-treated guinea pigs. This suggests that epinephrine neuronal systems do not exist in the guinea pig CNS. In agreement with this idea, the inhibitory effects of SKF-64139 on lordosis were found to be primarily attributable to the blockade of alpha noradrenergic receptors rather than to PNMT inhibition. Two lines of evidence support this conclusion. First, using in vitro receptor binding techniques, SKF-64139 was found to have a relatively high affinity for alpha 1 and particularly alpha 2 receptors in guinea pig forebrain. Second, presumably through competitive inhibition of SKF-64139 binding to alpha receptors, treatment with clonidine (an alpha receptor agonist) overrode the inhibitory effects of SKF-64139 on lordosis. Taken together, these findings indicate the possible absence of epinephrine neuronal systems in guinea pig brain and reemphasize the importance of alpha receptors in regulating steroid-dependent lordosis behavior in this species.
- Published
- 1989
30. Effects of serotonin agonists on lordosis, myoclonus, and cytoplasmic progestin receptors in guinea pigs
- Author
-
Harvey H. Feder and Lynn H. O'Connor
- Subjects
Cytoplasm ,Serotonin ,medicine.medical_specialty ,Lordosis ,medicine.drug_class ,Fenfluramine ,medicine.medical_treatment ,Guinea Pigs ,Hypothalamus ,Norepinephrine ,Sexual Behavior, Animal ,Behavioral Neuroscience ,Endocrinology ,Internal medicine ,medicine ,Animals ,Progesterone ,Injections, Intraventricular ,Dose-Response Relationship, Drug ,Estradiol ,Endocrine and Autonomic Systems ,business.industry ,Quipazine ,Lordosis behavior ,medicine.disease ,Steroid hormone ,Estrogen ,Quinolines ,Female ,Receptors, Progesterone ,business ,Muscle Contraction ,Serotonin Agonist ,medicine.drug - Abstract
Peripheral treatment with the serotonin releaser fenfluramine or the serotonin agonist quipazine abolished lordosis behavior in ovariectomized estradiol and progesterone-primed female guinea pigs. Quipazine was also effective when administered into a lateral cerebroventricle. The lowest dose of fenfluramine that induced myoclonus (10 mg/kg) was higher than the dose needed to inhibit lordosis (5 mg/kg). Therefore, it appears that myoclonus and lordosis are differentially sensitive to serotonin agonists. The effects of quipazine on lordosis were time dependent. Quipazine had no effect on lordosis when given prior to the onset of sexual receptivity. These data suggest that serotonin agonists might be effective only when progesterone has had sufficient time to induce sexual receptivity. Quipazine did not affect cytoplasmic progestin receptors in brain areas involved in steroid hormone effects on lordosis. This finding, and the finding that quipazine had no effect on lordosis when given prior to the onset of sexual receptivity, suggest increased serotonin transmission does not interfere with estrogen priming or sensitivity of hypothalamic cells to progesterone.
- Published
- 1983
31. Effects of neonatal estrogen treatment of female guinea pigs on mounting behavior in adulthood
- Author
-
R.W. Goy and Harvey H. Feder
- Subjects
Testosterone propionate ,medicine.medical_specialty ,medicine.drug_class ,Guinea Pigs ,Posture ,Biology ,Sexual Behavior, Animal ,Behavioral Neuroscience ,chemistry.chemical_compound ,Endocrinology ,Internal medicine ,medicine ,Animals ,Drug Interactions ,Testosterone ,Progesterone ,Sex Characteristics ,Sexual differentiation ,Estradiol ,Endocrine and Autonomic Systems ,Age Factors ,Lordosis behavior ,Animals, Newborn ,chemistry ,Sexual behavior ,Estrogen ,Female ,Maximum duration ,Estradiol dipropionate - Abstract
Female guinea pigs were treated with 200 μg estradiol dipropionate (ED) daily from Days 1 to 15 of life. As adults they all ovulated. After gonadectomy and estrogen-progesterone treatment in adulthood, lordosis behavior was evident and showed no decrements (compared with neonatally oil-treated controls) except for a marginal decrease in maximum duration scores. However, testosterone propionate treatment in adulthood significantly increased mounting behavior in neonatally ED-treated females compared to the controls. On the other hand, estrogen-progesterone treatment in adulthood stimulated mounting in the neonatally oil-treated group, but not in the neonatally estrogenized group. The results suggest that at least some aspects of steroid-dependent behaviors can be permanently influenced by estrogen treatment after the presumed prenatal critical period for sexual differentiation has been completed in guinea pigs.
- Published
- 1983
32. Tritium-sensitive film autoradiography of guinea pig brain α2-noradrenergic receptors
- Author
-
Harvey H. Feder, Bruce Nock, Bruce S. McEwen, and Allan E. Johnson
- Subjects
medicine.medical_specialty ,Guinea Pigs ,Hippocampus ,Biology ,Clonidine ,Guinea pig ,White matter ,Limbic system ,Species Specificity ,Internal medicine ,medicine ,Animals ,Receptor ,Molecular Biology ,General Neuroscience ,Brain ,Receptors, Adrenergic, alpha ,Rats ,Stria terminalis ,Endocrinology ,medicine.anatomical_structure ,nervous system ,Forebrain ,Biophysics ,Autoradiography ,Neurology (clinical) ,Nucleus ,Developmental Biology - Abstract
Tritium-sensitive film autoradiography was used to determine the distribution of α-noradrenergic receptors (i.e. [3H] p-aminoclonidine binding sites) in guinea pig forebrain. α2-Receptors are heterogeneously distributed throughout the forebrain. Many limbic system structures, such as bed nucleus of stria terminalis, medial preoptic area, medial amygdaloid nucleus and lacunosum molecular layer in hippocampus were heavily labeled. We did not quantify receptor density in areas containing principally white matter but the optical density in those areas was similar to film background suggesting a very low receptor density. Low receptor concentrations were also found in areas that do not contain a high percentage of white matter, such as lateral septum and ventromedial hypothalamic nucleus.
- Published
- 1985
33. A Sex Difference in the Progestin Receptor System of Guinea Pig Brain
- Author
-
Helena I. Ryer, Jeffrey D. Blaustein, and Harvey H. Feder
- Subjects
Male ,Receptors, Steroid ,medicine.medical_specialty ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Guinea Pigs ,Posture ,Hypothalamus ,Biology ,Promegestone ,Guinea pig ,Sexual Behavior, Animal ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Cytosol ,Endocrinology ,Internal medicine ,medicine ,Animals ,Castration ,Receptor ,Progesterone ,Cerebral Cortex ,Sex Characteristics ,Estradiol ,Endocrine and Autonomic Systems ,medicine.anatomical_structure ,chemistry ,Cerebral cortex ,Female ,Progestins ,Receptors, Progesterone ,Progestin ,Sex characteristics - Abstract
Female guinea pigs are more sensitive than males to the lordosis-promoting effects of sequential estradiol-progesterone treatment. This study explored a possible cellular basis for this reduced sensitivity. Cytoplasmic progestin receptor concentrations were determined using a [3H]R5020 binding assay for a dissection of brain tissue which included the hypothalamus, preoptic area and septum (HPS) from male and female guinea pigs 40 h after administration of estradiol benzoate (EB). Male guinea pigs injected with 10 micrograms EB have a progestin binder in cytosol from HPS and cerebral cortex that is similar to that in females on the basis of apparent dissociation constant and steroid specificity. Injection of either 1.6 or 10 micrograms EB caused a larger increase in the concentration of cytoplasmic progestin binding in female HPS compared to the same dose in males. A 10 microgram EB injection induced a concentration of progestin binding in male hypothalamus not significantly different from that induced in female hypothalamus by a 1.6 microgram EB injection (a dose that consistently facilitates sexual recepivity in females when followed 40 h later by 0.5 mg progesterone). Despite the induction by EB of a behaviorally-sufficient concentration of cytoplasmic progestin receptors, fewer males (3/10) than females (8/10) responded to EB (10 micrograms)-progesterone treatment with the expression of lordosis. Finally, using a nuclear progestin receptor [3H]R5020 exchange assay, we found that male guinea pigs injected with 10 micrograms EB accumulated a slightly lower concentration of progestin receptors in HPS cell nuclei 4 h after a 0.5 mg progesterone injection than similarly-treated females. Therefore, male guinea pigs show decreased induction of cytoplasmic progestin receptors in HPS after estradiol injection, and a decreased cell nuclear accumulation of these receptors after progesterone injection compared to females. We conclude that this sex difference in the progestin receptor system is insufficient to account, in itself, for the sex difference in behavioral sensitivity to estradiol and progesterone.
- Published
- 1980
34. Sex differences in cytosolic progestin receptors in microdissected regions of the hypothalamus/preoptic area of guinea pigs
- Author
-
Harvey H. Feder, Janice E. Thornton, Bruce Nock, and Bruce S. McEwen
- Subjects
Male ,endocrine system ,medicine.medical_specialty ,Guinea Pigs ,Central nervous system ,Hypothalamus ,Biology ,Promegestone ,Guinea pig ,chemistry.chemical_compound ,Cytosol ,Internal medicine ,medicine ,Animals ,Castration ,Receptor ,Molecular Biology ,reproductive and urinary physiology ,Sex Characteristics ,Estradiol ,General Neuroscience ,Preoptic area ,Endocrinology ,Ventromedial nucleus of the hypothalamus ,medicine.anatomical_structure ,nervous system ,chemistry ,Estradiol benzoate ,Female ,Neurology (clinical) ,Receptors, Progesterone ,hormones, hormone substitutes, and hormone antagonists ,Developmental Biology - Abstract
Cytosolic progestin receptors (CPRs) were measured in microdissected nuclei of the hypothalamus and preoptic area of male and female guinea pigs. Adult gonadectomized animals were given 3 daily injections of 20 micrograms/day estradiol benzoate (EB) or oil vehicle. 24 h later, animals were sacrificed and cytosolic progestin receptors were measured using the synthetic progestin 3H-R5020. CPR levels did not differ significantly between oil treated males and oil treated females in any brain areas examined. With EB treatment, males showed significant increases in CPRs in most of the brain areas in which females showed increases, i.e. in the medial preoptic area, the periventricular part of the preoptic area, the periventricular part of the anterior hypothalamus, the ventromedial nucleus of the hypothalamus, the periventricular part of the medial hypothalamus and the arcuate-median eminence. However, EB treated males showed significantly lower CPR levels than EB treated females in both the periventricular part of the preoptic area and the periventricular part of the medial hypothalamus.
- Published
- 1989
35. Lack of an effect of estrogen on endogenous RNA polymerase II in guinea pig brain
- Author
-
Josiah N. Wilcox, Harvey H. Feder, and Thomas C. Spelsberg
- Subjects
medicine.medical_specialty ,Time Factors ,medicine.drug_class ,Guinea Pigs ,RNA polymerase II ,Biochemistry ,Endocrinology ,Transcription (biology) ,Internal medicine ,medicine ,Animals ,Castration ,Receptor ,Polymerase ,Estrogen receptor beta ,Estradiol ,biology ,Brain ,Estrogens ,Biological activity ,Estrogen ,biology.protein ,Female ,RNA Polymerase II ,Estrogen receptor alpha - Abstract
An early action of estrogen in peripheral target tissues is to increase endogenous RNA polymerase II activity which precedes changes in protein synthesis. Previous reports have indicated that estrogen causes a similar increase in polymerase activity in rat brain regions containing high affinity receptors for this hormone. The present series of experiments was designed to test whether a similar action of estrogen on polymerase activity occurs in guinea pig brain, with the expectation being that this enzyme might prove to be a useful marker for the early actions of estrogen. Injections of 25 or 100 micrograms estradiol-17 beta in an ethanol-saline vehicle failed to induce significant changes in polymerase II activity in the basal hypothalamus, preoptic area-septum or cortex 1, 2, 6, 13 or 24 h after hormone administration. It is concluded that the modification of RNA polymerase II activity by estrogen is not a good marker for estrogen action in the brain. This may be due to the intrinsic heterogeneity of the tissue resulting possibly in (1) increased activity in some cells and decreased activity in other cells with no net change in overall polymerase activity after estrogen treatment (2) only a small percentage of the cells responding to the steroid with altered polymerase activity with this change not detectable when whole tissue is measured or (3) only a few genes within the cells being altered in transcription by the steroid.
- Published
- 1984
36. Multiple progesterone injections and the duration of estrus in ovariectomized guinea pigs
- Author
-
L.P. Morin and Harvey H. Feder
- Subjects
medicine.medical_specialty ,Time Factors ,Injections, Subcutaneous ,Guinea Pigs ,Radioimmunoassay ,Experimental and Cognitive Psychology ,Sexual Behavior, Animal ,Behavioral Neuroscience ,chemistry.chemical_compound ,Estrus ,Pregnancy ,Internal medicine ,medicine ,Animals ,Castration ,Progesterone ,Estrous cycle ,Estradiol ,Endocrinology ,chemistry ,Sexual behavior ,Propylene Glycols ,Sexual receptivity ,High plasma ,Estradiol benzoate ,Ovariectomized rat ,Female ,Plasma progesterone ,Pharmaceutical Vehicles ,Oils - Abstract
The duration of sexual receptivity in guinea pigs primed with 3.3 ug estradiol benzoate and given 0.1 mg progesterone 36 hr later in oil or propylene glycol vehicle was about 6–7 hr. Maintenance of elevated plasma progesterone levels (as measured by radioimmunoassay)throughout the period of heat by multiple 0.1 mg progesterone injections significantly prolonged (by about 2.7 hr) heat duration, but heat terminated despite the presence of high plasma progesterone levels. The experiment suggests that a decline in plasma progesterone concentration is not necessary for the termination of heat. Methods by which termination of heat could occur are discussed.
- Published
- 1973
37. Neurotransmitter modulation of steroid action in target cells that mediate reproduction and reproductive behavior
- Author
-
Bruce Nock and Harvey H. Feder
- Subjects
Receptors, Steroid ,medicine.medical_specialty ,Sexual Behavior ,Cognitive Neuroscience ,medicine.medical_treatment ,Population ,Hypothalamus ,Biology ,Neurotransmission ,Pineal Gland ,Synaptic Transmission ,Steroid ,Sexual Behavior, Animal ,Behavioral Neuroscience ,chemistry.chemical_compound ,Postsynaptic potential ,Internal medicine ,medicine ,Animals ,Humans ,education ,Neurotransmitter ,Neurotransmitter Agents ,education.field_of_study ,Reproduction ,Uterus ,Estrogens ,Hormones ,Neuropsychology and Physiological Psychology ,Endocrinology ,chemistry ,Hormone receptor ,Female ,Steroids ,Neuroscience ,Hormone - Abstract
Two major functional interactions between steroid hormones and neurotransmitters are generally recognized. First, steroids affect neurotransmission, and second, through effects on hypothalamic peptides that regulate anterior pituitary function neurotransmitters affect steroid secretion. In recent years, evidence has accumulated which indicates that neurotransmitters can also affect steroid action within postsynaptic steroid target cells. We review evidence for this relationship in pineal, uterus and hypothalamus and propose that the modulation of target cell responsiveness to steroids is an important mechanism by which neurotransmitters affect steroid-dependent processes. The operation of such a mechanism provides a means for environmental, behavioral and emotional events to rapidly and selectively alter steroid effects on behavior and physiology.
- Published
- 1981
38. Long Term Effects of Estrogen Action Are Crucial for the Display of Lordosis in Female Guinea Pigs: Antagonism by Antiestrogens and Correlations with inVitroCytoplasmic Binding Activity*
- Author
-
W. A. Walker and Harvey H. Feder
- Subjects
endocrine system ,medicine.medical_specialty ,Lordosis ,medicine.drug_class ,Guinea Pigs ,Posture ,Hypothalamus ,Estrogen receptor ,Caviidae ,Sexual Behavior, Animal ,Cytosol ,Endocrinology ,Internal medicine ,medicine ,Animals ,Castration ,Progesterone ,Estradiol ,biology ,Zuclomiphene ,Estrogen Antagonists ,biology.organism_classification ,medicine.disease ,Preoptic Area ,In vitro ,Kinetics ,Receptors, Estrogen ,Estrogen ,Ovariectomized rat ,Female ,hormones, hormone substitutes, and hormone antagonists - Abstract
The administration of 1.6 μg 17β-estradiol benzoate (EB) 60 h before an injection of 0.5 mg progesterone induced optimal lordosis responses in ovariectomized guinea pigs. To determine whether the presence of estrogen in neural tissue throughout the 60-h period was necessary for the display of lordosis, various antiestrogens (i.e. MER-25, CI-628, enclomiphene, or zuclomiphene) were administered during the late portion of the 60-h period. Dose-dependent inhibition of lordosis resulted when these antiestrogens were injected at 40 and 47 h after EB injection. On the other hand, injection of supplemental EB late in the priming period enhanced the display of lordosis. A correlation between behavioral antiestrogenicity and in vitro competition for cytoplasmic hypothalamic-preoptic area (H-POA) estrogen receptors was observed for all of the antiestrogens tested except MER-25. The rank order of behavioral antiestrogenic activity was: CI-628 > MER-25 = enclomiphene > zuclomiphene. The relative binding affinities of...
- Published
- 1979
39. Uptake of [6,7-3H]Estradiol-17β in ovariectomized rats, guinea pigs, and hamsters: Correlation with species differences in behavioral responsiveness to estradiol
- Author
-
George N. Wade, Harold I. Siegel, and Harvey H. Feder
- Subjects
medicine.medical_specialty ,Guinea Pigs ,Population ,Hypothalamus ,Estrone ,Tritium ,Sexual Behavior, Animal ,chemistry.chemical_compound ,Estrus ,Species Specificity ,Anterior pituitary ,Mesencephalon ,Pregnancy ,Cricetinae ,Internal medicine ,medicine ,Animals ,education ,Molecular Biology ,Cerebral Cortex ,education.field_of_study ,Dose-Response Relationship, Drug ,Estradiol ,business.industry ,General Neuroscience ,Ovary ,Uterus ,Brain ,Rats ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Hormone receptor ,Pituitary Gland ,Lordosis ,Estradiol benzoate ,Ovariectomized rat ,Female ,Neurology (clinical) ,business ,Developmental Biology ,Hormone - Abstract
The amount of estradiol benzoate with progesterone required to induce lordosis in ovariectomized hamsters was determined to compare the responsiveness of hamsters to estradiol benzoate with that of rats and guinea pigs. In addition, the uptake and metabolism of tritiated estradiol in ovariectomized rats, guinea pigs, and hamsters was examined in an attempt to correlate species differences in behavioral sensitivity to estradiol with possible differences in neural affinity for the steroid. A dose of nearly 90 mg/kg was required to induce lordosis in 100% of the hamsters compared with the 2-5 mcg/kg which is effective in rats and guinea pigs. In all 3 species, highest uptake of estradiol was in the uterus and anterior pituitary gland. In the rat and guinea pig brains, the hypothalamus took up more estradiol than either the cortex or midbrain. In the hamster, there were no consistent differences in brain uptake. The affinity of the uterus, anterior pituitary, and hypothalamus of rats and guinea pigs for estradiol was greater than that of hamsters. In all 3 species, estrone was the principal metabolite of estradiol found in the tissues. The authors suggest that the higher the endogenous levels of a steroid, the less sensitive the animal is to that steroid.
- Published
- 1974
40. Development of steroid-receptor systems in guinea pig brain. I. Cytoplasmic estrogen receptors
- Author
-
Harvey H. Feder and Helena I. Ryer
- Subjects
Male ,Cytoplasm ,Receptors, Steroid ,endocrine system ,medicine.medical_specialty ,medicine.drug_class ,Guinea Pigs ,Estrogen receptor ,Biology ,Guinea pig ,Plasma ,Sexual Behavior, Animal ,chemistry.chemical_compound ,Developmental Neuroscience ,Internal medicine ,medicine ,Animals ,Brain ,Estrogens ,Lordosis behavior ,Preoptic area ,Endocrinology ,Animals, Newborn ,Receptors, Estrogen ,chemistry ,Hypothalamus ,Estrogen ,Estradiol benzoate ,Ovariectomized rat ,Female ,hormones, hormone substitutes, and hormone antagonists ,Developmental Biology - Abstract
The development of the cytoplasmic estrogen receptor (CER) system in male and female guinea pigs was examined to determine whether attainment of sensitivity to estrogen action related to lordosis behavior is correlated with increases in brain CER concentrations. Ovariectomized neonatal (7 days old) guinea pigs failed to display lordosis after priming with 10 micrograms estradiol benzoate (EB) and 0.5 mg progesterone (P). The percentage of ovariectomized steroid-treated females displaying lordosis increased at 29-33 days of age. At 50-65 days of age this percentage increased even further. Plasma levels of estrogen in 4-6 day old animals at 4, 8 and 12 h after 10 micrograms EB were at least equal to those seen in 50-65 day old animals. Neither the concentration nor the affinity of CER in hypothalamus (HYPO), preoptic area (POA), amygdala (AMYG) and cortex ( CORT ) were different in 4-6 day olds vs 50-65 day olds. The rank order for concentrations of CER in brain regions was: POA greater than HYPO greater than AMYG greater than CORT . A sex difference in CER was found in HYPO (females greater than males), but not POA, AMYG or CORT of 4-6 day olds.
- Published
- 1984
41. Whole cell and nuclear uptake of [3H]estriol in neural and peripheral tissues of the ovariectomized guinea pig
- Author
-
Harvey H. Feder and I. Theodore Landau
- Subjects
Cell Nucleus ,medicine.medical_specialty ,Estriol ,Chemistry ,General Neuroscience ,Guinea Pigs ,Uterus ,Brain ,Tritium ,Peripheral ,Guinea pig ,Endocrinology ,Internal medicine ,medicine ,Ovariectomized rat ,Animals ,Female ,Castration ,Neurology (clinical) ,Whole cell ,Molecular Biology ,Developmental Biology - Published
- 1977
42. Estrogen Induction of Progestin Receptors in Microdissected Hypothalamic and Limbic Nuclei of Female Guinea Pigs
- Author
-
Bruce Nock, Bruce S. McEwen, Janice E. Thornton, and Harvey H. Feder
- Subjects
endocrine system ,medicine.medical_specialty ,medicine.drug_class ,Ovariectomy ,Endocrinology, Diabetes and Metabolism ,Guinea Pigs ,Hypothalamus ,Stimulation ,Biology ,Guinea pig ,Cellular and Molecular Neuroscience ,Cytosol ,Endocrinology ,Limbic system ,Internal medicine ,Limbic System ,medicine ,Animals ,Tissue Distribution ,Receptor ,reproductive and urinary physiology ,Estradiol ,Endocrine and Autonomic Systems ,Estrogens ,Kinetics ,medicine.anatomical_structure ,nervous system ,Estrogen ,Female ,Gonadotropin ,Receptors, Progesterone ,Progestin ,hormones, hormone substitutes, and hormone antagonists - Abstract
Estrogen induction of cytosolic progestin receptors (CPRs) in the hypothalamus-preoptic area of the female guinea pig is correlated with facilitation of female sexual behavior and gonadotropin secretion by progesterone. The present study validated a CPR microassay and determined where, within microdissected areas of the hypothalamus-preoptic area of the female guinea pig, induction of CPRs by estradiol occurs. Ovariectomized adult guinea pigs were given 20 micrograms estradiol benzoate (EB) or oil vehicle for 3 successive days. CPRs were measured using the synthetic progestin [3H]-R5020. The highest basal (no estrogen treatment) level of CPRs was seen in the arcuate-median eminence (34.1 +/- 3.7 fmol/mg). With EB treatment, the highest level of CPRs was again in the arcuate-median eminence (178.0 +/- 12.0 fmol/mg). EB-treated females also had high CPR levels in the periventricular area (88.5 +/- 10.8 fmol/mg) and the medial preoptic area (86.3 +/- 9.3 fmol/mg). Moderate levels were seen in the ventromedial nucleus of the hypothalamus (32.7 +/- 3.0 fmol/mg) and in the anterior hypothalamic nucleus (13.0 +/- 2.1 fmol/mg), but these were not significantly different from the low levels in the medial amygdala (4.5 +/- 1.2 fmol/mg) and in the dorsomedial nucleus of the hypothalamus (5.4 +/- 1.1 fmol/mg) of EB-treated females. However, EB caused a significant induction over baseline levels not only in the arcuate-median eminence, periventricular area, and medial preoptic area, but also in the ventromedial nucleus of the hypothalamus and the anterior hypothalamic nucleus. EB did not increase CPRs in the medial amygdala or the dorsomedial nucleus of the hypothalamus.
- Published
- 1986
43. Cytoplasmic progestin receptors in female Guinea Pig brain and their relationship to refractoriness in expression of female sexual behavior
- Author
-
Harvey H. Feder and Jeffrey D. Blaustein
- Subjects
medicine.medical_specialty ,medicine.drug_class ,Guinea Pigs ,Hypothalamus ,Stimulation ,Midbrain ,Guinea pig ,Sexual Behavior, Animal ,chemistry.chemical_compound ,Mesencephalon ,Internal medicine ,medicine ,Animals ,Castration ,Receptor ,Molecular Biology ,Progesterone ,Dose-Response Relationship, Drug ,Estradiol ,General Neuroscience ,Brain ,Lordosis behavior ,Preoptic Area ,Endocrinology ,chemistry ,Ovariectomized rat ,Estradiol benzoate ,Female ,Septum Pellucidum ,Neurology (clinical) ,Receptors, Progesterone ,Progestin ,hormones, hormone substitutes, and hormone antagonists ,Developmental Biology - Abstract
Summary Cytoplasmic progestin receptors were assayed in the hypothalamus-preoptic area-septum and midbrain of ovariectomized guinea pigs given sequential treatment with estradiol benzoate and progesterone. As little as 50 μg of progesterone injected 40 h after estradiol benzoate caused a failure to display lordosis in response to a second progesterone injection 24 h after the first. Both 50 μg and 500 μg of progesterone decreased the concentration of cytoplasmic progestin receptors 24 h later in hypothalamus-preoptic area-septum and midbrain in estrogen-primed, ovariectomized guinea pigs. Therefore, progesterone injections that caused behavioral refractoriness to further stimulation by progesterone also decreased the concentration of availabke cytoplasmic progestin receptors. When progesterone was administered concurrently with 1.6 μg of estradiol benzoate, 500 μg, but not 100 μg suppressed behavioral responsiveness to a second progesterone injection 40 h later. The high dose, but not the low dose, also decreased the concentration of available cytoplasmic progestin receptors 40 h later in both the hypothalamus-preoptic area-septum and midbrain. These findings are consistent with the notion that a decrease in brain progestin receptor concentration is one of the subcellular mechanisms involved in failure of a second dose of progesterone to facilitate lordosis behavior in estrogen-primed animals exposed to a first dose of progesterone 24–40 h earlier.
- Published
- 1979
44. Estradiol and progesterone influencel-5-hydroxytryptophan-induced myoclonus in male guinea pigs: Sex differences in serotonin-steroid interactions
- Author
-
Harvey H. Feder and Lynn H. O'Connor
- Subjects
Male ,Myoclonus ,Serotonin ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,medicine.medical_treatment ,Guinea Pigs ,Biology ,Synaptic Transmission ,Steroid ,5-Hydroxytryptophan ,Sexual Behavior, Animal ,chemistry.chemical_compound ,Internal medicine ,medicine ,Animals ,Drug Interactions ,Molecular Biology ,Progesterone ,Sex Characteristics ,Estradiol ,General Neuroscience ,Reproductive behavior ,nervous system diseases ,Castration ,Endocrinology ,chemistry ,Androgens ,Estradiol benzoate ,Progesterone treatment ,Female ,Neurology (clinical) ,medicine.symptom ,Developmental Biology - Abstract
The effects of castration in males and sex differences in the effects of estradiol and progesterone on l -5-hydroxytryptophan ( l -5-HTP)-induced myoclonus in guinea pigs were examined. Castration had no effect on l -5-HTP-induced myoclonus in males. There were sex differences in sensitivity to l -5-HTP. In the absence of steroids, l -5-HTP-induced myoclonus was higher in gonadectomized males than females. A low dose of estradiol benzoate (EB; 3.5 μg) given 46 h before l -5-HTP (100 mg/kg) enhanced myoclonus in gonadectomized females but not males. However, at a higher dose of EB (10 μg) and a lower dose of l -5-HTP (80 mg/kg), myoclonic responding was enhanced in males. These findings indicate that estradiol has a similar effect on l -5-HTP-induced myoclonus in males and females, but do not rule out the possibility of sex differences in sensitivity to l -5-HTP when both sexes are given estradiol priming. When l -5-HTP was given 6 h after 0.5 mg progesterone in estradiol-primed males, myoclonus was enhanced. Progesterone treatment reverses the facilitative effect of EB on l -5-HTP-induced myoclonus in females. Therefore, progesterone has opposite effects on l -5-HTP-induced myoclonus in males and females. These findings were discussed with respect to the interaction of steroids and 5-HT transmission in the regulation of steroid-dependent reproductive behavior.
- Published
- 1985
45. Sex Steroids and Afferent Input: Their Roles in Brain Sexual Differentiation
- Author
-
Harvey H. Feder and Carlos Beyer
- Subjects
Male ,Aging ,medicine.medical_specialty ,Sex Differentiation ,Dendritic spine ,Sexual differentiation ,Physiology ,medicine.drug_class ,Neural substrate ,Central nervous system ,Brain ,Biology ,Androgen ,Gonadotropin secretion ,Sexual dimorphism ,Endocrinology ,medicine.anatomical_structure ,Estrogen ,Internal medicine ,medicine ,Animals ,Female ,Steroids ,Gonadal Steroid Hormones - Abstract
Sexually dimorphic patterns of sexual behavior and gonadotropin secretion in adult rodents arise as a result of the presence or absence of androgen (or androgen metabolites, primarily estrogen) during the perinatal period (13, 14, 16, 22-24, 44, 51, 70). Central nervous system (CNS) regions underlying control of these reproductive processes show sex differences in various morphological parameters such as size of nuclei in neuronal groups, number of neurons, neuronal volume, extent of dendritic extension and branching, number of dendritic spines, morphology and localization of synapses, and cell nuclear volume and structure (5, 14, 23, 70). Moreover, there are reports of sex differences in the pattern of connectivity between various limbic regions related to reproductive functions (15, 63). The importance of hormones in directing or organizing brain sexual dimorphism has been illustrated con vincingly by two types of experiments: (a) Castration of genetic (XY) males during perinatal life demasculinizes and feminizes the neural substrate for sexual behavior and feminizes the brain-pituitary axis destined to mediate adult patterns of gonadotropin secretion, and (b) injection of androgen into
- Published
- 1987
46. α1-Noradrenergic regulation of hypothalamic progestin receptors and guinea pig lordosis behavior
- Author
-
Harvey H. Feder and Bruce Nock
- Subjects
medicine.medical_specialty ,Phenoxybenzamine ,Guinea Pigs ,Posture ,Hypothalamus ,Alpha (ethology) ,Clonidine ,Norepinephrine ,Sexual Behavior, Animal ,chemistry.chemical_compound ,Internal medicine ,medicine ,Prazosin ,Animals ,Receptor ,Molecular Biology ,Brain Mapping ,Estradiol ,Chemistry ,General Neuroscience ,Lordosis behavior ,Preoptic area ,Endocrinology ,Estradiol benzoate ,Female ,Neurology (clinical) ,Receptors, Progesterone ,hormones, hormone substitutes, and hormone antagonists ,Developmental Biology ,medicine.drug - Abstract
Experiments were conducted to determine whether alpha 1- or alpha 2-receptors mediate noradrenergic (NA) regulation of guinea pig lordosis behavior and hypothalamic progestin receptors. When infused into a lateral cerebroventricle at a dose that inhibits lordosis and that decreases the concentration of estradiol-inducible hypothalamic progestin receptors, phenoxybenzamine decreased binding of the alpha 1-ligand [3H]WB4101 but not the alpha 2-ligand [3H]clonidine to brain membranes. Thus, under the conditions used, phenoxybenzamine appears to block alpha 1-receptors with little or no effect on alpha 2-receptors. Experiments with the selective alpha 1-antagonist prazosin also indicated alpha 1-receptor regulation of lordosis and hypothalamic progestin receptors. Prazosin inhibited lordosis induced by estradiol benzoate (EB) plus progesterone and by EB + clonidine and decreased the concentration of cytoplasmic progestin receptors in hypothalamus (but not in preoptic area or frontal cortex) of EB-primed females. The inhibition of lordosis is apparently not due to some unknown side effect of prazosin because pretreatment with a high dose of clonidine attenuated the inhibition. The possibility that a causal relationship exists between effects of alpha 1-NA transmission on hypothalamic progestin receptors and lordosis was discussed. Also, because effects of NA transmission on hypothalamic progestin receptors are dependent on prior treatment with EB, it was suggested that NA transmission might influence estradiol action in addition to progestin action in hypothalamic cells.
- Published
- 1984
47. Alpha-1- and Alpha-2-Noradrenergic Receptors Modulate Lordosis Behavior in Female Guinea Pigs
- Author
-
Patricia A. Vincent and Harvey H. Feder
- Subjects
medicine.medical_specialty ,Lordosis ,Ovariectomy ,Endocrinology, Diabetes and Metabolism ,Guinea Pigs ,Alpha (ethology) ,Stimulation ,Biology ,Methoxamine ,Guinea pig ,Phenylephrine ,Sexual Behavior, Animal ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Endocrinology ,Quinoxalines ,Internal medicine ,medicine ,Animals ,Endocrine and Autonomic Systems ,Lordosis behavior ,medicine.disease ,Receptors, Adrenergic ,chemistry ,Brimonidine Tartrate ,Ovariectomized rat ,Estradiol benzoate ,Female ,Alpha-2 adrenergic receptor - Abstract
Modulation of lordosis behavior by stimulation of noradrenergic receptor subtypes was examined in ovariectomized, estradiol benzoate (10 micrograms)-primed guinea pigs. In the first experiment, subcutaneous administration of the alpha-2-noradrenergic agonist, UK-14,304 (0.01, 0.5, or 1.0 mg/kg, Pfizer Central Research), produced a significant increase in lordosis behavior when these animals were compared with estrogen-primed control animals injected with saline. In a second experiment, estrogen-primed animals were injected with the alpha-1-noradrenergic agonist methoxamine (0.5 mg/kg, s.c.), UK-14,304 (0.5 mg/kg, s.c.), or both drugs given together. Methoxamine or UK-14,304 administered alone facilitated lordosis in fewer than 50% of animals (17 and 39%, respectively). However, when both drugs were given together, 76% of the animals became sexually receptive. A third experiment showed that lordosis behavior facilitated by UK-14,304 could be attenuated by the administration of the alpha-2-noradrenergic antagonist idazoxan (2.5 mg/kg, s.c.). Only 29% of sexually receptive animals (i.e. those animals primed with estradiol benzoate plus UK-14,304) continued to show lordosis after they received idazoxan. The results obtained from these and previously reported experiments suggest that both alpha-1- and alpha-2-noradrenergic receptors are involved in the regulation of lordosis behavior in the guinea pig.
- Published
- 1988
48. Noradrenergic regulation of α1-receptors during the postnatal development of the guinea pig
- Author
-
Bruce Nock, Donald L. Allen, Allan E. Johnson, Harvey H. Feder, Kenneth J. Renner, and Victoria N. Luine
- Subjects
medicine.medical_specialty ,Guinea Pigs ,Hypothalamus ,Stimulation ,Biology ,Guinea pig ,Hydroxydopamines ,Norepinephrine ,chemistry.chemical_compound ,Developmental Neuroscience ,Internal medicine ,medicine ,Animals ,Oxidopamine ,Neurotransmitter ,Brain Chemistry ,Cerebral Cortex ,Brain ,Prazosin ,Receptors, Adrenergic, alpha ,Preoptic Area ,Preoptic area ,Endocrinology ,chemistry ,Catecholamine ,Female ,Developmental Biology ,medicine.drug - Abstract
In guinea pig brain, alpha 1-noradrenergic receptor concentrations undergo region-specific fluctuations during the first weeks of postnatal life. However, the factors involved in the regulation of these receptors have yet to be identified. In this study, the ontogeny of one possible regulatory factor, norepinephrine, was examined in relation to postnatal changes in alpha 1-receptor levels in several different regions of guinea pig brain. Results from these studies showed that while the activity of the noradrenergic system increased throughout the first weeks of postnatal development in each brain area examined, the concentration of alpha 1-receptors decreased in preoptic area and hypothalamus and increased in cortex. In subsequent experiments, the effects of noradrenergic lesions with 6-hydroxydopamine on alpha 1-receptor levels were assessed to examine the possibility that alpha 1-receptors are differentially sensitive to noradrenergic stimulation in cortex and preoptic area/hypothalamus in immature guinea pigs. Noradrenergic lesions which reduced norepinephrine levels by 87-94% resulted in significant elevations in alpha 1-receptors in all regions examined. These results are discussed with reference to the anatomical distribution of alpha 1-receptors and their regulation by norepinephrine.
- Published
- 1987
49. The comparative potency of various steroids to complete the priming process for lordosis in guinea pigs
- Author
-
William A. Walker and Harvey H. Feder
- Subjects
medicine.medical_specialty ,Hydrocortisone ,Lordosis ,Estrone ,Guinea Pigs ,Diethylstilbestrol ,Sexual Behavior, Animal ,Behavioral Neuroscience ,chemistry.chemical_compound ,Endocrinology ,Estradiol Congeners ,Internal medicine ,medicine ,Animals ,Testosterone ,Progesterone ,Dose-Response Relationship, Drug ,Estradiol ,Estriol ,Endocrine and Autonomic Systems ,medicine.disease ,Lordosis behavior ,chemistry ,Ovariectomized rat ,Estradiol benzoate ,Female ,Steroids ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
Ovariectomized adult guinea pigs were treated with a regimen of estradiol benzoate (0.2 μg/animal estradiol benzoate at hr 0 and 19) that was shown to be minimally effective for the induction of lordosis. They were then treated with 10, 20, or 80 mg of enclomiphene, 5, 20, 40, or 100 μg of estradiol, or testosterone, cortisol, estrone, estriol, diethylstilbestrol, catechol estradiol, or catechol estrone (all at a dose equivalent to 5 μg of estradiol) at hr 28. At hr 39 all females were given 0.5 mg progesterone, and subsequently tested for lordosis behavior. Of the various agents injected at hr 28 only estradiol (at all doses given), estrone, estriol, and diethylstilbestrol were effective in supporting display of lordosis behavior. The results indicate that the antiestrogen enclomiphene, the catechol estrogens, and at least some C19 and C21 steroids are weaker than E2 or ineffective in facilitating lordosis behavior when given late in the priming period. Because previous work had shown that enclomiphene has partial estrogenic effects on lordosis behavior when administered early in the priming period (i.e., at hr 0, 19), it is suggested the early and late phases of the priming process induced by E2 entail qualitatively different neural processes.
- Published
- 1979
50. Estradiol and progesterone influence a serotonin mediated behavioral syndrome (myoclonus) in female guinea pigs: Comparison with steroid effects on reproductive behavior
- Author
-
Harvey H. Feder and Lynn H. O'Connor
- Subjects
Myoclonus ,Serotonin ,medicine.medical_specialty ,Lordosis ,Guinea Pigs ,Models, Neurological ,Posture ,Biology ,Inhibitory postsynaptic potential ,Serotonergic ,5-Hydroxytryptophan ,Guinea pig ,Sexual Behavior, Animal ,chemistry.chemical_compound ,Internal medicine ,medicine ,Animals ,Drug Interactions ,Receptor ,Molecular Biology ,Progesterone ,Estradiol ,General Neuroscience ,medicine.disease ,Endocrinology ,chemistry ,Estradiol benzoate ,Female ,Neurology (clinical) ,medicine.symptom ,Receptors, Progesterone ,Developmental Biology - Abstract
l -5-hydroxytryptophan ( l -5-HTP)-induced myoclonus was used as a behavioral index of central serotonergic activity. Estradiol benzoate (EB) and progesterone (P) influenced the induction of myoclonus by l -5-HTP. When l -5-HTP was injected 46 h after EB, myoclonus was enhanced. P blocked this effect on EB when 100 or 125 mg/kg l -5-HTP (but not 80 mg/kg) was given 6 h after P in EB-primed animals. When l -5-HTP was given 3 or 11–15 h after P in EB-primed animals, there was no inhibitory effect of P on myoclonus. In fact, at the lowest dose (80 mg/kg), l -5-HTP increased myoclonus when given 3 h after P in EB-primed animals. The inhibitory effects of P in EB-primed females on myoclonus were temporally correlated with the display of lordosis, suggesting that the neural progestin receptor mechanisms that have been proposed to mediate P effects on lordosis are also involved in the inhibitory effects of P on myoclonus.
- Published
- 1984
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