Showing papers on "Testosterone published in 1971"
TL;DR: Results from the studies indicate that changes in the metabolism of proteins lipids and carbohydrates take place in the testes under the control of hormones, but it may be that the observed biochemical changes are a reflection of the changes in cellular composition of testicular tissue rather than the result of metabolic changes within a specific cell type in response to the effect of a hormone.
Abstract: Studies of the hormonal control of the spermatogenic process are reviewed. Most of the investigations used the techniques of ablation and replacement therapy and were performed on the rat. Results from the studies indicate that changes in the metabolism of proteins lipids and carbohydrates take place in the testes under the control of hormones. However it may be that the observed biochemical changes which occur are a reflection of the changes in cellular composition of testicular tissue rather than the result of metabolic changes within a specific cell type in response to the effect of a hormone. A hypothesis concerned with the qualitative aspects of hormonal control of spermatogenesis in the rat has been formed. It is proposed that the multiplication and growth of gonocytes prenatally and in the first few days after birth and formation of type A spermatogonia are under the control of testosterone. The formation of type A and B spermatogonia and primary spermatocytes and progression of the meiotic prophase may be influenced by growth hormone. Reduction division is under control of testosterone. The early steps of spermatid formation may be under no hormonal control or may require testosterone while the late stages of spermatid maturation require the presence of FSH.
640 citations
TL;DR: The LH-RH preparation isolated has FSH-releasing hormone (FSH-RH) activity, which appears to be intrinsic to LH- RH, and appears to represent the hypothalamic hormone which controls the secretion of both LH and FSH from the pituitary.
585 citations
TL;DR: It is suggested that the steroid acts at or near the surface to cause the production of a second effector which, when accumulated to a sufficient level in the oocyte, induces the observable events associated with maturation.
378 citations
TL;DR: The steroid- and tissue-specificity of the cell-free systems strongly suggests that 5α-dihydrotestosterone plays a central role in the retention of an androgen receptor protein by prostate nuclei in vivo.
291 citations
TL;DR: It appears that the previously postulated end organ sensitivity, thought to account in, part for the occurrence and distribution of acne, may indeed exist and may be mediated by differential rats of conversion of testosterone to dihydrotestosterone in the skin.
273 citations
TL;DR: Testosterone production rates were found to be elevated in 13 consecutive hirsute women, confirming previous observations and it was apparent that, in 9 of the 13 women studied, the major source of androgen was ovarian.
Abstract: Testosterone production rates were found to be elevated in 13 consecutive hirsute women, confirming previous observations. To determine the origin of the excessive testosterone, percutaneous bilateral adrenal and ovarian vein catheterizations were performed, and effluent blood samples obtained for androgen measurement. Although physical examination and retrograde dye injections failed to reveal ovarian enlargement in any of these patients, testosterone and androstenedione concentrations were higher in ovarian effluents vs. adrenal venous samples. The relative contributions of adrenal and ovarian secretion, and precursor conversion to the total testosterone production rate, were estimated in each patient from kinetic considerations and by relating the effluent concentrations of testosterone and androstenedione to the cortisol secretion rate. From such calculations, it is apparent that, in 9 of the 13 women studied, the major source of androgen was ovarian (direct ovarian secretion of testosterone ...
201 citations
TL;DR: Free testosterone and 17β-hydroxysteroid indexes were succesively higher in children, females, hirsute females and...
Abstract: The relation of plasma free androgen levels to the pattern of sexual hair was studied. The possibility was explored that plasma free androgen levels in hirsute women might be increased by elevated concentrations of testosterone and other 17β-hydroxysteroids or by low “testosterone binding globulin” (TeBG). Nontestosterone 17β-hydroxysteroids are potentially androgenic, either inherently or by their ability to displace testosterone from binding sites. An index of the free plasma testosterone concentration was calculated as the product of the total concentration and the percentage of testosterone-3H free from TeBG as determined in diluted plasma by a charcoal absorption technique. An index of the free plasma 17β-hydroxysteroids3 and titer of TeBG (expressed as testosterone binding capacity) was obtained from the total concentration and percentage binding of 17β-hydroxysteroids to TeBG. Free testosterone and 17β-hydroxysteroid indexes were succesively higher in children, females, hirsute females and...
184 citations
TL;DR: The findings suggest that the capacity to form dihydrotestosterone in urogenital sinus and tubercle is not the result of androgen action but rather an inherent or obligatory property of the tissue and may fulfill in part the function of an initial androgen receptor in these organs.
Abstract: The rate of conversion of testosterone- l,2-3H to dihydrotestosterone-3H has been measured in a variety of tissues in rabbit embryos from 17 days of development to 3 days following birth and in rat embryos from 15 days of gestation to 4 days after delivery. In the rabbit embryo dihydrotestosterone formation was rapid only in the urogenital sinus and urogenital tubercle of both sexes at the earliest stages studied and was not measurable in wolffian and mullerian ducts until after gender identification was easily demonstrable. A similar pattern of development was observed in the rat embryo. These findings suggest that the capacity to form dihydrotestosterone in urogenital sinus and tubercle is not the result of androgen action but rather an inherent or obligatory property of the tissue and may fulfill in part the function of an initial androgen receptor in these organs. In contrast, in the mullerian and wolffian ducts the ability to form dihydrotestosterone appears to be acquired after the initial stages of...
173 citations
TL;DR: It was concluded that the peripherally active steroid dihydrotestosterone probably plays no role in the maintenance of sexual behavior and can be accumulated by brain and peripheral androgen-sensitive tissues.
164 citations
TL;DR: Prior to operation, the basal urinary excretion of estrone, estradiol and estriol was much increased above that of a normal man but it became normal after gonadectomy, and both before and after adrenal stimulation, the plasma androgens showed the pattern and concentrations of androstenedione.
Abstract: A patient with familial male pseudohermaphroditism was considered to be a normal female up to the time of puberty. At puberty, she had normal breast development but there was simultaneous enlargement of the clitoris and the body hair developed with a male distribution. The internal genitalia were male in type. Under basal conditions, the plasma concentration of testosterone (T) was low for a male subject but plasma levels of dehydroepiandrosterone (DHA) and dehydroepiandrosterone sulfate (DHAS) were 2–3 times higher than those of normal men. The plasma level of androstenedione (Δ) was 10 times normal. Following gonadectomy, the pattern of plasma androgens was similar to that of a normal woman. Prior to operation, the basal urinary excretion of estrone, estradiol and estriol was much increased above that of a normal man but it became normal after gonadectomy. Eighteen months after gonadectomy, both before and after adrenal stimulation, the plasma androgens showed the pattern and concentrations exp...
160 citations
TL;DR: It is suggested that dihydrotestosterone in the blood does not arise from direct secretion but may reflect events occurring in peripheral androgen target tissues.
Abstract: The source of plasma dihydrotestosterone (DHT) (17beta-hydroxy-5alpha-androstan-3-one) in humans has been investigated by infusing two potential peripheral precursors, testosterone (T) and androstenedione (A). Metabolic clearance rates (MCR), conversion ratios (CR), transfer constants (rho), and blood production rates (P(B)) were calculated. Plasma testosterone and dihydrotestosterone were measured by competitive binding techniques. The MCR(DHT) was 652 +/-35 (SD) liters/day in five males and 314 +/-63 (SD) liters/day in four adult females. In each individual, the MCR(DHT) was significantly lower than MCR(T) as predicted by testosterone-binding protein affinity studies. The P(B) (DHT) was 302 +/-65 (SD) mug/day in males and 56 +/-26 mug/day in females. Testosterone and androstenedione are precursors (prehormones) for plasma dihydrotestosterone. The conversion ratio CR(BB) (T-DHT), calculated as the ratio of counts per minute per liter of plasma of product to precursor after infusion of labeled precursor, was 5.6 +/-0.6 (SD)% (six subjects) in the male and 3.5 +/-0.4 (SD)% (four subjects) in the female. CR(BB) (A-DHT) after androstenedione infusion to three female subjects averaged 9.2%. No dihydrotestosterone back conversion was detected (< 0.2%). The transfer constants were [rho]BB(T-DHT), 3.9 +/-1.0% (male) and 1.7 +/-0.6% (female), and [rho]BB(A-DHT) average was 13.3% in three female subjects. Using either plasma testosterone and dihydrotestosterone values from our subjects and mean androstenedione values as reported in the literature, approximate contributions can be calculated. Testosterone conversion accounts for at least 70% of plasma DHT in the male, but less than 20% in the normal female. Androstenedione appears to be a major prehormone of plasma dihydrotestosterone accounting for at least two-thirds plasma dihydrotestosterone by peripheral conversion in adult females. In three normal women undergoing tubal ligation, there was an unimpressive gradient between ovarian vein and peripheral plasma dihydrotestosterone. It is suggested that dihydrotestosterone in the blood does not arise from direct secretion but may reflect events occurring in peripheral androgen target tissues.
TL;DR: Neonatally castrated male rats showed feminine behavior in- creases (compared with littermates castrated as adults) during testosterone-progesterone and estrogen treatments as well as during estrogen treatments.
Abstract: Neonatally castrated male rats showed feminine behavior in- creases (compared with littermates castrated as adults) during testosterone-progesterone and estrogen treatments as well as during estrogen-
TL;DR: The incorporation of radioactivity by rat prostate has been measured following administration of seven tritium-labeled natural androgens to separate groups of castrated functionally hepatectomized rats and dihydrotestosterone consistently was found to be the major metabolite.
Abstract: The incorporation of radioactivity by rat prostate has been measured following administration of seven tritium-labeled natural androgens to separate groups of castrated functionally hepatectomized rats. In addition a study has been made of the identity and subcellular localization of metabolites formed from each steroid. With every androgen tested radioactivity was detected in cytoplasmic and nuclear fractions at intervals ranging from 5 min to 1 hour after the administration of the hormone. Highest levels of nuclear radioactivity were achieved with testosterone, dihydrotestosterone and androstanediol; intermediate levels with androstanedione, androstanedione, and androsterone; a low level with dehydroepiandrosterone. Every androgen gave rise to several metabolites in prostatic cytoplasm and invariably one of these was dihydrotestosterone. In nuclei dihydrotestosterone consistently was found to be the major metabolite. There was a striking absence of any other significant nuclear product except for testos...
TL;DR: A review of actions of vertebrate sex hormones is presented and influences of sex hormones on structure, metabolism, and functions of reproductive organs are examined.
Abstract: A review of actions of vertebrate sex hormones is presented. The main topics of discussion are: 1) intracellular proteins binding sex hor mones and their metabolites (estrogen uptake by intact normal cells; upt ake of estrogens by mammary gland and by mammary and other tumors; ster eospecific estrogen-binding proteids in responsive tissues; uptake of androgens by animal cells and formation of 5alpha-androstane and other derivatives; 5alpha-dihydrotestosterone-binding proteids; disposition of progesterone in various tissues); 2) testicular feminization syndrome; 3) effects of sex hormones on organ cultures with comments on deoxyribonucleic acid synthesis and cell division in relation to tissue growth; 4) estrogen-mediated pyridine nucleotide transhydrogenase reactions; 5) intracellular "2nd messengers" and sex hormone action (polyamines); 6) physiological actions of 5beta-hydrogenated steroid metabolites and effects of sex hormones on erythropoiesis; 7) influences of sex hormones on structure metabolism and functions of reproductive organs (ribonucleic acid - RNA - and protein synthesis; RNA preparations and genital tissue growth; androgens and cation-activated adenosinetriphosphatase reactions; uptake of glucose and glycogen synthesis; mitochondrial reactions; gonadal hormones and sebaceous glands);
TL;DR: Androstanolone was more active than testosterone and also provoked epithelial hyperplasia which was seen only after high doses of testosterone, indicating that testosterone action may be related to its conversion to different active metabolites, and particularly to androStanolone and 3β-androstanediol.
TL;DR: Plasma LH increased during T3 treatment, indicating that it is the non-TeBG-bound testosterone that determines LH release, and it is most likely that hyperthyroidism increased the rate of metabolism of estradiol.
Abstract: Five normal men were made clinically hyperthyroid by administration of T3, 300 μg daily for three weeks. In 3 men, estradiol metabolic clearance rates and plasma concentration of testosterone-estradiol binding globulin (TeBG) were measured during the control periods, during fluoxymesterone administration, and during hyperthyroidism. Plasma LH and testosterone concentrations were determined throughout all studies in 5 men. Treatment with T3 caused a 7–8 fold increase in TeBG; a 2–3 fold increase in plasma testosterone; no change in CBG, and no change in in 2 patients and a 25% decrease in the third. The marked rise in TeBG during T3 treatment was not accompanied by a corresponding large fall in hence it is most likely that hyperthyroidism increased the rate of metabolism of estradiol. In spite of a 2–3 fold increase in plasma testosterone, plasma LH increased during T3 treatment, indicating that it is the non-TeBG-bound testosterone that determines LH release. The plasma half-life of TeBG was esti...
TL;DR: Aggressive behaviour in unisexual pair encounters between adult male hamsters decreases after castration and is restored by injections of either testosterone propionate or oestradiol benzoate, indicating that progesterone, in the presence of oestrogen, reduces female aggression.
TL;DR: Testosterone propionate was the only steroid which restored the ejaculatory pattern to castrated males and all of the hormones induced the growth of penile "spines", so the failure of dihydrotestosterone propIONate or dihydotestosterone to restore masculine behavior to castrating males was probably not due to an inadequate action of these hormones on the penis.
Abstract: Free and propionate forms of dihydrotestosterone were compared with testosterone propionate to evaluate their ability to restore masculine behavior in castrated rats. Induction of the growth of penile "spines" in castrated adult rats by testosterone propionate and dihydrotestosterone propionate was examined. Testosterone propionate was the only steroid which restored the ejaculatory pattern to castrated males. All of the hormones induced the growth of penile "spines". Therefore the failure of dihydrotestosterone propionate or dihydrotestosterone to restore masculine behavior to castrated males was probably not due to an inadequate action of these hormones on the penis. All hormones caused significant gains in body weight with testosterone propionate causing the highest gain. Testosterone propionate and dihydrotestosterone propionate caused a significant decrease in testicular weight in immature rats. Testosterone propionate caused a considerable increase in seminal vesicle weight much larger than that induce by dihydrotestosterone propionate. Human chorionic gonadotropin (HCG) treatment seemed to stimulate release of testosterone from the testes of immature animals.
TL;DR: It was determined that a major fraction of plasma dihydrotestosterone was derived from these plasma precursors rather than from glandular secretion.
Abstract: Dihydrotestosterone metabolism was studied with a constant infusion technique in three men, three women, five hirsute women, and four estrogen-treated hirsute women. The mean dihydrotestosterone metabolic clearance rate was higher in men (336 liters/24 hr per m(2) [range, 239-448]) than in women (153 liters/24 hr per m(2) [range, 108-184]). The metabolic clearance rates in hirsute patients were intermediate between those men and women and were decreased by estrogen treatment. These observations demonstrate similarities in the metabolic rates of testosterone and dihydrotestosterone. The conversion of plasma testosterone and androstenedione to dihydrotestosterone was studied in men and hirsute women. Approximately 4 and 2% of plasma testosterone and androstenedione, respectively, were converted to plasma dihydrotestosterone in both groups. From these observations it was determined that a major fraction of plasma dihydrotestosterone was derived from these plasma precursors rather than from glandular secretion. Both 5alpha-androstan-3alpha,17beta-diol (3alpha-diol) and 5alpha-androstan-3beta,17beta-diol (3beta-diol) were identified in plasma during dihydrotestosterone and testosterone infusions. The conversion ratio of dihydrotestosterone to 3alpha-diol (C(BB) (DHT-3alpha)) was greater than the conversion ratio to the 3beta-isomer (C(BB) (DTH-3beta)) in all the patients studied. Both C(BB) (DHT-3alpha) and C(BB) (DHT-3beta) were higher in men (mean values of 0.151 [range, 0.110-0.222] and 0..031 [range, 0.022-0.042]) than in women (means of 0.044 [range, 0.037-0.048] and 0.012 [range 0.010-0.013]). A smaller fraction of testosterone was converted to 3alpha-diol and 3beta-diol.
TL;DR: The concentration in testicular plasma increased in the late stages of maturation; this observation is consistent with the conclusion based on in vitro incubations that 11β-hydroxytestosterone is a precursor of 11-ketotestosterone in testis.
TL;DR: The effects of an ethinyl testosterone analogue, 17α-pregn-4-en-20-yno-(2,3-d) isoxazol-17-ol (Danazol), on the pituitary-testicular function of normal males are described.
Abstract: The effects of an ethinyl testosterone analogue, 17α-pregn-4-en-20-yno-(2,3-d) isoxazol-17-ol (Danazol), on the pituitary-testicular function of normal males are described. This compound has been shown to have an impeded androgenic effect in hypophysectomized male rats but no estrogenic or progestational activity. When administered to adult human males in doses of 200 or 600 mg daily, Danazol produced decreases in plasma levels of testosterone (T) and androstenedione (A) which were dose related. Changes in plasma steroid concentration were associated with symptoms of androgen withdrawal. Despite the marked reduction in plasma T, serum LH titers remained unchanged with the low dose but declined with the high dose schedule. Urinary FSH excretion titers decreased only during the high dose schedules of Danazol. HCG restored T to normal levels in the Danazol treated men within 4 days. Clomiphene administration produced increased serum LH and T levels in Danazol treated men as well as in untreated men....
TL;DR: The sexual dimorphism in the embryonic development of mouse mammary glands is caused by their suppression in males and not by their stimulation in female embryos.
Abstract: Factors underlying the sexual dimorphism in the embryonic development of mouse mammary glands were analysed in vitro and the following results were obtained:
1. Mammary gland rudiments of 13-day male embryos, explanted immediately before the onset of their regression, were perfectly capable of developing into female-type glands in vitro . Even some of the glands of 14-day male embryos, where the regression process had already begun, recovered after explantation and underwent female-type morphogenesis.
2. Combined explantation of 13-day testes with mammary rudiments of female embryos of 12–14 days gestation resulted in male-type regression of the glands.
3. The addition of testosterone to the culture medium caused a similar regression of explanted (female) mammary-gland rudiments. The minimal effective concentration of the hormone was 10−9m, or 0·00029 μg/ml.
4. Cultured mammary rudiments of 15-day female embryos were no longer responsive to the presence of testis explants. They failed to undergo regression and continued their development in vitro .
From these results the following conclusions were drawn:
( a ) The sexual dimorphism in the embryonic development of mouse mammary glands is caused by their suppression in males and not by their stimulation in female embryos.
( b ) The androgenic hormones in male foetuses are solely responsible for the regression of the mammary rudiments. They exert their effect directly on the gland without the need for involvement of other endocrine organs.
( c ) The genetic sex of the gland itself has no influence on its developmental capacities as: (i) glands of male embryos are able to develop in the absence of androgens, and (ii) glands of female embryos undergo typical male-type regression in vitro when exposed to the presence of foetal testes or of testosterone.
TL;DR: The hypothesis that testosterone, or one of its metabolites, is the defeminizing agent in the neonatal male mouse is supported.
Journal Article•
TL;DR: The effect of testosterone on the incorporation in vitro of 32P from [γ-32P]-ATP into non-histone phosphoproteins of nuclei from castrated rats could be demonstrated as early as 30 min following a single injection of testosterone propionate.
Abstract: 32P from [γ-32P]-ATP was rapidly incorporated into phosphoproteins of rat ventral prostate nuclei in vitro . At least 80% of the radioactivity (expressed per milligram of protein) was present in the non-histone phosphoproteins. The incorporation of 32P into phosphoproteins of nuclei isolated from orchiectomized rats was reduced greatly compared with nuclei isolated from orchiectomized rats treated with testosterone propionate or from normal control rats. The effect of testosterone on the incorporation in vitro of 32P from [γ-32P]-ATP into non-histone phosphoproteins of nuclei from castrated rats could be demonstrated as early as 30 min following a single injection of testosterone propionate. This effect could be explained in terms of increased activity of protein phosphokinase(s) in the nuclei. A possible role of nuclear protein phosphokinase(s) and the phosphorylation of non-histone phosphoproteins in the events related to the control of gene action in the prostate in response to testosterone is suggested.
ACKNOWLEDGMENTS We thank Mr. C. Riggs for his help in these experiments. One of us (H. I.) wishes to thank the Fogarty International Center for the award of a Visiting Fellowship.
TL;DR: It is proposed that the androgen insensitivity in Tfm/Y is related to the inability of these animals to concentrate androgens at active sites in the nucleus.
TL;DR: This 13-yr-old boy's puberty was manifested by the development of male secondary sexual characteristics and marked gynecomastia, and there was a rise in plasma testosterone following human chorionic gonadotropin administration, suggesting that the pubertal age was reached.
Abstract: This is the first report of a child with the 3β-hydroxysteroid dehydrogenase (3β-HSD) defect to have reached a pubertal age. This 13-yr-old boy's puberty was manifested by the development of male secondary sexual characteristics and marked gynecomastia. Clinical support for the diagnosis consisted of his marked salt-wasting, hypospadias and family history of 2 infants who died with congenital adrenal hyperplasia and ambiguous external genitalia. Laboratory support for the diagnosis consisted of greatly elevated plasma pregnenolone,6 17-OH-pregnenolone and DHEA, as well as high urinary pregnenetriol and DHEA. The paradoxical presence of progesterone in blood and of pregnanetriol, androsterone and etiocholanolone in the urine of this and other patients probably results from peripheral conversion of pregnene compounds by liver 3β-HSD enzymes to pregnane compounds. In this patient there was a rise in plasma testosterone following human chorionic gonadotropin administration, suggesting that the pubert...
TL;DR: The sex-limited protein (Slp) antigen of the mouse is first detected in the serum of strain DBA/2J males at 5–6 weeks of age and reaches full adult levels by 10 weeks, when it is dependent on both the proper genotype and the presence of male hormone.
Abstract: The sex-limited protein (Slp) antigen of the mouse is first detected in the serum of strain DBA/2J males at 5–6 weeks of age and reaches full adult levels by 10 weeks. This antigen is normally absent in females. Immature DBA/2J males castrated at 3 1/2 weeks of age failed to develop Slp antigen, while DBA/2J females treated with testosterone propionate starting at 3 1/2 weeks developed normal adult male levels of Slp antigen. Similar hormone-influenced effects were demonstrated in adult males and females of the same strain. Experiments indicated that testosterone does not act directly in the serum to expose Slp antigenic sites. Testosterone treatment of both males and females of strain C57BL/10JSf, which does not carry the gene for the presence of the Slp antigen, failed to stimulate the appearance of the antigen. Thus, the presence of Slp antigen in the serum is dependent on both the proper genotype and the presence of male hormone.
TL;DR: Diurnal variation, with a morning peak, in plasma testosterone—the most potent naturally occurring androgen—is demonstrated in man and the origin is not known.
Abstract: IN man, several studies1,2 have demonstrated diurnal variation, with a morning peak, in plasma testosterone—the most potent naturally occurring androgen. The origin of this variation is not known.
TL;DR: The fractional recovery of rat prostatic nuclei isolated by centrifugation differed markedly at various phases of androgen-induced growth, with the lowest nuclear volumes observed in the prostates of castrated animals and these changes could be reversed by androgen therapy.
TL;DR: The submandibular and inguinal glands seemed respectively the most and least sensitive to estradiol; a low dose of progesterone failed to increase gland weight or secretory activity in castrated animals and progester one significantly modified the suppressive action ofEstradiol on gland weight.
Abstract: At The University in Sheffield England researchers studied the effects of various steroid hormones on rabbit apocrine glands. The rabbits specialized apocrine glands occur in the submandibular (chin) inguinal and anal regions; this study considers glands from all 3 regions. Activity was judged through histological observation; tubules/microscope field were counted and the heights of the secretory epithelia of 30 tubules in each gland section were measured. Prepubertal castration in males and subsequent androgen replacement indicated androgens play a major role in the control of gland weight and activity. However further experiments suggested the glands remain unstimulated by extratesticular androgens of adrenal origin. Both in intact male animals and in castrated males given an implant of exogenous testosterone estradiol markedly decreased gland weight and secretory activity. The submandibular and inguinal glands seemed respectively the most and least sensitive to estradiol. A low dose of progesterone failed to increase gland weight or secretory activity in castrated animals. On the other hand progesterone significantly modified the suppressive action of estradiol on gland weight; the effect was especially marked in the inguinal region.