129 results on '"Feder HH"'
Search Results
2. Rho overexpression leads to mitosis-associated detachment of cells from epithelial sheets: a link to the mechanism of cancer dissemination.
- Author
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Vasiliev JM, Omelchenko T, Gelfand IM, Feder HH, and Bonder EM
- Subjects
- Animals, Cells, Cultured, Epithelial Cells cytology, Humans, Neoplasms pathology, Rats, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins metabolism, Spindle Apparatus metabolism, rhoA GTP-Binding Protein genetics, Cell Adhesion physiology, Epithelial Cells metabolism, Mitosis physiology, Neoplasms metabolism, Signal Transduction physiology, rhoA GTP-Binding Protein metabolism
- Abstract
Dissemination of neoplastic cells from the primary tumor (invasion and metastasis) is a fundamentally dangerous step in multistage carcinogenesis. Recent evidence suggests that Rho GTPase-mediated signaling is linked to dissemination of cells from several different types of human tumors. The Rho family of proteins is typically associated with the regulation of cytoskeletal activity, including actin assembly, microtubule dynamics, and myosin II-dependent contractility of the actin-rich cortex. We examined the effect of overexpression of constitutively active RhoA on islands and monolayers of epithelial cells. Although newly plated cells initially formed small spread islands, there was also a significant population of cells that detached from the substrate, floated in the medium, and then could reattach to the substrate to form new colonies. Detachment of cells from transfected epithelial islands or monolayers occurred in correlation to the plane of cytokinesis after misorientation of the mitotic spindle axis. We suggest that these alterations result from Rho-induced increase of contractility of the cortex of dividing cells, which, during cytokinesis, produces a cell that has budded out of an existing layer of cells. Cell division-mediated detachment of cells from tissue structures may be an important mechanism of tumor dissemination and metastasis.
- Published
- 2004
- Full Text
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3. Rho-dependent formation of epithelial "leader" cells during wound healing.
- Author
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Omelchenko T, Vasiliev JM, Gelfand IM, Feder HH, and Bonder EM
- Subjects
- Amides pharmacology, Animals, Cell Movement, Enzyme Inhibitors pharmacology, Microscopy, Fluorescence, Pyridines pharmacology, Rats, Wound Healing physiology, rhoA GTP-Binding Protein physiology
- Abstract
The motile behavior of epithelial cells located at the edge of a large wound in a monolayer of cultured cells was analyzed. The initial cellular response is alignment of the edge with an accompanying formation of tangential marginal actin bundles within individual cells positioned along the wound edge. Later, coherent out-growths of cell masses occur by the formation of special "leader" cells at the tops of outgrowths and "follower" cells along the sides. Leader cells exhibit profound cytoskeletal reorganization, including disassembly of marginal bundles, the realignment of actin filament bundles, and penetration of microtubules into highly active lamellae. Additionally, cell-cell contacts acquire radial geometry indicative of increased contractile tension. Interestingly, leader cells acquire a cytoskeletal organization and motility typical of fibroblasts. IAR-2 cultures stably transfected with a dominant-negative mutant of RhoA or treated with Rho-kinase inhibitor Y-27632 transformed most edge cells into leader-like cells. Alternatively, transfection of cells with constitutively active RhoA suppressed formation of leaders. Thus, expansion of the epithelial sheet involves functional differentiation into two distinct types of edge cells. The transition between these two patterns is controlled by Rho activity, which in turn controls the dynamic distribution and activity of actin filament bundles, myosin II, and microtubules.
- Published
- 2003
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4. Mechanisms of polarization of the shape of fibroblasts and epitheliocytes: Separation of the roles of microtubules and Rho-dependent actin-myosin contractility.
- Author
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Omelchenko T, Vasiliev JM, Gelfand IM, Feder HH, and Bonder EM
- Subjects
- Amides pharmacology, Animals, Cell Line, Cell Polarity drug effects, Cell Size drug effects, Enzyme Inhibitors pharmacology, Epithelial Cells cytology, Epithelial Cells drug effects, Fibroblasts cytology, Fibroblasts drug effects, Intracellular Signaling Peptides and Proteins, Microtubules drug effects, Nocodazole pharmacology, Pyridines pharmacology, Rats, rho-Associated Kinases, Actins metabolism, Microtubules physiology, Myosins metabolism, Protein Serine-Threonine Kinases antagonists & inhibitors
- Abstract
Cultured fibroblasts possess a characteristic polarized phenotype manifested by an elongate cell body with an anterior lamella whose cell edge is divided into protrusion-forming and inactive zones. Disruption of the fibroblast microtubule cytoskeleton leads to an increase in Rho-dependent acto-myosin contractile activity and concomitant loss of structural polarity. The functional relationship of myosin-driven contractile activity to loss of fibroblast anterior-posterior polarity is unknown. To dissect the roles of microtubule assembly and of Rho-dependent contractility on structural polarization of cells, polarized fibroblasts and nonpolarized epitheliocytes were treated with the microtubule-depolymerizing drug, nocodazole, and/or the Rho kinase inhibitor, Y-27632. Fibroblasts incubated with Y-27632 increased their degree of polarization by developing a highly elongate cell body with multiple narrow processes extended from the edges of the cell. Treatment of fibroblasts with nocodazole, alone or in combination with Rho kinase inhibitor, produced discoid or polygonal cells having broad, flattened lamellae that did not form long lamellar extensions. Single cultured epitheliocytes of the IAR-2 line do not display anterior-posterior polarization. When treated with Y-27632, the cells acquired a polarized, elongate shape with narrow protrusions and wide lamellas. Nocodazole alone or in combination with Y-27632 did not change the discoid shape of epitheliocytes, however treatment with Y-27632 produced thinning of the lamellar cytoplasm. We conclude that microtubules provide the necessary framework for polarization of fibroblasts and epitheliocytes, whereas Rho-regulated contractility modulates the degree of polarization of fibroblasts and completely inhibits polarization in epitheliocytes.
- Published
- 2002
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5. Myosin-dependent contractile activity of the actin cytoskeleton modulates the spatial organization of cell-cell contacts in cultured epitheliocytes.
- Author
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Krendel M, Gloushankova NA, Bonder EM, Feder HH, Vasiliev JM, and Gelfand IM
- Subjects
- Actins drug effects, Animals, Cadherins metabolism, Cells, Cultured, Cytoskeleton drug effects, Epithelial Cells physiology, Liver cytology, Microscopy, Confocal, Microtubules metabolism, Nocodazole pharmacology, Rats, Tetradecanoylphorbol Acetate pharmacology, Wound Healing, Actins physiology, Cell Communication drug effects, Cytoskeleton physiology, Epithelial Cells cytology, Myosins physiology
- Abstract
The spatial organization of cell-cell adherens junctions is distinct in cultured cells from two different tissue types, specifically, epitheliocytes and fibroblasts. In epitheliocytes, contacts are localized tangentially, along contacting cell edges and in association with circumferential actin bundles. Contacts between fibroblasts are radially oriented; that is, they are perpendicular to the overlapping edges of the cells and are associated with straight bundles of actin filaments. In the present study, we establish that the spatial organization of cell-cell contacts in the epithelial cell line IAR-2 can be converted from the typical tangential pattern to the radial pattern observed in fibroblasts. This transition can be induced by treatment with two agents, phorbol 12-myristate 13-acetate and nocodazole, which have different modes of action. Inhibition of myosin contractility reverses tangential-to-radial conversion of cell-cell contacts. These data suggest that formation of radially aligned contacts depends on modulation of contractility within the actin cytoskeleton through the myosin motor protein. The results open the possibility that modulation of the spatial organization of cell-cell contacts may play important roles in regulating organization and physiological functions of epithelial tissues.
- Published
- 1999
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6. Dynamics of contacts between lamellae of fibroblasts: essential role of the actin cytoskeleton.
- Author
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Gloushankova NA, Krendel MF, Alieva NO, Bonder EM, Feder HH, Vasiliev JM, and Gelfand IM
- Subjects
- Animals, Cadherins analysis, Cell Line, Cytoskeletal Proteins analysis, Diacetyl analogs & derivatives, Diacetyl pharmacology, Fibroblasts cytology, Fibroblasts physiology, Humans, Intercellular Junctions ultrastructure, Myosins antagonists & inhibitors, Rats, beta Catenin, Actins physiology, Cell Communication physiology, Cytoskeleton physiology, Intercellular Junctions physiology, Myosins physiology, Trans-Activators
- Abstract
We investigated actin cytoskeletal and adhesion molecule dynamics during collisions of leading lamellae of nontransformed and oncogene-transformed fibroblasts. By using real-time video microscopy, it was found that during lamellar collision there was considerable overlapping of leading lamellae followed by subsequent retraction. Overlapping of nontransformed fibroblasts was accompanied by formation of beta-catenin-positive contact structures organized into strands oriented parallel to the long axis of the cell that were associated with bundles of actin filaments. Maintenance of such cell-cell contact structures critically depended on the contractility of actin cytoskeleton, as inhibition of contractility with serum-free medium or 2,3-butanedione 2-monoxime (BDM) resulted in loss of strand formation. Strand formation was recovered when cells in serum-free medium were incubated with the microtubule inhibitor nocodazole, which is known to increase contractility. Oncogene-transformed fibroblasts reacted to collisions with responses similar to nontransformed fibroblasts but did not develop well-organized cell-cell contacts. A model is presented to describe how differences in the organization of the actin cytoskeleton could account for the structurally distinct responses to cell-cell contact by polarized fibroblastic cells versus nonpolarized epithelial cells.
- Published
- 1998
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7. Cell-cell contact changes the dynamics of lamellar activity in nontransformed epitheliocytes but not in their ras-transformed descendants.
- Author
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Gloushankova NA, Alieva NA, Krendel MF, Bonder EM, Feder HH, Vasiliev JM, and Gelfand IM
- Subjects
- Actins analysis, Animals, Cell Adhesion Molecules analysis, Cell Line, Cell Line, Transformed, Epithelial Cells, Epithelium chemistry, Rats, Vinculin analysis, ras Proteins physiology, Cell Adhesion physiology, Cell Communication physiology, Cytoskeleton physiology, Pseudopodia physiology
- Abstract
We investigated the structural and functional alterations of active lamellae during initial cell-cell collision and establishment of cell-cell contacts in wounded cultures of nontransformed rat epitheliocytes (IAR-2 line) and their ras-transformed descendants (C4 line). Typically, the leading edges of nontransformed cells formed multiple transient contacts followed by establishment of small, stable contacts that would undergo lateral expansion. Formation and expansion of the contact area was accompanied by accumulation of the cell-cell adhesion molecules E-cadherin, beta-catenin, and plakoglobin. During lateral expansion, the circumferential bundles of actin filaments, characteristic of IAR-2 cells, disassembled at the site of stable contact forming a concave arc-like actin bundle between adjacent cells at the expanding edge. Pseudopodial activity was completely inhibited in the contact zone and partially inhibited at the free lamellar edges adjacent to the zone of contact. Con A-coated beads on the plasma membrane at the zone of contact stopped undergoing centripetal transport but now moved along the cell-cell boundary. On the other hand, ras-transformed cells developed overlapping lamellae and exhibited no detectable change in activity of lamellae, localization of adhesion molecules, and organization of the actin cytoskeleton. We propose that contact-induced reorganization of cell surface adhesion molecules and the underlying cortical cytoskeleton leads to development of lateral traction that may be an essential element in inducing expansion of the contact and in inhibiting local pseudopodial activity.
- Published
- 1997
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8. Dynamics of active lamellae in cultured epithelial cells: effects of expression of exogenous N-ras oncogene.
- Author
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Gloushankova NA, Krendel MF, Sirotkin VA, Bonder EM, Feder HH, Vasiliev JM, and Gelfand IM
- Subjects
- Animals, Cell Line, Cells, Cultured, Concanavalin A, Cytoskeleton physiology, Epithelium drug effects, Epithelium ultrastructure, Gene Expression Regulation, Liver drug effects, Microtubules physiology, Nocodazole pharmacology, Pseudopodia physiology, Pseudopodia ultrastructure, Rats, Cell Transformation, Neoplastic genetics, Cytoskeleton ultrastructure, Genes, ras, Liver ultrastructure, Microtubules ultrastructure
- Abstract
We examined the functional consequences of cellular transformation of rat IAR-2 epithelial cells, by a mutant N-ras oncogene, on the dynamics of active lamellae, structures that play an important role in cell motility, adhesion, and surface-receptor capping. Lamellar activity was assessed by measuring the rate of outer-edge pseudopodial activity and by analyzing the motility of Con A-coated beads placed on lamellar surfaces with optical tweezers. Although transformation dramatically affected the shape and size of active cellular lamellae, there was little detectable effect on either pseudopodial activity or bead movement. To investigate the potential relationship between functional lamellar activity and the microtubule cytoskeleton, lamellar activity was examined in nontransformed and transformed cells treated with the microtubule-disrupting drug nocodazole. In the absence of microtubules, transformed cells were less polarized and possessed decreased rates of pseudopodial and bead motility. On the basis of these observations, it is suggested that ras-induced transformation of epithelial cells consists of two cytoskeletal modifications: overall diminished actin cytoskeletal dynamics in lamellae and reorganization of the microtubule cytoskeleton that directs pseudopodial activity to smaller polarized lamellae.
- Published
- 1995
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9. Role of the microtubular system in morphological organization of normal and oncogene-transfected epithelial cells.
- Author
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Gloushankova NA, Lyubimova AV, Tint IS, Feder HH, Vasiliev JM, and Gelfand IM
- Subjects
- Animals, Cell Polarity, Cells, Cultured, Cytoskeleton ultrastructure, Demecolcine pharmacology, Epithelium ultrastructure, Genes, ras, In Vitro Techniques, Paclitaxel pharmacology, Rats, Transfection, Video Recording, Cell Transformation, Neoplastic ultrastructure, Microtubules physiology
- Abstract
To understand better the role of the microtubular system in the development and maintenance of morphological organization of nonpolarized and polarized cells of the same origin we examined the effects of two microtubule-specific drugs, colcemid and taxol, on discoid cultured epithelial rat cells of the IAR-2 line and on polarized cells obtained from this line by transfection of mutated N-ras oncogene; morphometric, immunomorphologic, and videomicroscopic methods were used. Depolymerization of microtubules by colcemid did not cause major changes in the discoid shape of IAR cells but altered organization of actin cortex; in particular, it led to disappearance of circumferential bundle of actin microfilaments. Taxol reorganized the normal network of microtubules radiating from the perinuclear centers into numerous arrays of short microtubules not associated with any centers. Taxol-treated cells had wider circumferential bundles of microfilaments than control cells and morphometric analysis showed that their contours were closer to geometric circle than those of control or of colcemid-treated cells. These data show that function of the microtubular system is essential for maintenance of the characteristic morphological organization of discoid cells; we propose to name this function "contra-polarization." Contra-polarization is not prevented and is even promoted by taxol; this result suggests that a decentralized system of microtubules is sufficient for this function. In contrast, maintenance of polarized morphology of IAR-2 cells transfected by the N-ras oncogene is inhibited not only by colcemid but also by taxol and thus requires the presence of a normal centralized microtubular system.
- Published
- 1994
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10. 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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Malik KF, Morrell JI, and Feder HH
- Subjects
- Adrenergic alpha-Agonists pharmacology, Animals, Brimonidine Tartrate, Estradiol pharmacology, Female, Guinea Pigs, Progesterone pharmacology, Quinoxalines pharmacology, Yohimbine pharmacology, Hypothalamus, Middle drug effects, Posture, Preoptic Area drug effects, Receptors, Adrenergic, alpha-2 drug effects, Sexual Behavior, Animal drug effects, Synaptic Transmission drug effects
- 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); P < 0.005). 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; P < 0.025). 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; P < 0.05). 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
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11. Estrogen receptor immunostaining in the preoptic area and medial basal hypothalamus of estradiol benzoate- and prazosin-treated female guinea-pigs.
- Author
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Malik KF, Feder HH, and Morrell JI
- Subjects
- Animals, Antibodies, Monoclonal, Female, Guinea Pigs, Hypothalamus, Middle drug effects, Immunohistochemistry, Ovariectomy, Preoptic Area drug effects, Estradiol pharmacology, Hypothalamus, Middle metabolism, Prazosin pharmacology, Preoptic Area metabolism, Receptors, Estrogen metabolism
- 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.
- Published
- 1993
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12. Effects of clonidine and phentolamine infused into the medial preoptic area and medial basal hypothalamus of the guinea pig.
- Author
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Malik KF, Morrell JI, and Feder HH
- Subjects
- Animals, Female, Guinea Pigs, Hypothalamus, Anterior drug effects, Infusions, Parenteral, Adrenergic alpha-Agonists administration & dosage, Clonidine administration & dosage, Hypothalamus, Middle drug effects, Lordosis physiopathology, Phentolamine administration & dosage, Preoptic Area drug effects
- 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 (p < 0.05) 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 p < 0.001). 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 (p < 0.05). 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; p < 0.01). 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%; p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1993
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13. 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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Thornton JE, Roy M, Vincent P, Goy RW, McEwen BS, and Feder HH
- Subjects
- Animals, Drug Interactions, Female, Guinea Pigs, Idazoxan, Injections, Male, Ovariectomy, Progesterone pharmacology, Sex Characteristics, Time Factors, Adrenergic alpha-Antagonists pharmacology, Dioxanes pharmacology, Estrogens pharmacology, Lordosis chemically induced
- 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 micrograms/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
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14. Reversible structural alterations of undifferentiated and differentiated human neuroblastoma cells induced by phorbol ester.
- Author
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Tint IS, Bonder EM, Feder HH, Reboulleau CP, Vasiliev JM, and Gelfand IM
- Subjects
- Actins metabolism, Cytoskeleton ultrastructure, Humans, In Vitro Techniques, Neurites ultrastructure, Neurons cytology, Protein Kinase C physiology, Tumor Cells, Cultured, Cell Differentiation drug effects, Neuroblastoma pathology, Tetradecanoylphorbol Acetate pharmacology
- Abstract
Morphological alterations in the structure of undifferentiated and morphologically differentiated human neuroblastoma cells induced by phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, were examined by video microscopy and immunomorphology. In undifferentiated cells, PMA induced the formation of motile actin-rich lamellas and of stable cylindrical processes rich in microtubules. Formation of stable processes resulted either from the collapse of lamellas or the movement of the cell body away from the base of a process. In differentiated cells, PMA induced the rapid extension of small lamellas and subsequent formation of short-lived elongated processes from the lateral edges of neurites. Additionally, growth cones exhibited enhanced modulation in shape after PMA treatment. These reversible reorganizations were similar to the actinoplast-tubuloplast transformations exhibited by PMA-treated fibroblasts. We suggest that actinoplast-tubuloplast reorganizations play essential roles in morphogenesis where stable cytoplasmic extensions are induced by external stimuli. In particular, PMA-induced reorganizations of neural cells in culture may be a model for morphological modulations that occur in nerve tissue.
- Published
- 1992
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15. Excitatory amino acid modulation of lordosis in the rat.
- Author
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McCarthy MM, Curran GH, and Feder HH
- Subjects
- 2-Amino-5-phosphonovalerate administration & dosage, Animals, Female, Hypothalamus, Middle drug effects, Infusions, Parenteral, N-Methylaspartate administration & dosage, Preoptic Area drug effects, Rats, Rats, Inbred Strains, Reference Values, Vocalization, Animal, 2-Amino-5-phosphonovalerate pharmacology, Estradiol pharmacology, Hypothalamus, Middle physiology, N-Methylaspartate pharmacology, Posture, Preoptic Area physiology, Progesterone pharmacology, Sexual Behavior, Animal drug effects
- Abstract
Microinfusion of the excitatory amino acid agonist N-methyl-D-aspartate (NMDA) into the mediobasal hypothalamus (MBH) significantly reduced lordosis in estrogen plus progesterone-treated female rats at 10 min post-infusion with recovery to pretest values by 30 min (P less than .05; Wilcoxon). Microinfusion of the specific NMDA antagonist D,L2-amino-5-phosphonopentoic acid (AP-5) into the same sites was without effect on lordosis responding of fully receptive females. There was also a significant increase in the number of females vocalizing to mounts by males after infusion of NMDA but not after infusion of AP-5 into the MBH. When NMDA was infused into the preoptic area (POA) there was no effect on lordosis responding of full receptive females, but AP-5 infusion resulted in a significant inhibition of lordosis at 10 min post-infusion. There was no difference between groups in percentage of females vocalizing after drug infusion into the POA. These results suggest that increased excitatory amino acid activity in the MBH and decreased excitatory amino acid activity in the POA inhibits lordosis behavior.
- Published
- 1991
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16. GABAergic control of receptivity in the female rat.
- Author
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McCarthy MM, Masters DB, Fiber JM, López-Colomé AM, Beyer C, Komisaruk BR, and Feder HH
- Subjects
- Animals, Cerebral Cortex metabolism, Estradiol pharmacology, Female, Hypothalamus drug effects, Muscimol metabolism, Ovariectomy, Posture, Preoptic Area drug effects, Progesterone pharmacology, Rats, Rats, Inbred Strains, Hypothalamus metabolism, Preoptic Area metabolism, Sexual Behavior, Animal physiology, gamma-Aminobutyric Acid metabolism
- 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
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17. Progestin receptors in the ventromedial nucleus of the hypothalamus and arcuate nucleus-median eminence are decreased by idazoxan.
- Author
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Vincent PA and Feder HH
- Subjects
- Adrenergic alpha-Antagonists pharmacology, Animals, Cytosol metabolism, Female, Guinea Pigs, Idazoxan, Osmolar Concentration, Promegestone metabolism, Tissue Distribution, Arcuate Nucleus of Hypothalamus metabolism, Dioxanes pharmacology, Median Eminence metabolism, Receptors, Progesterone metabolism, Ventromedial Hypothalamic Nucleus metabolism
- 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
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18. Increased GABAergic transmission in medial hypothalamus facilitates lordosis but has the opposite effect in preoptic area.
- Author
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McCarthy MM, Malik KF, and Feder HH
- Subjects
- Animals, Bicuculline pharmacology, Female, Hypothalamus, Middle drug effects, Muscimol pharmacology, Posture, Preoptic Area drug effects, Rats, Rats, Inbred Strains, Hypothalamus, Middle physiology, Preoptic Area physiology, Sexual Behavior, Animal drug effects, gamma-Aminobutyric Acid physiology
- Abstract
The role of gamma-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
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19. Development of steroid-receptor systems in guinea pig brain. II. Cytoplasmic progestin receptors.
- Author
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Ryer HI and Feder HH
- Subjects
- Aging, Animals, Brain growth & development, Castration, Estradiol pharmacology, Female, Guinea Pigs, Male, Receptors, Progesterone drug effects, Sex Characteristics, Animals, Newborn growth & development, Brain metabolism, Cytoplasm metabolism, Receptors, Progesterone analysis, Receptors, Steroid physiology
- Abstract
The development of the cytoplasmic progestin receptor (CPR) system in male and female guinea pigs was examined to determine if insensitivity to the lordosis promoting activity of estrogen-progestin treatment in adult males and neonatal guinea pigs is correlated with alterations in this receptor system. Gonadectomized neonatal (4-6 days old) and adult (50-65 days old) guinea pigs of both sexes were injected with estradiol benzoate (EB) and killed 40 h later. CPRs were measured in the hypothalamus (HYPO), preoptic area (POA) and cortex ( CORT ). Neonatal brain contained both high (Kd congruent to 0.1 nM) and low (Kd greater than 10 nM) affinity binders for [3H]R5020 similar to those found in adult brain. In the absence of EB-priming the concentration of CPR in HYPO, POA and CORT was lower in neonatal animals than adults. In both males and females, neither a low (1.6 micrograms) nor a high (10 micrograms) dose of EB resulted in a concentration of estrogen inducible CPR in neonatal HYPO greater than that found in adult HYPO after 1.6 micrograms EB. Even after treatment with 50 micrograms EB the concentration of CPR in neonatal female HYPO was not different from adult female HYPO after 1.6 micrograms EB. In neonatal POA, 10 micrograms EB resulted in a concentration of CPR greater than that found in adult POA after 1.6 micrograms EB. Finally, there was a sex difference in the concentration of estrogen inducible CPR in HYPO (female greater than male) but not POA of adult guinea pigs. No sex difference in CPR concentration was found in any neonatal brain area.
- Published
- 1984
- Full Text
- View/download PDF
20. Hormones modulate the concentration of cytoplasmic progestin receptors in the brain of male ring doves (Streptopelia risoria).
- Author
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Balthazart J, Blaustein JD, Cheng MF, and Feder HH
- Subjects
- Animals, Binding, Competitive, Brain drug effects, Castration, Cytoplasm metabolism, Dihydrotestosterone pharmacology, Gonadal Steroid Hormones pharmacology, Male, Promegestone metabolism, Receptors, Progesterone drug effects, Brain metabolism, Columbidae metabolism, Progestins, Receptors, Progesterone metabolism
- Abstract
A cytoplasmic progestin receptor has been characterized in the brain of castrated ring doves using an in-vitro assay that measures the binding of a synthetic progestin, [3H]17 alpha,21-dimethyl-19-nor-pregna-4,9-diene-3,20-dione(promegestone; R5020). The affinity of the receptor was similar in both the hyperstriatum and the hypothalamus (Kd approximately equal to 4 X 10(-10) mol/l). Its concentration was higher in the anterior hypothalamus-preoptic area (63 +/- 4 fmol/mg (S.E.M.) protein) than in other brain regions (posterior hypothalamus, 33 +/- 5; hyperstriatum, 28 +/- 3; midbrain, 17 +/- 4 fmol/mg protein; n = 7). Progesterone and R5020 competed well for binding but oestradiol and 5 beta-dihydrotestosterone did not. Corticosterone and, to a lesser extent, testosterone and 5 alpha-dihydrotestosterone completed for binding but much higher concentrations were required than for progestins. Injections of testosterone (200 micrograms testosterone propionate daily for 7 days) significantly increased the concentration of progestin receptors in the anterior and posterior hypothalamus without having any significant effect on other brain areas. Shorter treatment, lasting for 2 days, with testosterone propionate (200 micrograms daily), 5 alpha-dihydrotestosterone (200 micrograms daily) or oestradiol benzoate (50 micrograms daily) did not always cause this increase but seven injections of oestradiol benzoate (50 micrograms daily for 7 days) were even more effective than seven injections of testosterone propionate (200 micrograms daily for 7 days). These data suggested that the sensitivity to progesterone of the brain of the bird changes as a consequence of increases in the level of testosterone in the circulation.
- Published
- 1980
- Full Text
- View/download PDF
21. Oestrogen-progestin regulation of female sexual behavior in guinea pigs.
- Author
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Feder HH, Blaustein JD, and Nock BL
- Subjects
- Animals, Female, Guinea Pigs, Hypothalamus physiology, Mesencephalon physiology, Posture, Preoptic Area physiology, Promegestone metabolism, Estradiol pharmacology, Receptors, Progesterone metabolism, Sexual Behavior, Animal drug effects
- Published
- 1979
- Full Text
- View/download PDF
22. Estrogen induction of progestin receptors in microdissected hypothalamic and limbic nuclei of female guinea pigs.
- Author
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Thornton JE, Nock B, McEwen BS, and Feder HH
- Subjects
- Animals, Cytosol analysis, Estradiol pharmacology, Female, Guinea Pigs, Hypothalamus metabolism, Kinetics, Limbic System metabolism, Ovariectomy, Tissue Distribution, Estrogens pharmacology, Hypothalamus drug effects, Limbic System drug effects, Receptors, Progesterone biosynthesis
- 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
- Full Text
- View/download PDF
23. Estradiol and progesterone influence a serotonin mediated behavioral syndrome (myoclonus) in female guinea pigs: comparison with steroid effects on reproductive behavior.
- Author
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O'Connor LH and Feder HH
- Subjects
- 5-Hydroxytryptophan administration & dosage, Animals, Drug Interactions, Female, Guinea Pigs, Models, Neurological, Myoclonus physiopathology, Posture, Estradiol administration & dosage, Myoclonus chemically induced, Progesterone administration & dosage, Receptors, Progesterone physiology, Serotonin physiology, Sexual Behavior, Animal physiology
- 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
- Full Text
- View/download PDF
24. Long-term priming with a low dosage of estradiol benzoate or an antiestrogen (enclomiphene) increases nuclear progestin receptor levels in brain.
- Author
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Wilcox JN and Feder HH
- Subjects
- Animals, Brain drug effects, Castration, Cerebral Cortex metabolism, Clomiphene pharmacology, Cytosol metabolism, Female, Guinea Pigs, Isomerism, Kinetics, Organ Specificity, Progesterone metabolism, Promegestone metabolism, Receptors, Progesterone drug effects, Brain metabolism, Cell Nucleus metabolism, Clomiphene analogs & derivatives, Enclomiphene, Estradiol pharmacology, Receptors, Progesterone metabolism
- Published
- 1983
- Full Text
- View/download PDF
25. Intrahypothalamic implants of progesterone inhibit lordosis behavior in ovariectomized, estrogen-treated rats.
- Author
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Marrone BL, Rodriguez-Sierra JF, and Feder HH
- Subjects
- Animals, Castration, Drug Implants, Female, Rats, Estradiol pharmacology, Hypothalamus physiology, Posture, Progesterone pharmacology, Sexual Behavior, Animal drug effects
- Abstract
Intracranial implants of crystalline progesterone (P) were used to examine in site of action of P's facilitatory and inhibitory effects on lordosis behavior in the ovariectomized, estradiol-benzoate (EB)-primed RAT. P implanted in the medial basal hypothalamus (MBH) 1 h prior to subcutaneous (s.c.) EB injection inhibited lordosis in response to a systemic P injection 44 h after EB (concurrent inhibition). P implanted in the MBH did not facilitate lordosis when implanted 44 h after EB injection, but this same implant of P inhibited lordosis in response to P injection 68 h after EB (sequential inhibition). Cholesterol (Chol) implants in the MBH did not inhibit lordosis behavior in either the concurrent or the sequential inhibition experimental paradigms. The results indicate that the MBH is an important site of P inhibition of sexual receptivity in the rat.
- Published
- 1979
- Full Text
- View/download PDF
26. Stimulation of (3H)leucine incorporation into protein by estradiol-17beta or progesterone in brain tissues of ovariectomized guinea pigs.
- Author
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Wade GN and Feder HH
- Subjects
- Animals, Blood Proteins biosynthesis, Castration, Cerebral Cortex metabolism, Diaphragm metabolism, Drug Synergism, Female, Guinea Pigs, Hypothalamus metabolism, Leucine metabolism, Mesencephalon metabolism, Stimulation, Chemical, Tritium, Uterus metabolism, Brain metabolism, Estradiol pharmacology, Nerve Tissue Proteins biosynthesis, Progesterone pharmacology
- Published
- 1974
- Full Text
- View/download PDF
27. Urine-induced reflex ovulation in anovulatory rats may be a vomeronasal effect.
- Author
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Johns MA, Feder HH, Komisaruk BR, and Mayer AD
- Subjects
- Animals, Estrus radiation effects, Female, Light, Male, Pregnancy, Reflex physiology, Time Factors, Nasal Septum physiology, Olfactory Mucosa physiology, Ovulation, Rats physiology, Urine physiology
- Published
- 1978
- Full Text
- View/download PDF
28. Alpha 1-noradrenergic regulation of hypothalamic progestin receptors and guinea pig lordosis behavior.
- Author
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Nock B and Feder HH
- Subjects
- Animals, Brain Mapping, Clonidine pharmacology, Estradiol physiology, Female, Guinea Pigs, Phenoxybenzamine pharmacology, Posture, Prazosin pharmacology, Receptors, Progesterone drug effects, Hypothalamus physiology, Norepinephrine physiology, Receptors, Progesterone physiology, Sexual Behavior, Animal physiology
- 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
- Full Text
- View/download PDF
29. Reflex ovulation in light-induced persistent estrus (LLPE) rats: role of sensory stimuli and the adrenals.
- Author
-
Johns MA, Feder HH, and Komisaruk BR
- Subjects
- Animals, Female, Pregnancy, Rats, Sexual Behavior, Animal physiology, Adrenal Glands physiology, Estrus, Light, Ovulation, Reflex physiology, Sensation physiology
- Published
- 1980
- Full Text
- View/download PDF
30. Long term effects of estrogen action are crucial for the display of lordosis in female guinea pigs: antagonism by antiestrogens and correlations with in vitro cytoplasmic binding activity.
- Author
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Walker WA and Feder HH
- Subjects
- Animals, Castration, Cytosol metabolism, Estradiol metabolism, Estrogen Antagonists metabolism, Female, Guinea Pigs, Hypothalamus metabolism, Kinetics, Posture, Preoptic Area metabolism, Receptors, Estrogen metabolism, Estradiol pharmacology, Estrogen Antagonists pharmacology, Progesterone pharmacology, Sexual Behavior, Animal drug effects
- Published
- 1979
- Full Text
- View/download PDF
31. Multiple progesterone injections and the duration of estrus in ovariectomized guinea pigs.
- Author
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Morin LP and Feder HH
- Subjects
- Animals, Castration, Estradiol pharmacology, Female, Guinea Pigs, Injections, Subcutaneous, Oils, Pharmaceutical Vehicles, Pregnancy, Progesterone administration & dosage, Progesterone blood, Propylene Glycols, Radioimmunoassay, Sexual Behavior, Animal drug effects, Time Factors, Estrus drug effects, Progesterone pharmacology
- Published
- 1973
- Full Text
- View/download PDF
32. Testosterone and "5alpha-dihydrotestosterone" levels in peripheral plasma of male and female ring doves (Streptopelia risoria) during and reproductive cycle.
- Author
-
Feder HH, Storey A, Goodwin D, Reboulleau C, and Silver R
- Subjects
- Animals, Columbidae physiology, Courtship, Female, Male, Sexual Behavior, Animal, Testis physiology, Columbidae blood, Dihydrotestosterone blood, Reproduction, Testosterone blood
- Published
- 1977
- Full Text
- View/download PDF
33. Facilitation of lordosis in guinea pigs by an alpha-noradrenergic agonist is independent of progestin receptor stimulation.
- Author
-
Thornton JE, Vincent PA, and Feder HH
- Subjects
- Animals, Estradiol pharmacology, Estrenes pharmacology, Estrus drug effects, Female, Guinea Pigs, Male, Mifepristone, Ovariectomy, Progesterone pharmacology, Clonidine pharmacology, Receptors, Progesterone drug effects, Sexual Behavior, Animal drug effects
- Abstract
Because manipulations of the noradrenergic system affect both lordosis behavior and progestin receptor levels in female guinea pigs, the present study attempted to determine if the noradrenergic (NE) system affects lordosis solely because of its impact on progestin receptors. Although the progestin receptor antagonist RU486 significantly reduced progesterone-facilitated lordosis, it had no effect on lordosis induced by the alpha-NE agonist clonidine in estrogen-primed female guinea pigs. This indicates that although progesterone may facilitate lordosis in female guinea pigs via activation of progestin receptors, the alpha-noradrenergic agonist clonidine does not mediate lordosis through the same mechanism.
- Published
- 1988
- Full Text
- View/download PDF
34. Male and female sexual responses in male rats given estradiol benzoate and 5 alpha-androstan-17 beta-ol-3-one propionate.
- Author
-
Feder HH, Naftolin F, and Ryan KJ
- Subjects
- Animals, Castration, Dose-Response Relationship, Drug, Epididymis physiology, Estradiol administration & dosage, Female, Male, Posture, Rats, Testis physiology, Testosterone pharmacology, Dihydrotestosterone pharmacology, Estradiol pharmacology, Sexual Behavior, Animal drug effects
- Published
- 1974
- Full Text
- View/download PDF
35. Cytoplasmic progestin receptors in female guinea pig brain and their relationship to refractoriness in expression of female sexual behavior.
- Author
-
Blaustein JD and Feder HH
- Subjects
- Animals, Castration, Dose-Response Relationship, Drug, Estradiol pharmacology, Female, Guinea Pigs, Hypothalamus drug effects, Mesencephalon drug effects, Preoptic Area drug effects, Septum Pellucidum drug effects, Brain drug effects, Progesterone pharmacology, Receptors, Progesterone drug effects, Sexual Behavior, Animal drug effects
- Published
- 1979
- Full Text
- View/download PDF
36. Nuclear progestin receptors in guinea pig brain measured by an in vitro exchange assay after hormonal treatments that affect lordosis.
- Author
-
Blaustein JD and Feder HH
- Subjects
- Animals, Cell Nucleus drug effects, Estradiol pharmacology, Female, Guinea Pigs, Kinetics, Progesterone blood, Progesterone metabolism, Promegestone metabolism, Receptors, Progesterone drug effects, Brain metabolism, Cell Nucleus metabolism, Posture drug effects, Progesterone pharmacology, Receptors, Progesterone metabolism, Sexual Behavior, Animal drug effects
- Published
- 1980
- Full Text
- View/download PDF
37. Social interactions and androgen levels in birds. II. Social factors associated with a decline in plasma androgen levels in male ring doves (Streptopelia risoria).
- Author
-
O'Connell ME, Silver R, Feder HH, and Reboulleau C
- Subjects
- Animals, Courtship, Female, Male, Nesting Behavior physiology, Sex Factors, Androgens blood, Columbidae blood, Sexual Behavior, Animal physiology
- Published
- 1981
- Full Text
- View/download PDF
38. Distribution of cholinergic muscarinic binding sites in guinea-pig brain as determined by in vitro autoradiography of [3H]N-methyl scopolamine binding.
- Author
-
Dohanich GP, Johnson AE, Nock B, McEwen BS, and Feder HH
- Subjects
- Animals, Autoradiography, Basal Ganglia metabolism, Cerebral Cortex metabolism, Female, Geniculate Bodies, Guinea Pigs, In Vitro Techniques, Limbic System metabolism, Mesencephalon metabolism, N-Methylscopolamine, Neural Pathways metabolism, Radioligand Assay, Scopolamine Derivatives metabolism, Brain metabolism, Receptors, Muscarinic metabolism
- Abstract
The distribution of muscarinic binding sites was analyzed in regions of the guinea-pig brain with semi-quantitative densitometry of [3H]N-methyl scopolamine binding, a muscarinic antagonist. In the rostral forebrain, high levels of binding were detected in the caudate putamen, nucleus accumbens and olfactory tubercle while intermediate levels of binding were observed in the medial and lateral septum, bed nucleus, and vertical and horizontal limbs of the diagonal band. The hypothalamus displayed binding that ranged from low levels in the preoptic area to intermediate levels in the mammillary nucleus. In limbic areas such as the thalamus, amygdala and hippocampus, a heterogeneous pattern of binding was evident in various subregions which tended to correspond with known innervation by cholinergic afferents. In the midbrain, binding was high in the superficial layer of the superior colliculus and the medial geniculate while intermediate binding was recorded in the lateral geniculate and the lateral aspect of the central gray. The pattern of muscarinic binding observed in the brain of the guinea-pig is similar to distributions of this binding site previously reported in the rat brain and the human brain.
- Published
- 1985
- Full Text
- View/download PDF
39. Changes in noradrenergic transmission alter the concentration of cytoplasmic progestin receptors in hypothalamus.
- Author
-
Nock B, Blaustein JD, and Feder HH
- Subjects
- Animals, Cerebral Cortex drug effects, Clonidine pharmacology, Dopamine beta-Hydroxylase antagonists & inhibitors, Estradiol pharmacology, Female, Guinea Pigs, Phenoxybenzamine pharmacology, Preoptic Area drug effects, Progesterone pharmacology, Receptors, Adrenergic, alpha drug effects, Receptors, Progesterone drug effects, Sexual Behavior, Animal drug effects, Cytoplasm metabolism, Hypothalamus metabolism, Norepinephrine metabolism, Progestins metabolism, Receptors, Progesterone metabolism, Synaptic Transmission drug effects
- Published
- 1981
- Full Text
- View/download PDF
40. Characteristics of [3H]prazosin binding to guinea pig brain alpha-adrenergic receptors: effects of estradiol and progesterone.
- Author
-
Nock B and Feder HH
- Subjects
- Animals, Binding, Competitive, Cell Membrane metabolism, Female, Guinea Pigs, Kinetics, Receptors, Adrenergic, alpha drug effects, Structure-Activity Relationship, Brain metabolism, Estradiol pharmacology, Prazosin metabolism, Progesterone pharmacology, Quinazolines metabolism, Receptors, Adrenergic metabolism, Receptors, Adrenergic, alpha metabolism
- Abstract
[3H]Prazosin was found to bind to sites on guinea pig brain membranes with alpha 1-adrenergic receptor characteristics. Treatment of ovariectomized guinea pigs with estradiol benzoate (EB) or EB followed by progesterone (P) did not affect [3H]prazosin binding to membranes from hypothalamus, preoptic area, amygdala or cerebral cortex. When added to the incubation mixture of the assay, estradiol, P, and other steroids decreased [3H]prazosin binding but only at high concentrations. These results do not support the idea that estrogen and progestin influence reproductive physiology through effects on brain alpha 1-receptors, although limitations of the methodology employed do not completely rule out this possibility.
- Published
- 1983
- Full Text
- View/download PDF
41. Development of steroid-receptor systems in guinea pig brain. III. Nuclear progestin receptors.
- Author
-
Ryer HI and Feder HH
- Subjects
- Animals, Brain growth & development, Estradiol pharmacology, Female, Guinea Pigs, Male, Receptors, Progesterone drug effects, Time Factors, Animals, Newborn growth & development, Cell Nucleus metabolism, Cerebral Cortex metabolism, Hypothalamus metabolism, Receptors, Progesterone analysis, Receptors, Steroid physiology
- Abstract
Nuclear progestin receptors (NPR) were measured, with an exchange assay, in neonatal (4-6 days old) and adult (50-60 days old) guinea pigs of both sexes in order to further examine deficits in the neonatal hypothalamic progestin receptor system. Both neonatal and adult hypothalamus (HYPO) and cortex ( CORT ) contained a KCl extractable high affinity (Kd congruent to 0.1 nM) binder for R5020. In neonatal guinea pigs, given 10 micrograms estradiol benzoate (EB), NPR accumulation in HYPO and CORT peaked 2-4 h after a 0.5 mg injection of progesterone (P). There was no dose response of NPR to EB in neonatal HYPO, CORT or adult CORT . In adult HYPO, 10 micrograms EB-priming resulted in a higher concentration of NPR than 1.6 micrograms EB-priming. Neonatal HYPO (1.6 or 10 micrograms EB) did not differ in concentration of NPR from adult HYPO (1.6 micrograms EB). Neonatal CORT (1.6 or 10 micrograms EB) showed a lower NPR concentration than adult CORT (1.6 micrograms EB). There was a sex difference (females greater than males) in NPR concentration in both neonatal and adult HYPO, but not CORT . These results are discussed with regard to deficits in cytoplasmic progestin receptors and behavioral insensitivity to estrogen-progestin treatment found in neonatal guinea pigs.
- Published
- 1984
- Full Text
- View/download PDF
42. Estradiol modulation of alpha 2-noradrenergic receptors in guinea pig brain assessed by tritium-sensitive film autoradiography.
- Author
-
Johnson AE, Nock B, McEwen B, and Feder HH
- Subjects
- Animals, Autoradiography, Female, Guinea Pigs, Hypothalamus metabolism, Receptors, Adrenergic, alpha metabolism, Estradiol pharmacology, Hypothalamus drug effects, Receptors, Adrenergic, alpha drug effects
- Abstract
In this experiment, we examined the influence of estradiol on alpha 2-noradrenergic receptor binding in the female guinea pig brain with tritium-sensitive film autoradiography. Treatment of ovariectomized guinea pigs with estradiol increased alpha 2-receptor binding in regions of the preoptic area and decreased binding in the ventromedial nucleus of the hypothalamus. There was no effect of estradiol on alpha 2-receptor concentrations in other estradiol concentrating regions or in brain areas which do not concentrate estradiol.
- Published
- 1985
- Full Text
- View/download PDF
43. Role of the adrenal glands, repeated matings and monoamines in lordosis behavior of rats.
- Author
-
Larsson K, Feder HH, and Komisaruk BR
- Subjects
- Adrenalectomy, Animals, Body Weight, Castration, Estradiol pharmacology, Female, Male, Ovary physiology, Rats, Testis physiology, Time Factors, Adrenal Glands physiology, Posture drug effects, Progesterone pharmacology, Sexual Behavior, Animal drug effects, Tetrabenazine pharmacology
- Published
- 1974
- Full Text
- View/download PDF
44. Differential effects of prostaglandins on lordosis behavior in female guinea pigs and rats.
- Author
-
Marrone BL, Rodriguez-Sierra JF, and Feder HH
- Subjects
- Animals, Castration, Dose-Response Relationship, Drug, Estradiol pharmacology, Female, Guinea Pigs, Rats, Time Factors, Posture, Prostaglandins E pharmacology, Prostaglandins F pharmacology, Sexual Behavior, Animal
- Published
- 1979
- Full Text
- View/download PDF
45. Facilitation of lordosis behavior by clonidine in female guinea pigs.
- Author
-
Crowley WR, Nock BL, and Feder HH
- Subjects
- Animals, Castration, Estradiol pharmacology, Female, Guinea Pigs, Progesterone pharmacology, Stimulation, Chemical, Time Factors, Clonidine pharmacology, Sexual Behavior, Animal drug effects
- Abstract
Lordosis behavior was induced in previously unreceptive, ovariectomized estrogen-primed female guinea pigs by administration of the noradrenergic agonist clonidine. Clonidine also enhanced lordosis responding in females that were weakly receptive after estrogen priming. Unlike progesterone, the lordosis-facilitating effect of clonidine was not accompanied by a subsequent refractory period. Clonidine had a weak lordosis facilitatory effect when administered during the decline in receptivity to estrogen plus progesterone-primed animals and failed to induce lordosis when administered during the refractory period.
- Published
- 1978
- Full Text
- View/download PDF
46. Anti-estrogen effects on estrogen accumulation in brain cell nuclei: neurochemical correlates of estrogen action on female sexual behavior in guinea pigs.
- Author
-
Walker WA and Feder HH
- Subjects
- Animals, Brain drug effects, Brain ultrastructure, Castration, Cell Nucleus drug effects, Cerebral Cortex metabolism, Clomiphene pharmacology, Estradiol metabolism, Female, Hypothalamus metabolism, Mice, Nitromifene pharmacology, Pituitary Gland metabolism, Preoptic Area metabolism, Time Factors, Brain metabolism, Cell Nucleus metabolism, Estrogen Antagonists pharmacology, Estrogens metabolism, Sexual Behavior, Animal drug effects
- Published
- 1977
- Full Text
- View/download PDF
47. Serum progesterone concentrations and maternal behavior in rats after pregnancy termination: behavioral stimulation after progesterone withdrawal and inhibition by progesterone maintenance.
- Author
-
Bridges RS, Rosenblatt JS, and Feder HH
- Subjects
- Abortion, Induced, Animals, Behavior, Animal drug effects, Castration, Female, Hysterectomy, Pregnancy, Progesterone pharmacology, Rats, Maternal Behavior, Progesterone blood
- Published
- 1978
- Full Text
- View/download PDF
48. Uptake and metabolism of 3H-estrone in neural and peripheral tissue of gonadectomized adult and neonatal guinea pigs.
- Author
-
Landau IT and Feder HH
- Subjects
- Age Factors, Amygdala metabolism, Animals, Animals, Newborn metabolism, Cerebral Cortex metabolism, Female, Guinea Pigs, Hypothalamus metabolism, Male, Septum Pellucidum metabolism, Brain metabolism, Estrone metabolism, Seminal Vesicles metabolism, Uterus metabolism
- Published
- 1980
- Full Text
- View/download PDF
49. Cytosol androgen receptors in guinea pig brain and pituitary.
- Author
-
Bonneau M, Ahdieh HB, Thornton JE, and Feder HH
- Subjects
- Age Factors, Androgens metabolism, Animals, Brain metabolism, Cytosol analysis, Female, Guinea Pigs, Male, Pituitary Gland, Anterior metabolism, Prazosin pharmacology, Receptors, Androgen metabolism, Sex Characteristics, Brain Chemistry, Pituitary Gland, Anterior analysis, Receptors, Androgen analysis
- Abstract
Cytosol androgen receptors were assayed in guinea pig brain and pituitary tissues, using [3H]R1881 as ligand. These receptors had an apparent Kd of 0.04 nM and were androgen-specific (R1881 greater than dihydrotestosterone greater than testosterone = estradiol greater than progesterone). Concentrations of cytosol androgen receptors in castrated adult male guinea pigs were 12.2, 11.6, 6.9, 2.6 and 1.3 fmol per mg protein in anterior pituitary, hypothalamus, medial preoptic area, amygdala and cortex, respectively. No significant differences in receptor levels were observed between castrated adult males and females. The concentration of androgen receptors was significantly lower in the hypothalamus, medial preoptic area and anterior pituitary of castrated neonatal males than in castrated adult male guinea pigs. The systemic injection of the alpha 1-adrenergic antagonist, prazosin, had no significant influence on androgen receptor levels in castrated males in any brain area.
- Published
- 1987
- Full Text
- View/download PDF
50. Cytoplasmic progestin-receptors in guinea pig brain: characteristics and relationship to the induction of sexual behavior.
- Author
-
Blaustein JD and Feder HH
- Subjects
- 20-alpha-Dihydroprogesterone pharmacology, Animals, Brain physiology, Castration, Corticosterone pharmacology, Cytosol metabolism, Dose-Response Relationship, Drug, Estradiol pharmacology, Female, Guinea Pigs, Norgestrel pharmacology, Progesterone pharmacology, Promegestone pharmacology, Receptors, Progesterone drug effects, Sexual Behavior, Animal drug effects, Norpregnadienes metabolism, Promegestone metabolism, Receptors, Progesterone physiology, Sexual Behavior, Animal physiology
- Abstract
The synthetic progestin, R 5020, was used to measure cytoplasmic progestin receptors in the brain and pituitary gland of ovariectomized guinea pigs. Progestin receptors with a dissociation constant of 0.1--0.3 nM were measured by gel filtration in all brain regions studied, pituitary gland and the uterus. The receptor is progestin-specific; biologically potent progestins compete well against [3H]R 5020 for binding, but androgens, glucocorticoids and estrogens do not. The concentration of the cytoplasmic progestin receptor in hypothalamus-preoptic area-septum and midbrain is decreased in vivo by behaviorally effective doses of progesterone. In the pituitary gland, hypothalamus, preoptic area-septum and midbrain, but not other brain regions, the concentration of progestin receptors increases after estradiol benzoate-priming. The increase in the concentration of cytoplasmic progestin receptors in hypothalamus-preoptic area-septum is dependent on the dose of estradiol benzoate injected. After a single injection of a dose of estradiol benzoate routinely used to facilitate the display of sexual receptivity (1.6 microgram estradiol benzoate/animal), the latency to an increase and subsequent decrease in cytoplasmic progestin receptors in the hypothalamus-preoptic area-septum correlates well with the previously reported time course for progesterone's facilitation of sexual receptivity after estradiol benzoate injection. The experiments are consistent with the notion that brain progestin receptors mediate at least some of the behavioral effects of progesterone.
- Published
- 1979
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