214 results on '"Lipsett MB"'
Search Results
2. Effect of cortisol, T3 and T4, on the glucocorticoid receptor concentration in leukocytes.
- Author
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Murakami T, Brandon DD, Loriaux DL, and Lipsett MB
- Subjects
- Adrenocorticotropic Hormone metabolism, Animals, Dexamethasone metabolism, Female, Goats, Propylthiouracil metabolism, Hydrocortisone pharmacology, Leukocytes drug effects, Receptors, Glucocorticoid drug effects, Receptors, Steroid drug effects, Thyroxine pharmacology, Triiodothyronine pharmacology
- Published
- 1980
- Full Text
- View/download PDF
3. The mechanism of hypercortisolemia in the squirrel monkey.
- Author
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Cassorla FG, Albertson BD, Chrousos GP, Booth JD, Renquist D, Lipsett MB, and Loriaux DL
- Subjects
- Adrenal Glands anatomy & histology, Adrenal Glands enzymology, Adrenocorticotropic Hormone blood, Animals, Macaca fascicularis blood, Metabolic Clearance Rate, Microsomes enzymology, Organ Size, Receptors, Glucocorticoid metabolism, Species Specificity, Cebidae blood, Hydrocortisone blood, Saimiri blood
- Published
- 1982
- Full Text
- View/download PDF
4. Radioimmunoassay and metabolism of the catechol estrogen 2-hydroxyestradiol.
- Author
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Kono S, Merriam GR, Brandon DD, Loriaux DL, and Lipsett MB
- Subjects
- 2-Methoxyestradiol, Adult, Chromatography, Ion Exchange, Chromatography, Paper, Chromatography, Thin Layer, Estradiol blood, Female, Half-Life, Humans, Hydroxyestrones blood, Male, Metabolic Clearance Rate, Middle Aged, Radioimmunoassay, Estradiol analogs & derivatives
- Abstract
Plasma levels of 2-hydroxyestradiol (2-OHE2) were measured using a new RIA procedure. Values were below the detection limit of the assay (less than 10 pg/ml), except in the third trimester of pregnancy, when they rose to approximately 15 pg/ml. The infusion of 130 microgram/h purified 2-OHE2 elevated its plasma concentration to 155 pg/ml, consistent with a plasma MCR (MCRp) of approximately 20,000 liters/day. The infusion of [3H] 2-OHE2 to equilibrium and chromatographic separation of the extracted plasma metabolites yielded an MCRp of about 13,000 liters/day; the major plasma metabolite comigrated with 2-methoxyestradiol, and [3H] xi-methoxyestrone was also formed. The MCRp, of 2-OHE2 is approximately half that of 2-hydroxyestrone (2-OHE1), but much higher than those of other steroids. As is true for 2-OHE1, the clearance of 2-OHE2 must occur primarily in the blood compartment. Together, the measured MCRp values and estrogen receptor affinities of 2-OHE2 and 2-OHE1 predict a relative potency for effects upon gonadotropin secretion which is close to that observed in vivo.
- Published
- 1982
- Full Text
- View/download PDF
5. Interaction of drugs, hormones, and nutrition in the causes of cancer.
- Author
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Lipsett MB
- Subjects
- Anovulation complications, Breast Neoplasms etiology, Estradiol Congeners adverse effects, Estriol metabolism, Estrogens physiology, Female, Hormones physiology, Humans, Liver Neoplasms etiology, Male, Ovarian Neoplasms etiology, Pregnancy, Progesterone Congeners pharmacology, Prolactin physiology, Prostatic Neoplasms etiology, Testosterone Congeners adverse effects, Uterine Neoplasms etiology, Vaginal Neoplasms etiology, Hormones pharmacology, Neoplasms etiology, Nutritional Physiological Phenomena
- Abstract
Hormones may act as promoters in the carcinogenic process, and occasionally their metabolites may act as antihormones or have new physiologic effects. Drugs can interact with the endocrine system in many ways. They can promote secretion of a hormone, alter its rate of removal from plasma, change plasma protein-binding characteristics, or modify routes of metabolism. Estrogens have a preparative effect on the uterine endometrium. There are biologic, clinical and epidemiologic reasons for believing that estrogen administration to postmenopausal women increases the risk for endometrial cancer. Although there are similar biologic reasons to associate prolonged estrogenic stimulation with breast cancerr, evidence for such an association is weak. Oral contraceptive use has been associated with a variety of hepatocellular tumors. Although estrogens, per se, can effect several hepatic functions, it seems likely that the 17 alpha-alkyl and 17 alpha-ethinyl functions of the progestins and estrogens are involved in this process. The role of estrogen use during pregnancy in the causation of vaginal cancer in female offspring and the role of androgens in prostate cancer have been discussed.
- Published
- 1979
- Full Text
- View/download PDF
6. Hypothalamic dysfunction in patients with anorexia nervosa.
- Author
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Mecklenburg RS, Loriaux DL, Thompson RH, Andersen AE, and Lipsett MB
- Subjects
- Adult, Animals, Anorexia Nervosa blood, Anorexia Nervosa diagnosis, Anorexia Nervosa diagnostic imaging, Anorexia Nervosa etiology, Body Temperature Regulation, Body Weight, Carbohydrate Metabolism, Diabetes Insipidus diagnosis, Electroencephalography, Estradiol blood, Female, Follicle Stimulating Hormone blood, Gonadotropin-Releasing Hormone pharmacology, Gonadotropins urine, Growth Hormone metabolism, Humans, Luteinizing Hormone blood, Mice, Pituitary-Adrenal System, Prolactin blood, Radiography, Sella Turcica diagnostic imaging, Thyroid Function Tests, Visual Field Tests, Anorexia Nervosa physiopathology, Hypothalamus physiopathology
- Published
- 1974
- Full Text
- View/download PDF
7. Postoperative radiation for women with cancer of the breast and positive axillary lymph nodes: should it continue?
- Author
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Lipsett MB
- Subjects
- Axilla, Breast Neoplasms mortality, Breast Neoplasms surgery, Female, Humans, Lymphatic Metastasis, Mastectomy, Neoplasm Staging, Postoperative Care, Breast Neoplasms radiotherapy
- Published
- 1981
- Full Text
- View/download PDF
8. Hormonal correlates of normal and abnormal follicle growth after puberty in humans and other primates.
- Author
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Ross GT and Lipsett MB
- Subjects
- Animals, Contraceptives, Oral pharmacology, Corpus Luteum physiology, Female, Follicle Stimulating Hormone blood, Follicular Phase, Humans, Hypogonadism physiopathology, Luteal Phase, Luteinizing Hormone blood, Menstruation, Ovarian Follicle drug effects, Ovulation, Ovulation Induction, Pregnancy, Prolactin physiology, Puberty, Time Factors, Ovarian Follicle growth & development
- Abstract
After the menarche, changing levels of gonadotrophins, prolactin and sex steroid hormones in peripheral blood are accompanied by ovulation and corpus luteum formation in one follicle, and atresia in the remaining follicles maturing during each menstrual cycle. Available evidence suggests that blood levels of steroid hormones reflect in large part the secretory activity of the ovary containing a pre-ovulatory follicle and most probably of that follicle itself (see Chapter 6). These steroid secretions and those of the corpus luteum coordinate hypothalamic-pituitary-ovarian function. Within the ovary, sex steroid hormones mediate effects of gonadotrophins and prolactin on follicle maturation and participate in determining the fate of individual follicles.
- Published
- 1978
- Full Text
- View/download PDF
9. Physiology and pathology of the Leydig cell.
- Author
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Lipsett MB
- Subjects
- Adult, Aging, Animals, Child, Chorionic Gonadotropin physiology, Cryptorchidism physiopathology, Ethanol adverse effects, Eunuchism physiopathology, Gonadotropins, Pituitary physiology, Humans, Hypogonadism physiopathology, Hypopituitarism physiopathology, Klinefelter Syndrome physiopathology, Leydig Cells drug effects, Leydig Cells metabolism, Male, Noonan Syndrome physiopathology, Nutrition Disorders physiopathology, Rabbits, Rats, Sex Chromosome Aberrations physiopathology, Syndrome, Testicular Diseases physiopathology, Testis metabolism, Testis physiology, Disorders of Sex Development physiopathology, Leydig Cells physiology, Testis physiopathology
- Published
- 1980
- Full Text
- View/download PDF
10. Effect of receptor occupancy on [3H]dexamethasone binding to circulating leukocytes.
- Author
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Murakami T, Brandon DD, Loriaux DL, and Lipsett MB
- Subjects
- Animals, Female, Glucocorticoids pharmacology, Goats, Hydrocortisone pharmacology, Indicators and Reagents, Methods, Dexamethasone blood, Leukocytes metabolism, Receptors, Glucocorticoid analysis, Receptors, Steroid analysis
- Abstract
To determine the effect of steroid occupancy of the glucocorticoid receptor on the measurement of total receptor concentration using Scatchard plot of [3H]dexamethasone (Dex) binding to circulating leukocytes, leukocytes were incubated with 10(-7)M cortisol or 10(-9)M Dex prior to [3H]Dex binding study. Total binding capacity calculated from Scatchard plot analysis of [3H]Dex binding was not significantly reduced after pre-incubation with cortisol. However, total binding capacity was significantly lower after pre-incubation with Dex. These data suggest that total glucocorticoid receptor concentration can be measured from a 3 h incubation of leukocytes obtained from untreated patients.
- Published
- 1980
- Full Text
- View/download PDF
11. On the nature and ethics of phase I clinical trials of cancer chemotherapies.
- Author
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Lipsett MB
- Subjects
- Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Ethics Committees, Research, Humans, Informed Consent, National Institutes of Health (U.S.), Personal Autonomy, Persons, Risk, Risk Assessment, United States, Vulnerable Populations, Antineoplastic Agents therapeutic use, Drug Evaluation, Ethics, Medical, Neoplasms drug therapy
- Published
- 1982
12. Catechol estrogens and the control of gonadotropin and prolactin secretion in man.
- Author
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Merriam GR, Pfeiffer DG, Loriaux DL, and Lipsett MB
- Subjects
- Animals, Dose-Response Relationship, Drug, Female, Follicular Phase, Humans, Kinetics, Male, Rats, Reference Values, Estradiol analogs & derivatives, Estrogens, Catechol, Estrone analogs & derivatives, Follicle Stimulating Hormone metabolism, Hydroxyestrones, Luteinizing Hormone metabolism, Prolactin metabolism
- Abstract
The catechol estrogens, the 2- or 4-hydroxylated metabolites of estrone and estradiol, have pharmacologic properties of both estrogens and catecholamines and are formed from estrogens in peripheral tissues and in the brain. This has led to speculation that they may mediate some of the feedback effects of estrogens upon gonadotropins and prolactin (PRL). Studies testing these hypotheses are still few and have not been conclusive. There have been reports that the catechol estrogen 2-hydroxyestrone (2-OHE1) might act as a partial estrogen antagonist, stimulating gonadotropin secretion; and that it might have dopamine-like effects, suppressing the secretion of PRL. In studies testing the chronic and acute effects of catechol estrogens on LH, FSH, and PRL in men and women, we found that they behaved as estrogens, suppressing gonadotropins when given in doses high enough to compensate for their rapid clearance and degradation. We found no evidence that they suppress PRL secretion. The weight of available evidence suggests that these effects are mediated by estrogen receptor interactions; and that the formation of catechol estrogens is not an obligatory step in the feedback effects of estrogens, although it may have a modulatory role. Plasma levels of catechol estrogens are too low for them to exert circulating neuroendocrine effects.
- Published
- 1983
- Full Text
- View/download PDF
13. Severe osteopenia in young adults associated with Cushing's syndrome due to micronodular adrenal disease.
- Author
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Ruder HJ, Loriaux DL, and Lipsett MB
- Subjects
- 17-Hydroxycorticosteroids urine, 17-Ketosteroids urine, Adrenal Glands pathology, Adrenocorticotropic Hormone blood, Adult, Age Determination by Skeleton, Angiography, Back Pain, Cortisone therapeutic use, Cushing Syndrome diagnosis, Dexamethasone, Female, Fludrocortisone therapeutic use, Humans, Hydrocortisone urine, Male, Radioimmunoassay, Rib Fractures etiology, Adrenal Gland Diseases complications, Bone Diseases etiology, Cushing Syndrome complications
- Published
- 1974
- Full Text
- View/download PDF
14. Radioimmunoassay and metabolic clearance rate of catecholestrogens, 2-hydroxyestrone and 2-hydroxyestradiol in man.
- Author
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Kono S, Merriam GR, Brandon DD, Loriaux DL, Lipsett MB, and Fujino T
- Subjects
- Adult, Blood Pressure, Child, Child, Preschool, Estradiol blood, Estrogens blood, Female, Humans, Kinetics, Male, Menstruation, Metabolic Clearance Rate, Pre-Eclampsia blood, Pregnancy, Radioimmunoassay methods, Estradiol analogs & derivatives, Estrogens, Catechol blood, Estrone analogs & derivatives, Hydroxyestrones blood
- Abstract
Plasma levels of 2-hydroxyestrone (2-OHE1) and 2-hydroxyestradiol (2-OHE2) were determined by a new radioimmunoassay which employed a short Sephadex LH-20 column chromatography for the purification of samples and the antiserum to 2-hydroxyestrone-17-(O-carboxymethyl)oxime-BSA conjugate for assay. The plasma value was below the detection limit for the assay (approximately 15 pg/ml) in men and non-pregnant women, but rose 20-200 pg/ml during pregnancy in 2-OHE1 and around 15 pg/ml in the 3rd trimester of pregnancy in 2-OHE2. There was no significant difference of plasma 2-OHE1 level between normal pregnancy and toxemic pregnancy with hypertension, in the 3rd trimester. The plasma level was very low in all of three subjects with the placental dysfunction in toxemic pregnancy. The plasma metabolic clearance rate (MRCp) of 2-OHE1 and 2-OHE2 were determined in normal adults by two methods; infusion of unlabeled 2-OHE1 and 2-OHE2 to equilibrium with radioimmunoassay of their plasma levels, and infusion of [3H]-2-OHE1 and [3H]-2-OHE2 to equilibrium with measurement of chromatographically purified their tritium. The MCRs by the former and latter methods was 40-70 X 10(3) and 15-50 X 10(3) in 2-OHE1, and 18-29 X 10(3) and 12-14 X 10(3) l/day in 2-OHE2, respectively. The major plasma metabolite comigrated with 2-methoxy compounds to each catecholestrogen. The t1/2 of disappearance rate by the method of infusion of unlabeled compounds was approx. 45 s in 2-OHE1 and 90 s in 2-OHE2. When [3H]-2-OHE1 and [3H]-2-OHE2 were incubated with blood samples of adults, 2-methoxy compounds also rapidly formed. From these results it is concluded that the extremely high MCRp of 2-OHE1 and 2-OHE2 make it unlikely these compounds circulate peripherally except in pregnancy in levels sufficient to produce the physiological effects on estrogen receptors or catecholamines.
- Published
- 1983
- Full Text
- View/download PDF
15. Glucocorticoid hormone resistance during primate evolution: receptor-mediated mechanisms.
- Author
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Chrousos GP, Renquist D, Brandon D, Eil C, Pugeat M, Vigersky R, Cutler GB Jr, Loriaux DL, and Lipsett MB
- Subjects
- Animals, Dexamethasone pharmacology, Humans, Hydrocortisone urine, Leukocytes metabolism, Protein Binding, Species Specificity, Biological Evolution, Hydrocortisone blood, Primates physiology, Receptors, Glucocorticoid drug effects, Receptors, Steroid drug effects
- Abstract
The concentrations of total and protein-unbound plasma cortisol of New World monkeys are higher than those of Old World primates and prosimians. The urinary free-cortisol excretion also is increased markedly. However, there is no physiologic evidence of increased cortisol effect. These findings suggest end-organ resistance to glucocorticoids. This was confirmed by showing that the hypothalamic-pituitary adrenal axis is resistant to suppression by dexamethasone. To study this phenomenon, glucocorticoid receptors were examined in circulating mononuclear leukocytes and cultured skin fibroblasts from both New and Old World species. The receptor content is the same in all species, but the New World monkeys have a markedly decreased binding affinity for dexamethasone. Thus, the resistance of these species to the action of cortisol is due to the decreased binding affinity of the glucocorticoid receptor. This presumed mutation must have occurred after the bifurcation of Old and New World primates (approximately 60 x 10(6) yr ago) and before the diversion of the New World primates from each other (approximately 15 x 10(6) yr ago).
- Published
- 1982
- Full Text
- View/download PDF
16. Plasma cortisol transport and primate evolution.
- Author
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Pugeat MM, Chrousos GP, Nisula BC, Loriaux DL, Brandon D, and Lipsett MB
- Subjects
- Animals, Callitrichinae blood, Cebidae blood, Chromatography, Gel, Concanavalin A, Electrophoresis, Polyacrylamide Gel, Macaca blood, Pan troglodytes blood, Papio blood, Sepharose, Strepsirhini blood, Biological Evolution, Hydrocortisone blood, Primates blood, Transcortin metabolism
- Abstract
Primates have diverged into three major evolutionary groups: prosimians, Old World primates, and New World primates; the last group is distinguished by high circulating cortisol concentrations and resistance to the action of glucocorticoids. We have studied a large spectrum of primate species within these groups to characterize the phylogenetic relationships of cortisol-binding globulin (CBG) among them. The CBG in each species was found to be glycosylated, as judged from lectin interactions, and to exhibit an electrophoretic mobility similar to that of human CBG. Although the CBG affinity for cortisol differed among species, the effects of changes in temperature on the CBG affinity were similar. Strikingly, the CBG-binding capacity of plasma in the New World primates was 1/10th to 1/100th those in the Old World primates and prosimians, while the CBG-binding affinity for cortisol was lower. The reduced capacity and affinity of CBG result in a markedly higher fraction of unbound plasma cortisol in the New World primates than in the Old World primates or the prosimian species examined. This evolutionary pattern of CBG may be a compensatory mechanism for the target organ resistance to glucocorticoids that characterizes the New World monkeys.
- Published
- 1984
- Full Text
- View/download PDF
17. Metabolic clearance rate and uterotropic activity of 2-hydroxyestrone in rats.
- Author
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Kono S, Brandon DD, Merriam GR, Loriaux DL, and Lipsett MB
- Subjects
- Animals, Cytosol metabolism, Female, Hydroxyestrones metabolism, Hydroxyestrones pharmacology, Metabolic Clearance Rate, Rats, Uterus metabolism, Estrone analogs & derivatives, Hydroxyestrones physiology, Uterine Contraction drug effects
- Abstract
2-Hydroxyestrone (2-OHE1) has much lower uterotropic potency than might be predicted from its uterine estrogen receptor affinity. 2-OHE1 displaces saturably bound [3H]estradiol from rat uterine cytosol with a competitive inhibition constant of 8.6 nM, while the dissociation constant for 17 beta-estradiol (E2) is 0.42 nM. From this ratio of binding affinities, one would expect some agonist or antagonist activity of 2-OHE1 to be apparent at doses roughly 20-50 times the minimum effective dose of E2. Instead, at doses of 2-OHE1 1000 times an effective dose of E2, no uterotropic effect was observed. When 2-OHE1 was injected together with E2 at dose ratios of 500:1, there was no antagonism of the effect of E2. To examine this discrepancy, the plasma MCRs (MCRpS) of E2 and 2-OHE1 were determined by continuous infusion techniques. Plasma concentrations of 2-OHE1 and E2 during control and infusion periods were measured by RIAs. The MCRp of 2-OHE1 averaged 50,000 ml/h, more than 100 times that of E2 (approximately 400 ml/h). The extraordinarily high MCRp of 2-OHE1 may explain the failure to observe any biological effects of this catechol estrogen, even at high doses. This rapid metabolism, presumably occurring in the blood compartment, should be considered in handling blood samples for RIA and in devising studies of the actions of catechol estrogens.
- Published
- 1981
- Full Text
- View/download PDF
18. Achievements in preventing morbidity and mortality by researchers of the National Institute of Child Health and Human Development.
- Author
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Lipsett MB
- Subjects
- Accident Prevention, Congenital Abnormalities prevention & control, Ethnicity, Family Planning Services, Humans, Hypertension prevention & control, Immunization, Infant, Newborn, Intellectual Disability, Lead Poisoning prevention & control, Nonprescription Drugs, Physical Fitness, United States, Child Health Services trends, Infant Mortality, Morbidity, National Institutes of Health (U.S.), Research Support as Topic
- Abstract
In the 20 years since its creation, the National Institute of Child Health and Human Development (NICHD) has become a world leader in promoting research on fertility, high-risk pregnancy, care of newborns, nutrition, learning disorders, mental retardation, development of better contraceptives, and factors that influence family planning. NICHD also supports basic research that sheds light on normal processes in human development.This research has yielded impressive dividends. Improvement in the treatment of premature infants has contributed to a 22 percent decline in infant mortality in the United States between 1976 and 1980. Between 1962 and 1980, the maternal death rate from pregnancy and childbirth dropped 80 percent, owing largely to NICHD-supported research that has led to improved management of a number of conditions that are life-threatening to pregnant women.NICHD-supported research has led to the development of screening tests and treatments for certain metabolic disorders that cause mental retardation. Grantees of the Institute have also discovered a chromosomal disorder known to be a cause of mental retardation in men and have made research advances leading to better home care and a fuller role in community life for persons with Down's syndrome.Other NICHD studies seek to improve family planning methods and to find safer, more effective contraceptives. A promising development in this area is a class of synthetic brain hormones that could provide a new type of birth control pill for women and the first successful chemical contraceptive for men.
- Published
- 1983
19. The social significance of endocrinology. Presidential address. 62nd Annual Meeting of The Endocrine Society.
- Author
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Lipsett MB
- Subjects
- Endocrinology methods, Female, Hormones therapeutic use, Humans, Male, Preventive Medicine, Reproduction, Societies, Scientific, Endocrinology trends
- Published
- 1980
- Full Text
- View/download PDF
20. Glucocorticoid receptors in Epstein-Barr virus-transformed lymphocytes from patients with glucocorticoid resistance and a glucocorticoid-resistant New World primate species.
- Author
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Tomita M, Brandon DD, Chrousos GP, Vingerhoeds AC, Foster CM, Fowler D, Loriaux DL, and Lipsett MB
- Subjects
- Animals, Callitrichinae, Cell Nucleus metabolism, Chromatography methods, Cytosol metabolism, Drug Resistance, Electrophoresis, Polyacrylamide Gel, Herpesvirus 4, Human, Hot Temperature, Humans, Male, B-Lymphocytes metabolism, Cell Transformation, Viral, Glucocorticoids pharmacology, Receptors, Glucocorticoid metabolism
- Abstract
Members of a previously reported family with glucocorticoid resistance and several New World primates have high plasma cortisol concentrations without any signs of glucocorticoid excess. The glucocorticoid receptor in circulating leukocytes and cultured skin fibroblasts from these patients and the animals is characterized by a decreased affinity for dexamethasone. On the other hand, the cell content of receptor is similar to that of corresponding tissues of normal humans. Detailed biochemical-biophysical studies of the glucocorticoid receptor in this familial syndrome and animal model became possible with the use of Epstein-Barr virus-transformed lymphocyte lines. Cell lines from patients with this syndrome and from the marmoset (Saguinus oedipus) contained decreased amounts of glucocorticoid receptors with concomitant decreases in nuclear receptor content compared to cultured Epstein-Barr virus-transformed lymphocytes from normal human subjects. This may reflect diminished induction of glucocorticoid receptor during viral transformation of cells from the patients and the animal model. Receptors from a severely affected glucocorticoid-resistant patient and the marmoset had decreased affinity for dexamethasone. Evidence for a mild affinity defect of the glucocorticoid receptor in a patient with asymptomatic glucocorticoid resistance was obtained by increased hormone-receptor dissociation at an elevated temperature. Thermal stability, mero-receptor formation, thermal activation of cytosolic receptor, and mol wt of receptors from all cell lines were normal. Only the receptors of the severely affected patient had a discernible defect in temperature-induced activation of intact cells. We conclude that the major detectable change in the receptor in both the patients and the animal model is the decreased affinity for glucocorticoid. Viral receptor induction is decreased in both patient and marmoset cells. The physiological relevance of this phenomenon is not known. Gross receptor molecule changes or changes in its stability at higher temperatures were not found. Mixing studies did not show involvement of cytosolic modifiers or inhibitors. Mutation(s) of the receptor molecule leading to low affinity for the hormone is the most likely explanation of the isolated glucocorticoid resistance in the patients. The glucocorticoid resistance of the New World primate, which is part of generalized steroid hormone resistance, appears to be a result of more complex changes.
- Published
- 1986
- Full Text
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21. Plasma steroids in congenital adrenal hyperplasia.
- Author
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Loriaux DL, Ruder HJ, and Lipsett MB
- Subjects
- 17-alpha-Hydroxypregnenolone blood, Adrenal Hyperplasia, Congenital, Adrenocortical Hyperfunction genetics, Androstenediols blood, Dehydroepiandrosterone blood, Humans, Hydrocortisone blood, Hydroxyprogesterones blood, Progesterone blood, Adrenocortical Hyperfunction blood, Steroids blood
- Published
- 1974
- Full Text
- View/download PDF
22. Special report. Steroid receptors in breast cancer.
- Author
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DeSombre ER, Carbone PP, Jensen EV, McGuire WL, Wells SA Jr, Wittliff JL, and Lipsett MB
- Subjects
- Animals, Breast Neoplasms drug therapy, Breast Neoplasms secondary, Breast Neoplasms therapy, Cytosol analysis, Female, Humans, Methods, Prognosis, Breast Neoplasms analysis, Receptors, Estrogen analysis
- Published
- 1979
- Full Text
- View/download PDF
23. Glucocorticoid receptor in circulating mononuclear leukocytes.
- Author
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Murakami T, Brandon D, Rodbard D, Loriaux DL, and Lipsett MB
- Subjects
- Animals, Binding, Competitive, Cell Nucleus metabolism, Cytosol metabolism, Female, Goats, Kinetics, Structure-Activity Relationship, Dexamethasone blood, Hydrocortisone blood, Neutrophils metabolism, Receptors, Glucocorticoid metabolism, Receptors, Steroid metabolism
- Published
- 1979
- Full Text
- View/download PDF
24. Primary cortisol resistance: a familial syndrome and an animal model.
- Author
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Chrousos GP, Loriaux DL, Brandon D, Tomita M, Vingerhoeds AC, Merriam GR, Johnson EO, and Lipsett MB
- Subjects
- Adrenal Gland Diseases metabolism, Adult, Animals, Biological Evolution, Dexamethasone, Disease Models, Animal, Drug Resistance, Female, Humans, Hydrocortisone blood, Male, Middle Aged, Pedigree, Primates, Receptors, Glucocorticoid metabolism, Reference Values, Skin metabolism, Steroids blood, Adrenal Gland Diseases genetics, Hydrocortisone metabolism, Hypothalamo-Hypophyseal System metabolism, Pituitary-Adrenal System metabolism
- Abstract
Primary cortisol resistance in man is a familial disease. It is characterized by increased plasma cortisol concentrations, high urinary free cortisol excretion, a normal circadian pattern of cortisol secretion, resistance to adrenal suppression by dexamethasone and absence of clinical stigmata of Cushing's syndrome. In its severe form, hypertension and hypokalemic alkalosis are present, owing to increased secretion of the sodium-retaining corticoids, corticosterone and deoxycorticosterone. In subjects with a less severe resistance to cortisol, there are no clinical abnormalities and the disease is revealed only by detailed examination of several parameters of cortisol metabolism. In the whole-cell assay (peripheral mononuclear leukocytes or fibroblasts) the glucocorticoid receptor shows a low affinity for dexamethasone. The receptor may be unsaturable as suggested by decreased receptor concentrations in broken-cell systems. Thus, generalized target-tissue resistance to cortisol, including the pituitary gland and the hypothalamus, is accompanied by a decreased negative feedback of the cortisol-ACTH feedback system resulting in increased ACTH secretion. This causes higher plasma cortisol to compensate for the end-organ resistance and also increases the production of adrenal mineralocorticoids, as by-products. Thus hypertension and hypokalemic alkalosis depends on the degree of the resistance. Cortisol resistance in many New World primate species is characterized by greatly increased plasma cortisol concentrations, decreased cortisol binding globulin capacity and affinity, high levels of plasma and urinary free cortisol, marked resistance of ACTH suppression by dexamethasone, and no physiologic evidence of glucocorticoid hormone excess. Target tissues have normal concentrations of glucocorticoid receptors with decreased affinity for dexamethasone. The New World primates, unlike man, have compensated for this cortisol resistance with intra-adrenal adaptations over the 50 million years of their evolutionary development. These primates also have abnormalities of other steroid hormone-receptor systems such as progesterone, estrogen, androgen and mineralocorticoid. In contrast, the human syndrome appears to be a recent mutation with pathophysiologic consequences.
- Published
- 1983
- Full Text
- View/download PDF
25. The squirrel monkey: receptor-mediated end-organ resistance to progesterone?
- Author
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Chrousos GP, Renquist D, Brandon D, Barnard D, Fowler D, Loriaux DL, and Lipsett MB
- Subjects
- Animals, Cercopithecidae, Female, Progesterone blood, Promegestone metabolism, Saimiri, Uterus analysis, Menstruation, Progesterone metabolism, Receptors, Progesterone metabolism
- Abstract
Fertile females of a New World primate species, the squirrel monkey (Saimiri sciureus), have plasma progesterone concentrations that vary between 57 and 510 ng/ml during the reproductive cycle and are 10- to 20-fold higher than those seen in cynomolgus monkeys (Macaca fascicularis) and other Old World primates, including man. The plasma progesterone level during pregnancy is high and varies between 140 and 490 ng/ml. Estradiol levels during the reproductive cycle and pregnancy are also higher than those of cynomolgus monkeys. After 2-day treatment of ovariectomized monkeys with estradiol in oil, the progesterone receptor content in the uterine cytosol of the squirrel monkey is one eighth that in similarly treated cynomolgus monkeys [60.4 +/- 6.5 fmol R5020 bound/mg protein vs. 496 +/- 55 (mean +/- SE); n = 8]. The receptor affinity for R5020 is the same in both species. Thus, the elevated plasma progesterone levels in squirrel monkeys appear to be a compensatory response to a receptor-mediated decrease in sensitivity to progesterone. The squirrel monkey may be a model for the study of the mechanism of action and regulation of secretion of progesterone.
- Published
- 1982
- Full Text
- View/download PDF
26. Ethics of Laetrile clinical trials.
- Author
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Lipsett MB and Fletcher JC
- Subjects
- Humans, Amygdalin therapeutic use, Drug Evaluation, Ethics, Medical, Neoplasms drug therapy, Nitriles therapeutic use
- Published
- 1977
- Full Text
- View/download PDF
27. Primary cortisol resistance: a family study.
- Author
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Chrousos GP, Vingerhoeds AC, Loriaux DL, and Lipsett MB
- Subjects
- Adrenocortical Hyperfunction blood, Adrenocortical Hyperfunction drug therapy, Dexamethasone therapeutic use, Drug Resistance, Female, Humans, Hydrocortisone blood, Male, Pedigree, Adrenocortical Hyperfunction genetics, Hydrocortisone urine
- Abstract
Primary cortisol resistance is an autosomal disease characterized by increased plasma cortisol concentration and high urinary free cortisol, resistance to adrenal suppression by dexamethasone, and the absence of clinical stigmata of Cushing's syndrome. The proband with the severe form had hypertension and hypokalemic alkalosis. In subjects with a less severe resistance to cortisol, there are no clinical abnormalities and the condition is revealed only by detailed examination of several parameters of cortisol secretion.
- Published
- 1983
- Full Text
- View/download PDF
28. The effects of temperature on the activity of testicular steroidogenic enzymes.
- Author
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Munabi AK, Cassorla FG, D'Agata R, Albertson BD, Loriaux DL, and Lipsett MB
- Subjects
- Aldehyde-Lyases metabolism, Animals, Aromatase metabolism, Cortisone Reductase metabolism, Horses, Leydig Cells enzymology, Male, Microsomes enzymology, Rats, Rats, Inbred Strains, Steroid 17-alpha-Hydroxylase metabolism, Swine, Temperature, Testis enzymology
- Abstract
Decreased sperm counts and impaired sperm motility are present in a substantial proportion of men with varicocele. Elevations in the temperature of the affected testis, and increased spermatic vein estradiol (E2) concentrations have been found in some of these patients. To investigate the possibility that increases in temperature lead to a pattern of testicular steroidogenesis that results in increased E2 synthesis, we have examined the effects of temperature changes on the activities of four important testicular steroidogenic enzymes. 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), 17-hydroxylase (17-OH), 17,20-desmolase (17,20-D) and aromatase activities were measured in the microsomal fraction of rat, pig and horse testes. Incubations were performed at 34 degrees C, 36 degrees C, and 38 degrees C. The activities of all 4 enzymes increased with each 2 degrees C temperature elevation in roughly proportional amounts. We conclude that minor elevations in incubation temperature are associated with increases in the in vitro activity of four key testicular steroidogenic enzymes.
- Published
- 1984
- Full Text
- View/download PDF
29. Plasma testosterone transport in primates.
- Author
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Pugeat M, Rocle B, Chrousos GP, Dunn JF, Lipsett MB, and Nisula BC
- Subjects
- Animals, Biological Transport, Active, Chromatography, Affinity, Chromatography, Gel, Electrophoresis, Polyacrylamide Gel, Sex Hormone-Binding Globulin metabolism, Species Specificity, Primates blood, Testosterone blood
- Abstract
All primate species, including Old and New World primates and prosimians have a plasma testosterone-estradiol binding globulin (TeBG), which is a glycoprotein and has a similar mobility in polyacrylamide gel electrophoresis. In New World primates the TeBG binding capacity for [3H]testosterone was higher and its affinity lower than in Old World primates. These changes were associated with high unbound plasma testosterone concentrations in these species. Binding parameters of TeBG in prosimian species varied markedly. Thus, in primate evolution TeBG was conserved despite marked differences in binding characteristics. In New World primates changes are associated with high total and unbound testosterone, a finding concordant with alterations of other steroid hormones concentration in these species with "generalized steroid hormone resistance".
- Published
- 1984
- Full Text
- View/download PDF
30. Mechanisms of corticosteroid action on lymphocyte subpopulations. VI. Lack of correlation between glucocorticosteroid receptors and the differential effects of glucocorticosteroids on T-cell subpopulations.
- Author
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Fauci AS, Murakami T, Brandon DD, Loriaux DL, and Lipsett MB
- Subjects
- Concanavalin A pharmacology, Dexamethasone pharmacology, Humans, Lymphocyte Activation drug effects, T-Lymphocytes classification, Thymidine metabolism, Adrenal Cortex Hormones pharmacology, Glucocorticoids pharmacology, Lymphocytes classification, Receptors, Glucocorticoid drug effects, Receptors, Steroid drug effects, T-Lymphocytes drug effects
- Published
- 1980
- Full Text
- View/download PDF
31. The role of testosterone and other hormones in regulation of LH.
- Author
-
Lipsett MB
- Subjects
- Animals, Dihydrotestosterone pharmacology, Feedback, Female, Follicle Stimulating Hormone metabolism, Growth Hormone, Humans, Male, Prolactin blood, Rats, Testosterone blood, Testosterone pharmacology, Androgens pharmacology, Estrogens pharmacology, Luteinizing Hormone metabolism
- Published
- 1979
- Full Text
- View/download PDF
32. Therapeutic and nontherapeutic research.
- Author
-
Lipsett MB
- Subjects
- Ethics, Medical, Helsinki Declaration, Nontherapeutic Human Experimentation, Research, Therapeutic Human Experimentation
- Published
- 1979
33. A radioimmunoassay of unconjugated oestradiol in urine.
- Author
-
Kono S, Loriaux DL, and Lipsett MB
- Subjects
- Animals, Charcoal, Chromatography, Thin Layer, Estrone, Female, Humans, Immune Sera, Male, Menstruation, Methods, Rabbits immunology, Radioimmunoassay, Serum Albumin, Bovine, Tritium, Estradiol urine
- Published
- 1974
- Full Text
- View/download PDF
34. Uterine estrogen and progesterone receptors in an estrogen- and progesterone- "resistant" primate.
- Author
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Chrousos GP, Brandon D, Renquist DM, Tomita M, Johnson E, Loriaux DL, and Lipsett MB
- Subjects
- Animals, Cytosol metabolism, Drug Resistance, Estradiol blood, Estradiol pharmacology, Female, Macaca fascicularis, Progesterone blood, Progesterone pharmacology, Saimiri, Receptors, Estrogen isolation & purification, Receptors, Progesterone isolation & purification, Uterus metabolism
- Abstract
The squirrel monkey, a New World primate, has elevated plasma estradiol and progesterone concentrations compared to those in the cynomolgus macaque, an Old World primate. We previously reported that uterine progesterone receptor concentrations examined in ovariectomized squirrel monkeys 2 days after estrogen treatment were about one eighth those in identically treated cynomolgus macaques. To examine this in greater detail, we gave estradiol (10 micrograms/kg X day) to ovariectomized squirrel and cynomolgus monkeys for various lengths of time (0, 2, 4, 7, and 14 days), followed by measurement of uterine estrogen and progesterone receptors and assessment of endometrial histology (including glycogen and peroxidase strains), vaginal histology, and cytology. Endometrial and vaginal morphologies showed adequate estrogen effects, as did glycogen and peroxidase stains. Two days of treatment were sufficient to induce both estrogen and progesterone receptors to maximal binding of [3H]moxestrol and [3H]R5020, respectively, in both species. Squirrel monkeys had about one third and one eighth the estrogen and progesterone uterine receptor concentrations, respectively, of cynomolgus monkeys. Receptor affinities in both species were similar. Neither [3H]moxestrol nor [3H]R5020 bound to uterine cytosols from untreated monkeys. We conclude that the increased plasma concentrations of estradiol and progesterone in the squirrel monkey compensate for the decreased estrogen and progesterone receptors in this species.
- Published
- 1984
- Full Text
- View/download PDF
35. Androgen binding proteins of testis, epididymis, and plasma in man and monkey.
- Author
-
Vigersky RA, Loriaux DL, Howards SS, Hodgen GB, Lipsett MB, and Chrambach A
- Subjects
- Animals, Dihydrotestosterone, Electrophoresis, Polyacrylamide Gel, Haplorhini, Humans, Isoelectric Focusing, Macaca mulatta, Male, Sex Hormone-Binding Globulin blood, Androgens, Carrier Proteins, Epididymis analysis, Sex Hormone-Binding Globulin analysis, Testis analysis
- Abstract
Androgen-binding protein (ABP) has been found in the cytosol of testicular and epididymal homogenates of several sub-primate species. In those species which had the plasma androgen binding protein, testosterone-estradiol-binding globulin (TeBG), ABP and TeBG were found to be physically similar. We investigated the possibility that ABP might exist in monkey and man using the cytosol of testicular and epididymal homogenates and aspirates obtained by direct micropuncture of the rete testis. In polyacrylamide gel electrophoresis, pH 7.8, testicular and epididymal cytosols of monkey and man were found to contain several binding proteins of different size and net charge that bind dihydrotestosterone. These binding proteins were either indistinguishable from TeBG or could be related to TeBG as size and/or charge isomers. No ABP was detectable in up to 200 mul of monkey rete testis fluid obtained by direct micropuncture, though ABP is detectable in as little as 5 mul of rat rete testis fluid. The data suggest that the ABP's detected in the testicular and epididymal cytosols in monkey and man represent isomeric forms of plasma TeBG, and their presence in testicular cytosol most likely derives from blood contamination.
- Published
- 1976
- Full Text
- View/download PDF
36. Progesterone resistance.
- Author
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Chrousos GP, MacLusky NJ, Brandon DD, Tomita M, Renquist DM, Loriaux DL, and Lipsett MB
- Subjects
- Androgens pharmacology, Animals, Cebidae, Drug Resistance, Endometrium analysis, Estradiol pharmacology, Estrogens pharmacology, Female, Follicle Stimulating Hormone blood, Genital Neoplasms, Female analysis, Humans, Kinetics, Luteinizing Hormone blood, Menstrual Cycle, Receptors, Estrogen analysis, Receptors, Progesterone analysis, Progesterone physiology
- Published
- 1986
- Full Text
- View/download PDF
37. Glucocorticoid receptor in polymorphonuclear leukocytes: a simple method for leukocyte glucocorticoid receptor characterization.
- Author
-
Murakami T, Brandon D, Rodbard D, Loriaux DL, and Lipsett MB
- Subjects
- Centrifugation, Density Gradient, Chromatography, Ion Exchange, Cytosol metabolism, Dexamethasone metabolism, Humans, In Vitro Techniques, Methods, Leukocytes metabolism, Neutrophils metabolism, Receptors, Glucocorticoid analysis, Receptors, Steroid analysis
- Published
- 1979
- Full Text
- View/download PDF
38. Research review at NIH.
- Author
-
Lipsett MB, Fletcher JC, and Secundy M
- Subjects
- Ethics, Medical, Humans, Informed Consent, United States, Ethical Review, Ethics Committees, Research, Human Experimentation, National Institutes of Health (U.S.), Peer Review
- Published
- 1979
39. The new world primates as animal models of glucocorticoid resistance.
- Author
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Chrousos GP, Loriaux DL, Tomita M, Brandon DD, Renquist D, Albertson B, and Lipsett MB
- Subjects
- Adrenal Glands analysis, Adrenocorticotropic Hormone blood, Aldehyde-Lyases metabolism, Aldosterone physiology, Animals, Aotus trivirgatus, Dexamethasone, Drug Resistance, Endorphins blood, Humans, Hypothalamo-Hypophyseal System physiology, Kidney analysis, Macaca fascicularis, Macaca mulatta, Monocytes analysis, Pituitary-Adrenal System physiology, Receptors, Glucocorticoid physiology, Receptors, Mineralocorticoid, Saimiri, Steroid 11-beta-Hydroxylase metabolism, Steroid 17-alpha-Hydroxylase, Steroid 21-Hydroxylase analysis, beta-Endorphin, Cebidae, Disease Models, Animal, Glucocorticoids physiology
- Abstract
Many New World primate species have greatly increased plasma cortisol concentrations, decreased plasma cortisol binding globulin capacity and affinity, marked resistance of the hypothalamic-pituitary-adrenal axis to suppression by dexamethasone, and no biological evidence of glucocorticoid excess. These primates also have high levels of circulating progesterone, estrogen, mineralocorticoid, androgen and vitamin D. The glucocorticoid target tissues that have been examined (circulating mononuclear lymphocytes and cultured skin fibroblasts) have normal concentrations of glucocorticoid receptors with decreased affinity for dexamethasone. Transformation of B-lymphocytes with the Epstein-Barr virus leads to glucocorticoid receptor induction that is less than that observed with cells from Old World primates. The receptor in these cells has a low affinity for dexamethasone. The low affinity leads to an increased loss of specific bound ligand during thermal activation. Meroreceptor generation is normal. The molecular weight of the receptor, determined by SDS-PAGE, is similar to that of Old World primates (approximately 92,000) and the activation pattern per se, examined in vitro by heating cytosol and performing phosphocellulose chromatography, appears similar to that of human controls. The ratios of nuclear to cytosolic hormone-receptor-complexes and of cytosolic activated to unactivated receptor complexes in intact cells are similar to Old World primates. Results from mixing studies do not support the hypothesis that a binding inhibitor(s) or a deficient cytosolic positive modifier(s) of binding underlies the findings in these primates. The New World primates, unlike men with the syndrome of primary cortisol resistance, have compensated for their condition with intra-adrenal and mineralocorticoid receptor adaptations. Thus, unlike Old World primates, cortisol in New World primates has only weak sodium-retaining potency because the aldosterone receptor has a low affinity for cortisol. The common element that would explain the apparent resistance to six steroid hormones in New World primates remains unknown.
- Published
- 1986
- Full Text
- View/download PDF
40. Do vitamins prevent neural tube defects (and can we find out ethically)?
- Author
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Lipsett MB and Fletcher JC
- Subjects
- Control Groups, Ethical Analysis, Ethicists, Female, Humans, Infant, Newborn, Patient Selection, Pregnancy, Research Subjects, Risk Assessment, Vitamins adverse effects, Clinical Trials as Topic, Ethics, Medical, Neural Tube Defects prevention & control, Pregnant Women, Vitamins therapeutic use
- Published
- 1983
41. Regulation of FSH secretion: use of hydroxyurea to deplete germinal epithelium.
- Author
-
Mecklenburg RS, Hetzel WD, Gulyas BJ, and Lipsett MB
- Subjects
- Animals, Follicle Stimulating Hormone blood, Luteinizing Hormone blood, Male, Mitosis, Radioimmunoassay, Rats, Time Factors, Follicle Stimulating Hormone metabolism, Hydroxyurea pharmacology, Testis cytology
- Abstract
Hydroxyurea, a chemotherapeutic agent that prevents mitosis by inhibiting DNA synthesis, was administered to adult male rats for 70 days. Plasma FSH and LH showed no systematic trend although severe germinal cell depletion was produced. These data suggest that the cell(s) of the seminiferous tubule involved in FSH regulation must be either the type A spermatogonium or the Sertoli cell.
- Published
- 1975
- Full Text
- View/download PDF
42. Why corticoids are effective against a wide variety of cancers.
- Author
-
Lipsett MB
- Subjects
- Glucocorticoids pharmacology, Humans, Hydrocortisone pharmacology, Immunity, Cellular drug effects, Neoplasms immunology, Prostaglandin Antagonists, Protein Binding, Receptors, Cell Surface, Glucocorticoids therapeutic use, Neoplasms drug therapy
- Published
- 1974
- Full Text
- View/download PDF
43. Adaptation of the mineralocorticoid target tissues to the high circulating cortisol and progesterone plasma levels in the squirrel monkey.
- Author
-
Chrousos GP, Loriaux DL, Brandon D, Shull J, Renquist D, Hogan W, Tomita M, and Lipsett MB
- Subjects
- Adrenal Cortex Hormones blood, Aldosterone metabolism, Animals, Electrolytes blood, Female, Hydrocortisone pharmacology, Macaca fascicularis metabolism, Male, Receptors, Glucocorticoid metabolism, Receptors, Mineralocorticoid, Renin blood, Transcortin blood, Cebidae metabolism, Hydrocortisone blood, Kidney metabolism, Progesterone blood, Receptors, Steroid metabolism, Saimiri metabolism
- Abstract
Many New World primate species have elevated circulating free plasma cortisol concentrations, target tissue resistance to cortisol, and no evidence of sodium retention. A representative New World primate, the squirrel monkey (Saimiri sciureus), has plasma cortisol concentrations above those necessary to cause complete suppression of the renin-angiotensin-aldosterone axis in an Old World primate, the cynomolgus monkey (Macaca fascicularis). Despite this, the arterial blood pressure as well as the plasma sodium, potassium, and bicarbonate levels of the squirrel monkey are similar to those of the cynomolgus monkey, and its plasma aldosterone concentrations are approximately 2-fold higher. These findings suggest that cortisol has minimal sodium-retaining effects in this species. Renal cytosol aldosterone receptor concentrations are about 2- to 3-fold lower in the squirrel monkey than in the cynomolgus, whereas the receptor affinities for [3H]aldosterone are similar in the two monkeys. Higher concentrations of cortisol are needed to displace [3H]aldosterone from the mineralocorticoid receptor in the squirrel monkey than from the renal receptor in the cynomolgus [apparent equilibrium dissociation constant (Ki) = 7.8 X 10(-7) vs. 2.9 X 10(-8) M, respectively]. In addition, in contrast to man and presumably other Old World primates, plasma aldosterone concentrations in the female squirrel monkey do not increase during the reproductive cycle or pregnancy when progesterone concentrations are 10- to 20-fold higher than those of the male or the reproductively quiescent female. This suggests that progesterone is a poor aldosterone antagonist in this species. We conclude that a low concentration of mineralocorticoid receptors in New World Primates is compensated for by higher aldosterone levels, with a concomitant increase in receptor occupancy. The salt-retaining potency of cortisol is low, presumably because of a decrease in the affinity of the aldosterone receptor for glucocorticoids in New World primates.
- Published
- 1984
- Full Text
- View/download PDF
44. Effects of catechol estrogen infusions upon gonadotropin and prolactin concentrations in men.
- Author
-
Merriam GR, Kono S, Keiser HR, Loriaux DL, and Lipsett MB
- Subjects
- Adult, Catecholamines metabolism, Dose-Response Relationship, Drug, Estrogens, Catechol metabolism, Humans, Male, Receptors, Estrogen metabolism, Estrogens, Catechol pharmacology, Gonadotropins, Pituitary blood, Prolactin blood
- Abstract
To study the effects of catechol estrogens upon gonadotropin secretion, 2-hydroxyestrone (2-OHE1) and 2-hydroxyestradiol (2-OHE2) were administered iv to young adult men in a range of doses for 4 days. Blood samples were obtained for plasma LH, FSH, and PRL at 20-min intervals for 6 h before and at the end of the infusion period. 2-OHE1 had no effect upon gonadotropins or PRL in doses up to 1.6 mg/day; at 3.2 and 6.6 mg/day, it produced a slight suppression of LH and FSH, with no change in PRL. 2-OHE2 was generally ineffective at 100 micrograms/day, but doses from 200-800 micrograms/day suppressed gonadotropins, without changes in PRL. These infusions elevated 2-OHE1 and 2-OHE2 plasma levels to values comparable to those measured in late pregnancy. There were no associated effects upon blood pressure and only minimal changes in urinary catecholamine excretion. No effects that could be interpreted as antiestrogenic were observed. These results are consistent with the hypothesis that circulating catechol estrogens behave as weak estrogens in men.
- Published
- 1981
- Full Text
- View/download PDF
45. Cortisol resistance in man.
- Author
-
Lipsett MB, Tomita M, Brandon DD, De Vroede MM, Loriaux DL, and Chrousos GP
- Subjects
- Adrenocorticotropic Hormone blood, Adult, Aldosterone urine, Alkalosis complications, Alkalosis genetics, Cell Transformation, Viral, Child, Circadian Rhythm, Corticosterone blood, Desoxycorticosterone blood, Dexamethasone, Drug Resistance, Herpesvirus 4, Human, Humans, Hypertension genetics, Hypokalemia genetics, Kinetics, Lymphocytes analysis, Male, Middle Aged, Molecular Weight, Pedigree, Pituitary-Adrenal System physiopathology, Hydrocortisone blood, Hypertension complications, Hypokalemia complications, Receptors, Glucocorticoid analysis
- Abstract
Primary cortisol resistance in man is a familial disease characterized by increased plasma cortisol concentrations, high urinary free cortisol excretion, a normal circadian pattern of cortisol secretion, resistance to adrenal suppression by dexamethasone and absence of the clinical stigmata of Cushing's syndrome or signs of adrenal insufficiency. In its severe form, hypertension and hypokalemic alkalosis are present, owing to increased secretion of the sodium-retaining corticoids, corticosterone and deoxycorticosterone. In subjects with a less severe resistance to cortisol, there are no clinical abnormalities and the disease is revealed only by detailed examination of several parameters of cortisol metabolism or by glucocorticoid receptor studies. In whole-cell glucocorticoid receptor assays (peripheral mononuclear leukocytes, fibroblasts, or B-lymphocytes transformed with the Epstein-Barr Virus) low receptor affinity for dexamethasone could be demonstrated conclusively only in the severely affected subject. When affected cells are transformed with the Epstein-Barr virus, receptor induction is less than that of normal cells. The decreased affinity of the receptor for its ligand is reflected in an increased rate of loss of specific bound ligand during thermal activation. The molecular weight of the receptor, determined by SDS-PAGE, is similar to that from normal cells (approximately 92,000). Only in the severely affected patient was the proportion of activated receptor remaining in the cytosol of thermally activated intact cells reduced. At saturating concentrations of dexamethasone, nuclear binding appears normal in cells from both the severe and the asymptomatic forms of this condition, providing an explanation for the apparently complete compensation of the target tissue resistance to glucocorticoids by the high plasma cortisol levels. The clinical manifestations of the disorder (hypertension, hypokalemia) can be corrected with high doses of dexamethasone (3mg/day).
- Published
- 1986
- Full Text
- View/download PDF
46. Low plasma levels of 2-hydroxyestrone are consistent with its rapid metabolic clearance.
- Author
-
Kono S, Brandon D, Merriam GR, Loriaux DL, and Lipsett MB
- Subjects
- Adolescent, Adult, Cross Reactions, Female, Humans, Hydroxyestrones immunology, Male, Menstruation, Metabolic Clearance Rate, Pregnancy, Radioimmunoassay, Time Factors, Estrone analogs & derivatives, Hydroxyestrones blood
- Abstract
Published plasma levels of the catechol estrogen 2-hydroxyestrone (2-OHE1) are comparable to those of estrone and estradiol. In light of the very high (40,000 L/d) metabolic clearance rate of 2-OHE1, these concentrations imply unreasonable production rates. We therefore re-examined plasma 2-OHE1 levels using a modified radioimmunoassay procedure. Plasma samples are extracted with ethyl acetate and passed over a short column of LH-20 Sephadex before equilibration with an antiserum directed against a 2-hydroxyestrone-17-(O-carboxymethyl)oxime-bovine serum albumin conjugate. Plasma 2-OHE1 concentrations are indistinguishable from blank (< 15 pg/ml) in men and non-pregnant women, but rise to approximately 200 pg/ml during pregnancy. These values for 2-OHE1 levels are consistent with the rapid metabolic clearance of this catechol estrogen.
- Published
- 1980
- Full Text
- View/download PDF
47. Hormones, nutrition, and cancer.
- Author
-
Lipsett MB
- Subjects
- Androstenedione metabolism, Anovulation complications, Breast Neoplasms etiology, Estrogens biosynthesis, Estrogens urine, Estrone biosynthesis, Female, Humans, Obesity metabolism, Uterine Neoplasms complications, Uterine Neoplasms metabolism, Hormones metabolism, Neoplasms etiology, Nutritional Physiological Phenomena
- Abstract
The effects of obesity on steroid metabolism in women with breast and uterine cancer have been considered. Obesity may increase plasma estrone by two mechanisms, a higher rate of secretion of the estrone precursor, androstenedione, and a higher rate of conversion of androstenedione to estrone. Obesity may alter routes of metabolism of androgens and estrogens. The excretion of specific urinary metabolites can therefore be altered by obesity alone. Thus, steroid indices of relative cancer risk or responsiveness must be constructed with due attention to obesity, one of many important variables.
- Published
- 1975
48. Production of testosterone by prostate and other peripheral tissues in man.
- Author
-
Lipsett MB
- Subjects
- Androgens blood, Androstane-3,17-diol biosynthesis, Androstenediols biosynthesis, Animals, Dehydroepiandrosterone biosynthesis, Dihydrotestosterone biosynthesis, Estradiol metabolism, Evaluation Studies as Topic, Female, Humans, Liver Circulation, Male, Metabolic Clearance Rate, Protein Binding, Receptors, Cell Surface, Secretory Rate, Serum Globulins metabolism, Prostate physiology, Testosterone biosynthesis
- Published
- 1975
- Full Text
- View/download PDF
49. Effects of cancers of the endocrine and central nervous systems on nutritional status.
- Author
-
Lipsett MB
- Subjects
- Calcitonin metabolism, Cholesterol deficiency, Diarrhea etiology, Gastrins metabolism, Gastrointestinal Hormones metabolism, Histamine Release, Humans, Hypercalcemia etiology, Neoplasms metabolism, Nutrition Disorders metabolism, Pellagra etiology, Peptides metabolism, Serum Albumin deficiency, Thyroid Hormones metabolism, Vasoactive Intestinal Peptide metabolism, Zollinger-Ellison Syndrome metabolism, Brain Neoplasms complications, Endocrine Glands metabolism, Neoplasms complications, Nutrition Disorders etiology
- Published
- 1977
50. Leydig cell function in men with disorders of spermatogenesis.
- Author
-
Ruder HJ, Loriaux DL, Sherins RJ, and Lipsett MB
- Subjects
- 17-alpha-Hydroxypregnenolone blood, Androstenols blood, Chorionic Gonadotropin pharmacology, Estradiol blood, Follicle Stimulating Hormone blood, Humans, Hydroxyprogesterones blood, Klinefelter Syndrome blood, Leydig Cells metabolism, Luteinizing Hormone blood, Male, Progesterone blood, Testosterone blood, Germ Cells abnormalities, Klinefelter Syndrome physiopathology, Leydig Cells physiopathology
- Published
- 1974
- Full Text
- View/download PDF
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