Showing papers on "Testosterone published in 1980"
TL;DR: A morphological sex difference in hormone-sensitive motoneurons that are probably involved in the sexually dimorphic copulatory behavior of the rat are demonstrated.
Abstract: The fifth and sixth lumbar segments of the rat spinal cord were found to contain a sexually dimorphic nucleus, the spinal nucleus of the bulbocavernosus (SNB). The SNB, which contains motoneurons innervating perineal striated muscles in normal male rats, is adiminished or absent in normal females and in males with a genetic mutation rendering them insensitive to androgens. The presence of the nucleus is apparently not dependent on genetic sex, but on the action of androgens. The motoneurons of the adult male SNGH accumulate hormone after systemic injections of radioactive testosterone or dihydrotestosterone, but not estradiol, and the SNB motoneurons accumulate more of the injected androgens than do other motoneurons in the same spinal segments. These results demonstrate a morphological sex difference in hormone-sensitive motoneurons that are probably involved in the sexually dimorphic copulatory behavior of the rat.
597 citations
TL;DR: Dispersed cells from whole testes or from isolated interstitial tissue of mature rats, yielded two distinct populations of Leydig cells when subjected to centrifugation in a 0-40% metrizamide gradient, and binding of 125I-labeled hCG by each population of cells indicated a single class of binding sites with the same high binding affinity.
Abstract: Dispersed cells from whole testes or from isolated interstitial tissue of mature rats, yielded two distinct populations of Leydig cells when subjected to centrifugation in a 0-40% metrizamide gradient. One population (I) was found in a fractions with a density of 1.085-1.117 g/cm3, and the other population (II) was found in fractions with a density of 1.128-1.145 g/cm3. Binding of 125I-labeled hCG by each population of cells indicated a single class of binding sites with the same high binding affinity and similar concentrations of binding sites per Leydig cell. Testosterone production per fmol gonadotropin receptor site in the absence of gonadotropin stimulation was similar for cells of each population. However, when cells from each population were incubated with increasing concentrations of hCG or dibutyryl cAMP, only Leydig cells from population II exhibited a marked increase in testosterone production. The low responsiveness of Leydig cells in population I did not appear to be a result of either damage to these cells or inhibition by non-Leydig interstitial cells in population I.
402 citations
TL;DR: It is suggested that factors other than aging might have influenceed the data previously reported, and that aging per se need not be associated with altered sex steroid levels in the human male.
Abstract: Although alterations of circulating sex steroids have been reported in aging men, it is not known to what extent reported changes may represent effects of variables other than aging. We have measured sex hormone levels, serum binding, the testosterone (T) response to hCG, and basal LH levels in 69 male volunteers, aged 25–89 yr, without alcoholism, obesity, chronic illness, or severe prostatic disease, and not using potentially interfering medications. In our study there was no effect of age on serum T, 5αdihydrotestosterone, estrone, or estradiol. Binding of T to Tbinding globulin increased slightly with age, but not enough to decrease the free T index (fraction free × T concentration). Basal serum LH rose significantly. The T response to hCG suggested a somewhat diminished Leydig cell reserve with age, a conclusion consistent with the LH elevation. Our failure to detect the decreased T and free T index or increased estrogens reported by others could reflect afternoon rather than morning sampling, but is...
359 citations
TL;DR: It is possible to provide a working hypothesis as to the pathogenesis of prostatic hyperplasia and several potential medical treatments may be feasible that do not involve a chemical castration.
329 citations
TL;DR: Morphometric analysis of Leydig cells in mature normal rats was carried out on tissue fixed by perfusion with buffered glutaraldehyde, and embedded in glycol methacrylate for light microscopy and in Epon for electron microscopy to obtain quantitative information about rat LeydIG cells and their organelles that might be correlated with pertinent physiological and biochemical data available either now or in the future.
Abstract: Leydig cells are thought to be the source of most, if not all, the testosterone produced by the testis. The goal of this study was to obtain quantitative information about rat Leydig cells and their organelles that might be correlated with pertinent physiological and biochemical data available either now or in the future. Morphometric analysis of Leydig cells in mature normal rats was carried out on tissue fixed by perfusion with buffered glutaraldehyde, and embedded in glycol methacrylate for light microscopy and in Epon for electron microscopy. In a whole testis, 82.4% of the volume was occupied by seminiferous tubules, 15.7% by the interstitial tissue, and 1.9% by the capsule. Leydig cells constituted 2.7% of testicular volume. Each cubic centimeter (contained approximatelyy 1 g) of rat testis contained about 22 million Leydig cells. An average Leydig cell had a volume of 1,210 micron3 and its plasma membrane had a surface area of 1,520 micron2. The smooth endoplasmic reticulum (SER), the most prominent organelle in Leydig cells and a major site of steroidogenic enzymes, had a surface area of approximately 10,500 micron2/cell, which is 6.9 times that of the plasma membrane and is 60% of the total membrane area of the cell. The total surface area of Leydig SER per cubic centimeter of testis tissue is approximately 2,300 cm2 or 0.23 m2. There were 3.0 mg of Leydig mitochondria in 1 g of testis tissue. The average Leydig cell contained approximately 622 mitochondria, measuring on the average 0.35 micron in diameter and 2.40 micron in length. The mitochondrial inner membrane (including cristae), another important site of steroidogenic enzymes, had a surface area of 2,920 micron2/cell, which is 1.9 times that of the plasma membrane. There were 644 cm2 of inner mitochondrial membrane/cm3 of testis tissue. These morphometric results can be correlated with published data on the rate of testosterone secretion to show that an average Leydig cell secretes approximately 0.44 pg of testosterone/d or 10,600 molecules of testosterone/s. The rate of testosterone production by each square centimeter of SER is 4.2 ng/d or 101 million molecules/s: the corresponding rate for each square centimeter of mitochondrial inner membrane is 15 ng testosterone/d or 362 million molecules/s.
310 citations
TL;DR: Electrophysiological field potentials from hippocampal slices of rat brain show sex-linked differences in response to 1 X 10(-10)M concentrations of estradiol and testosterone added to the incubation medium.
Abstract: Electrophysiological field potentials from hippocampal slices of rat brain show sex-linked differences in response to 1 X 10(-10)M concentrations of estradiol and testosterone added to the incubation medium. Slices from male rats show increased excitability to estradiol and not to testosterone. Slices from female rats are not affected by estradiol, but slices from female rats in diestrus show increased excitability in response to testosterone whereas slices from females in proestrus show decreased excitability.
309 citations
TL;DR: Two novel perspectives are provided on the control of reproductive hormone secretion in male rats: environmental cues, which males learn to associate with sexual activity, induce the secretion of hormones that regulate pituitary-testis function, and classical conditioning may be used as a noninvasive method to evoke functional alterations in the release of luteinizing hormone.
Abstract: A classical conditioning paradigm was used to demonstrate that male rats can learn to secrete luteinizing hormone and testosterone in anticipation of sexual activity. Sexually naive males were exposed to a neutral stimulus and then to a sexually receptive female once daily. After exposure to the paired stimuli for 14 trials, the neutral stimulus was as effective as the female in triggering luteinizing hormone and testosterone secretion. These findings provide two novel perspectives on the control of reproductive hormone secretion in male rats: (i) environmental cues, which males learn to associate with sexual activity, induce the secretion of hormones that regulate pituitary-testis function, and (ii) classical conditioning may be used as a noninvasive method to evoke functional alterations in the secretion of luteinizing hormone and presumably the neuroendocrine pathways that mediate its release.
265 citations
TL;DR: Androgens have been tried in a variety of clinical situations other than male hypogonadism in the hopes that the nonvirilizing actions would outweigh any detectable side effects, and the only disorders in which a salutary effect has been documented are hereditary angioneurotic edema and some patients with anemia due to failure off the bone marrow.
Abstract: Because testosterone is rapidly metabolized by the liver, it is necessary either to administer androgens by injection in the form of testosterone esters that are absorbed slowly into the circulation or to administer by mouth derivatives that are slowly metabolized by the liver. The later derivatives, however, have deleterious side effects that limit their usefulness. Long-acting parenteral androgen esters are the treatment of choice in the replacement therapy of male hypogonadism. Because these esters must be hydrolyzed to the free hormone prior to exerting their cellular actions the effectiveness of therapy can be monitored by following plasma testosterone levels. All known effects of the endogenous hormone can be duplicated except for the induction and maintenance of normal spermatogenesis. Androgens have been tried in a variety of clinical situations other than male hypogonadism in the hopes that the nonvirilizing actions would outweigh any detectable side effects. The only disorders in which a salutary effect has been documented are hereditary angioneurotic edema and some patients with anemia due to failure off the bone marrow.
246 citations
TL;DR: Quantification of three steroids (T, delta 4, and dihydrotestosterone) in umbilical arterial and venous plasma from five male and nine female fetuses revealed significant arterial/venous differences only for T in males (arterial greater than venous).
Abstract: Male rhesus monkey fetuses have significantly more testosterone (T) in their circulation than females on days 35–50 of gestation (P < 0.01; n = 6 males and 6 females). However, we found no sex differences for androstenedione (Δ4). T concentrations remained significantly higher in male fetuses than in females later in gestation, e.g. days 79–84, 100–133, and 140–160. Levels of Δ4 differed between the sexes only on days 79–84, and dihydrotestosterone concentrations were significantly higher in male fetuses than in females on days 100–133 and 140–163. The fact that Δ4 concentrations were not different betweenthe sexes at the earliest period studied (days 35–50) indicatesthat systemic concentrations of this hormone in the fetus probably are not important for sexual differentiation, especially of the central nervous system. Quantification of three steroids (T,Δ, and dihydrotestosterone) in umbilical arterial and venous plasma from five male and nine female fetuses (days 35–100) revealed significant arterial/ve...
212 citations
TL;DR: A reliable method which permits the simultaneous measurement of pregnenolone, progesterone, 17-OH-progesterone, androstenedione, testosterone, dihydrotestosterone, estrone and estradiol in rat testis is described.
181 citations
TL;DR: The presence of Gn RH receptors in the testis indicates that these sites mediate the direct inhibitory actions of GnRH agonists upon testicular endocrine function.
Abstract: Agonist analogs of gonadotropin-releasing hormone (GnRH) have been shown to exert antigonadal effects in male and female animals. In hypophysectomized male rats treated with follicle-stimulating hormone, administration of a potent GnRH agonist caused depletion of luteinizing hormone and prolactin receptors and marked suppression of serum testosterone levels. The possibility that such direct effects of GnRH agonists on testicular function could be expressed through specific receptors located in the interstitial cells of the testis was supported by the selective concentration of a 125I-labeled GnRH agonist by the testis in vivo. Specific receptors for the releasing hormone were demonstrated in testis particles and dispersed interstitial cells by direct binding analysis with the 125I-labeled GnRH agonist. The binding affinity (Ka = G X 10(9) M-1) and peptide specificity of the testicular GnRH binding sites were similar to those of anterior pituitary and ovarian GnRH receptors. The presence of GnRH receptors in the testis indicates that these sites mediate the direct inhibitory actions of GnRH agonists upon testicular endocrine function.
TL;DR: The background of the majority of the anovulatory cycles seems to be a physiological variant of the pattern seen in the polycystic ovary syndrome: the levels of testosterone, androstenedione and LH were increased in anovulation cycles compared to ovulatory ones.
Abstract: Pubertal development of 200 normal girls, 7--17 years of age, was investigated in a partly longitudinal manner with two examinations 1.5 years apart. Samples from postmenarchal girls were taken on days 6--9 and 20--23 of the menstrual cycle. Serum pregnenolone, progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone, 5 alpha-dihydrotestosterone, androsterone, oestradiol and cortisol as well as ACTH, FSH, LH and prolactin were measured radioimmunologically and were related to bone age, breast and pubic hair developmental stages, and gynaecological age. In the samples of premenarchal girls as well as the follicular phase of postmenarchal girls the concentration of all the steroids increased with age. Of all the steroids measured, serum dehydroepiandrosterone and pregnenolone displayed the earlier increase, from the youngest age group of 7.5 years onwards. Serum oestradiol testosterone and androstenedione in creased rapidly from the bone age group of 9.5 years (subjects 9.0--9.9 years of age) onwards, in close association with the appearance of the first physical signs of puberty. A marked increase in these three steroids continued until 13.5 years, the age at which menarche took place. Menarche was followed by a plateau of 1--2 years duration and then a second increase took place up to the two oldest age groups (17.5 and 18.5 years bone age), a trend seen in the follicular phase levels of all the steroids measured. The 5 alpha-dihydrotesterone/testosterone ratio decreased with increasing testosterone concentration. Serum oestradiol, testosterone, androstenedione, dehydroepiandrosterone and FSH showed no overlapping in the 2.5--97.5% range of concentrations and androsterone and LH in the 16--84% range between prepubertal and postmenarchal subjects. Pregnenolone, progesterone, 17-hydroxyprogesterone, 5 alpha-dihydrotesterone, cortisol, ACTH and prolactin overlapped even in the 16--84% range between these two groups of subjects. In postmenarchal girls, about 80% of the cycles were anovulatory in the first year after menarche, 50% in the third and 10% in the sixth year. The background of the majority of the anovulatory cycles seems to be a physiological variant of the pattern seen in the polycystic ovary syndrome: the levels of testosterone, and androstenedione and LH were increased in anovulatory cycles compared to ovulatory ones.
TL;DR: It is implied that the changes in plasma hormone levels depend more on the intensity of the exercise than on its duration, and the activity of the pituitary-adrenocortical system appears to be a good indicator of the effort expended during the exercise.
Abstract: Changes in plasma cortisol, androstenedione, testosterone and luteinizing hormone (LH) were measured in five young male sprinters after maximal short-term running and in five young male long-distan...
TL;DR: In studies designed to elucidate morphogenetic mechanisms involved in the neurogenesis of sexual differentiation of the brain, estradiol or testosterone was added to organotypic cultures of the newborn mouse hypothalamus and preoptic area, apparent hormonal specificity suggests that the neuritic response may be a component of sexual differentitation.
TL;DR: The data demonstrate that PRL measured in patients with advanced renal failure is biologically active and that hyperprolactinemia is one of the major factors in the hypogonadism of these patients.
TL;DR: Analysis of the relationship between body build and hormone levels indicated that estradiol levels were highest in gynandromorphic men and lowest in mesomorphic men, as estimated by testosterone levels and the free testosterone index.
Abstract: Basal plasma levels of testosterone, dihydrotestosterone, estradiol, and gonadotropins and testosterone-binding capacity (percent radioactive testosterone bound to protein) were measured in healthy carefully screened young (31–44 yr old; n = 44) and older (64–88 yr old; n = 42) male participants in the Normative Aging Study of the V.A. There was no statistically significant effect of age on testosterone [younger group, 4.16 ± 0.27 (SEM) ng/ml; older group, 4.62 ± 0.32 (SEM) ng/ml] or the free testosterone index [younger group, 2.05 ± 0.14 (SEM) ng/ml; older group, 1.76 ± 0.11 (SEM) ng/ml]. The testosterone-binding capacity was higher in the older group (younger group,50.10 ± 1.18% (SEM); older group, 60.10 ± 1.18% (SEM); P < 0.001). Of the two products of testosterone metabolism studied, estradiol did not change with age,while dihydrotestosterone was lower [younger group, 0.25 ± 0.02 (SEM) ng/ml; older group, 0.20 ± 0.01 (SEM) ng/ml; P = 0.03] in the older group. FSH levels were increased among the older ...
TL;DR: Two experiments provide further evidence for an aromatization theory of quail copulation by administering Silastic tubing containing testosterone propionate, testosterone, androstenedione and having no effect on EB-stimulated copulation.
TL;DR: Low dose pulsatile administration of GnRH to patients with isolated gonadotropin deficiency results in changing patterns of hormone secretion similar to those seen during puberty, and exaggerated pituitary sensitivity to GnRH may indicate previous rather than current secretion of Gn RH.
Abstract: Patients with isolated gonadotropin deficiency were studied to determine whether pulsatile low dose gonadotropin- releasing hormone (GnRH) could induce the hormonal changes seen during normal puberty. Four male and two female patients with immature responses to a standard GnRH test (2.5 μg/kg) were given GnRH (0.025 μg/kg) iv every 2 h for 5 days. FSH responses varied between the sexes, and FSH concentrations in males rose continuously to 17.2 ± 4.7 mlU/ml on day 5. In the females, FSH peaked at 13.8 and 15.8 mlU/ml on days 3–4 and then declined. The males showed increasing and the females decreasing incremental FSH responses to GnRH. LH concentrations and incremental responses to GnRH rose throughout the study in both sexes. Plasma testosterone rose slightly in the males to 0.7 ± 0.2 ng/ml (P < 0.05), but in females estradiol increased to follicular range concentrations of 128 and 102 pg/ml. Standard GnRH tests on day 6 revealed maturation of gonadotropin responses in all patients. After termination of p...
TL;DR: In vitro studies demonstrated that treatment with the GnRH agonist in vivo inhibited both basal and hCG-stimulated androgen production in FSH-primed immature hypophysectomized rats and inhibited in vitro testicular steroidogenic responses in adult hypopysectomization rats.
Abstract: The direct effect of gonadotropin-releasing hormone (GnRH) and its agonist on testicular LH receptor and steroidogenesis was studied in hypophysectomized immature and adult rats. Hypophysectomized rats were treated daily with varying doses of GnRH or [des-Gly10,D-Leu6(N alpha Me)Leu7, Pro9-NHEt]GnRH(a potent agonist). Some animals were also treated concomitantly with FSH, PRL, GH and/or LH to prevent the hypophysectomy-induced loss of testicular LH receptor and steroidogenic capacity. At the end of 5 days of treatment, testicular LH/hCG receptor concentration was measured by a [125I]-hCG-binding assay and steroidogenic responsiveness was determinded by in vitro incubations. GnRH and the GnRH agonist reduced testicular LH receptor in control and FSH-treated hypophysectomized immature rats. As little as 0.5 microgram agonist/day induced a greater than 40% decrease in the LH receptor content, whereas GnRH was less potent, with 50 micrograms/day inducing about a 50% decrease. The inhibitory effect of GnRH was shown to be the result of decreases in the concentration of LH receptor rather than changes in the receptor affinity (Kd = 1.1 X 10(-10)M). GnRH did not interfere with the [125I]hCG receptor assay. Treatment with PRL, GH, and FSH, alone or in various combinations, increased the testicular LH receptor content. The stimulatory effect of these pituitary hormones was depressed by concomitant treatment with the GnRH agonist. Similar inhibitory effects of GnRH and the agonist on testicular LH receptor were demonstrated in adult hypophysectomized rats. In vitro studies demonstrated that treatment with the GnRH agonist in vivo inhibited both basal and hCG-stimulated androgen production in FSH-primed immature hypophysectomized rats. Associated with decreases in androgens (testosterone and androstenedione) and reduced androgens (dihydrotestosterone, androstanediol, and androsterone), there was marked suppression of 17 alpha-hydroxylated precursors and C-21 steroid intermediates in animals treated with the GnRH agonist, thus suggesting that the inhibitory effect of the GnRH agonist was associated with possible defects in 17 alpha-hydroxylase and side-chain cleavage enzymes. Likewise, treatment with the GnRH agonist inhibited in vitro testicular steroidogenic responses in adult hypopysectomized rats. These results demonstrate the extrapituitary inhibitory effect of GnRH on testicular LH receptor content and Leydig cell steroidogenesis in immature and adult hypophysectomized rats.
TL;DR: Three possible mechanisms by which E2 treatment could decrease plasma T wereinvestigated and no change was seen in prostate or seminal vesicle weight.
Abstract: The presence of an estrogen receptor in Leydig cell cytosol suggests that estrogen could have a direct action on Leydig cell function. We have studied the direct effects of estradiol (E2) on Leydig cell testosterone (T) biosynthesis using hypophysectomized rats treated daily for 4 days with 400 IU hCG (Pregnyl) and 1 IU human FSH (Pergonal), a model that eliminates the possibility of feedback effects of E2 on gonadotropin secretion. E2 was administered in sc silastic capsules. Rats having capsules that contained E2 were compared to rats having capsules that were empty. E2 treatment increased plasma E2 concentration from 380 ± 56 to 670 ± 64 pg/ml (mean ± se; P < 0.01) and decreased plasma T levels from 999 ± 167 to 461 ± 156 ng/100 ml (P < 0.01). These plasma steroid changes were associated with a decrease in testis weight from 1167 ± 170 to 870 ± 72 mg (P < 0.01). No change was seen in prostate or seminal vesicle weight. Three possible mechanisms by which E2 treatment could decrease plasma T were investi...
TL;DR: Dietary administration of dibutyl (DBP), di-iso-butyl (DIBP), or di-2-ethylhexyl phthalate (DEHP) induced severe atrophy of the testes, and testicular atrophy induced by PAEs may develop when high testosterone concentrations in the teste, and low zinc concentrations inThe testes and liver occur simultaneously.
TL;DR: In the male SH rat, ethanol metabolic rate appears to be limited by alcohol dehydrogenase activity and is modulated by testosterone.
Abstract: In young (4-week-old) male and female spontaneously hypertensive (SH) rats, ethanol metabolic rate in vivo and hepatic alcohol dehydrogenase activity in vitro are high and not different in the two sexes. In males, ethanol metabolic rate falls markedly between 4 and 10 weeks of age, which coincides with the time of development of sexual maturity in the rat. Alcohol dehydrogenase activity is also markedly diminished in the male SH rat and correlates well with the changes in ethanol metabolism. There is virtually no influence of age on ethanol metabolic rate and alcohol dehydrogenase activity in the female SH rat. Castration of male SH rats prevents the marked decrease in ethanol metabolic rate and alcohol dehydrogenase activity, whereas ovariectomy has no effect on these parameters in female SH rats. Chronic administration of testosterone to castrated male SH rats and to female SH rats decreases ethanol metabolic rate and alcohol dehydrogenase activity to values similar to those found in mature males. Chronic administration of oestradiol-17beta to male SH rats results in marked stimulation of ethanol metabolic rate and alcohol dehydrogenase activity to values similar to those found in female SH rats. Chronic administration of ethanol to male SH rats from 4 to 11 weeks of age prevents the marked age-dependent decreases in ethanol metabolic rate and alcohol dehydrogenase activity, but has virtually no effect in castrated rats. In the intoxicated chronically ethanol-fed male SH rats, serum testosterone concentrations are significantly depressed. In vitro, testosterone has no effect on hepatic alcohol dehydrogenase activity of young male and female SH rats. In conclusion, in the male SH rat, ethanol metabolic rate appears to be limited by alcohol dehydrogenase activity and is modulated by testosterone. Testosterone has an inhibitory effect and oestradiol has a testosterone-dependent stimulatory effect on alcohol dehydrogenase activity and ethanol metabolic rate in these animals.
TL;DR: Comparative measurements in spermatic vein plasma and peripheral plasma show that in general the testis has to secrete different amounts of the individual steroid to maintain the appropriate peripheral level, as well as for the diurnal rhythm, the age-related changes and for the increase after application of hCG.
Abstract: Oestrogens, testosterone, and 5 alpha-androstenone ('boar taint steroid') were determined in peripheral and spermatic vein blood plasma of boars. Oestrone was the predominant steroid in both the conjugated and the unconjugated fractions of total oestrogens. Concentrations of conjugated oestrogens in peripheral plasma generally are in the range of several nanograms/ml, which is similar to the range of 5 alpha-androstenone and testosterone. Unconjugated total oestrogens are in the lower nanogram-range. These concentrations, however, are still higher than those during the oestrus in sows. Stimulation with hCG led to increased concentrations of peripheral plasma oestrogens, demonstrating their testicular origin. Comparative measurements in spermatic vein plasma and peripheral plasma show that in general the testis has to secrete different amounts of the individual steroid to maintain the appropriate peripheral level. A highly correlated course of all the steroids measured was apparent. This was shown for the diurnal rhythm, the age-related changes and for the increase after application of hCG.
TL;DR: In this article, the authors used the male rhesus monkey as an experimental model for human reproductive function and found marked circannual variations in testicular exocrine and endocrine function.
Abstract: Testicular exocrine and endocrine function was monitored in adult male rhesus monkeys maintained for up to 4 years in a controlled environment isolated from seasonal changes in light, humidity and temperature and from female animals.
Marked circannual variations were found in both functions. Spermatogenesis and exocrine function were maximal in the autumn and winter months as indicated by histological studies and the measurement of testicular volume, frequency of spontaneous and provoked ejaculations and in sperm output. The serum level and metabolic clearance rate and production rate of testosterone were also maximal during this period as were the serum concentrations of dihydrotestosterone, cortisol and biologically active luteinizing hormone. By contrast the serum prolactin and dehydroepiandrosterone levels showed an inverse pattern, achieving their highest levels in spring, during the period of reduced testicular function.
Since such marked circannual variations in testicular and pituitary functions persist in monkeys isolated from external environmental influences, the existence of an inherent regulatory mechanism can be postulated. Such distinct variations in testicular function must be taken into consideration when using the male rhesus monkey as an experimental model for human reproductive function.
TL;DR: If alterations in the ability of granulosa cells to metabolize biologically active androgens to estrogens could constitute a physiologically significant mechanism for regulating the fate of developing follicles in the human ovary is investigated.
Abstract: The present study was undertaken to determine if alterations in the ability of granulosa cells to metabolize biologically active androgens to estrogens could constitute a physiologically significant mechanism for regulating the fate of developing follicles in the human ovary. This work was prompted by earlier studies with experimental animals which showed that estrogen stimulated growth and prevented atresia of preantral follicles, whereas androgen antagonized these effects and promoted atresia. Whole ovaries were obtained from seven young women undergoing unilateral ovariectomy during surgical correction of tubal infertility. The aromatase activities of granulosa cells collected from individual or pooled follicles were assessed by measuring the production of immunoreactive estrogen (17β-estradiol and estrone) during 3-h incubations of cells suspended in medium containing testosterone or androstenedione at a concentration of 10-7 M. Highest granulosa cell aromatase activities were associated with large, p...
TL;DR: Modulation of triglyceride-rich lipoprotein production by six steroids appears to be mediated to a significant extent by their effects on hepatic fatty acid utilization, and reflects in part the influence of sex steroids.
Abstract: The mechanism by which sex steroids influence very low density hepatic lipoprotein triglyceride production has not been fully elucidated In previous studies we showed that [(14)C]oleate utilization and incorporation into triglycerides were greater in hepatocyte suspensions from adult female rats than from males The sex differences were not related to activities of the enzymes of triglyceride biosynthesis, whereas fatty acid binding protein (FABP) concentration in liver cytosol was greater in females These findings suggested that sex differences in lipoprotein could reflect a sex steroid influence on the availability of fatty acids for hepatocellular triglyceride biosynthesis In the present studies, sex steroid effects on hepatocyte [(14)C]oleate utilization and FABP concentration were investigated directly Hepatocytes from immature (30-d-old) rats exhibited no sex differences in [(14)C]oleate utilization With maturation, total [(14)C]oleate utilization and triglyceride biosynthesis increased moderately in female cells and decreased markedly in male cells; the profound sex differences in adults were maximal by age 60 d Fatty acid oxidation was little affected Rats were castrated at age 30 d, and received estradiol, testosterone, or no hormone until age 60 d, when hepatocyte [(14)C]oleate utilization was studied Castration virtually eliminated maturational changes and blunted the sex differences in adults Estradiol or testosterone largely reproduced the appropriate adult pattern of [(14)C]oleate utilization regardless of the genotypic sex of the treated animal In immature females and males, total cytosolic FABP concentrations were similar In 60-d-old animals, there was a striking correlation among all groups (females, males, castrates, and hormone-treated) between mean cytosolic FABP concentration on the one hand, and mean total [(14)C]oleate utilization (r = 091) and incorporation into triglycerides (r = 094) on the other In 30-d-old animals rates of [(14)C]oleate utilization were greater, relative to FABP concentrations, than in 60-d-old animals The sex differences that characterize fatty acid utilization in adult rat hepatocytes are not present in cells from immature animals, and reflect in part the influence of sex steroids It remains to be determined whether the observed relationship of hepatic FABP concentration to [(14)C]oleate utilization in adult cells is causal or secondary to changes in cellular fatty acid uptake effected through another mechanism In either case, modulation of triglyceride-rich lipoprotein production by six steroids appears to be mediated to a significant extent by their effects on hepatic fatty acid utilization
TL;DR: The typical binding specificity of the androgen receptor and the regulatory effects of androgens on their own receptor support the possibility that some effect(s) of androgen upon skeletal muscles may be initiated directly at the cellular level through this receptor, a concept which is also in agreement with recently demonstrated in vitro effects ofandrogens on cultured myoblasts.
Abstract: Androgen binding has been studied in the quadriceps femoris of recently castrated adult and intact immature male and female rats using a variety of techniques for separating and measuring hormone-receptor complexes. [3H]Testosterone, [3H]androstanolone (or 5 alpha-dihydrotestosterone). [3H]methyltrienolone (a potent synthetic androgen), and [3H]estradiol bind to the androgen receptor. Affinities are identical for the first two hormones (Kd = approximately 70 pM) and lower for estradiol (Kd = approximately 0.2 nM), as determined by Scatchard plots of binding data. Competition experiments indicate that in addition to the nonradioactive steroids corresponding to the above-cited tritiated compounds, progesterone, cyproterone acetate (an antiandrogen), and spironolactone compete for [3H]androgen binding by the receptor, but diethylstilbestrol, moxestrol (a potent synthetic steroidal estrogen), and cortisol do not. 3 alpha- and 3 beta-androstanediols slightly inhibit testosterone binding. Therefore, striated muscle androgen receptor specificity is identical to that of all androgen receptors of target tissues which have been previously studied. Binding is abolished by pronase and heat treatment, and displays an approximate 7S sedimentation coefficient in low salt ultracentrifugation gradient analysis. Preliminary observations suggest hormone-induced receptor translocation into the nucleus. No evidence has been found for an independent estrogen receptor. In the course of the binding experiments, extensive metabolism of androstanoloe and testosterone was observed in muscle cytosol at 0-4 C, during the 2-h incubation period used for most binding studies. Metabolite formation can jeopardize the binding data, specifically altering the significance of competition experiments with relatively high concentrations of steroids approaching the Km of metabolizing enzymes. Therefore, most quantitative studies were performed in enzyme-free, receptor-containing cytosol preparations. In adult male rats castrated for 2 days, the concentration of receptor in the cytosol was of the order of 1 fmol/mg protein and corresponded to 72 fmol/mg tissue DNA (that is, 100 and 20 times less than that in corresponding prostatic cytosol, respectively). In the adult female rat 2 days after castration, the concentration of receptor in the cytosol was 0.34 fmol/mg protein. Treatment with testosterone pellets (20 mg for 15 days) increased androgen receptor concentration significantly. In spite of the relatively low concentration of androgen-binding sites, the typical binding specificity of the androgen receptor and the regulatory effects of androgens on their own receptor support the possibility that some effect(s) of androgens upon skeletal muscles may be initiated directly at the cellular level through this receptor, a concept which is also in agreement with recently demonstrated in vitro effects of androgens on cultured myoblasts.
TL;DR: It is concluded that the common occurrence of menstrual abnormalities in obesity results from abnormal secretion and binding of sex steroids, and the unaltered secretion of LH and FSH in the presence of such changes is evidence for a disorder of hypothalamic function.
Abstract: We have measured the plasma concentrations of sex steroids and sex hormone-binding globulin (SHBG) in twenty-three massively obese women and ten age-matched lean female volunteers. In the obese women increased plasma testosterone (obese 3.2 +/- 0.5 nmol/l controls 1.7 +/- 0.5 nmol/l, P less than 0.3) and androstenedione concentrations (obese 9.7 +/- 1.2 nmol/l, controls 4.4 +/- 0.6 nmol/l, P = less than 0.01) an increased ratio of oestrone:oestradiol (obese 2.4 +/- 0.4, controls 1.0 +/- 0.1, P = less than 0.1) and decreased SHBG levels (obese 30 +/- 4 nmol/l, controls 60 +/- 8 nmol/l, P = less than 0.001) were found. Obesity differed from the polycystic ovary syndrome (in which a similar pattern of changes of sex steroid concentrations and binding are seen) in that it was associated with normal increases in serum luteinizing hormone (LH) follicle stimulating hormone (FSH) levels in response to the administration of LHRH. We conclude that the common occurrence of menstrual abnormalities in obesity results from abnormal secretion and binding of sex steroids. In addition, the unaltered secretion of LH and FSH in the presence of such changes is evidence for a disorder of hypothalamic function.
TL;DR: The findings indicate that the acute elevations of intratesticular estrogen produced by treatment with hCG or GnRH are responsible for the steroidogenic lesion seen in gonadotropin-desensitized Leydig cells and suggest that locally produced estrogens contribute to the regulation of testicular LH receptors and 17,20 desmolase activity.
Abstract: Leydig cells isolated from the testes of rats treated with intravenous exogenous gonadotropin (hCG) or subcutaneous gonadotropin-releasing hormone (GnRH) show markedly decreased luteinizing hormone (LH) receptors and a partial block in testicular 17,20 desmolase activity. In contrast, Leydig cells from animals with equivalent degrees of LH receptor loss induced by subcutaneous hCG treatment show no change in 17,20 desmolase activity. These findings indicated that the acuteness of gonadotrophic stimulation, rather than the extent of LH receptor loss, was responsible for the steroidogenic lesion. A role of estradiol in the enzymatic block produced in vivo by acute elevation of circulating gonadotropin (intravenous hCG or GnRH-stimulated endogenous LH) was suggested by rapid elevations of testicular 17β-estradiol within 30 min after intravenous hCG, whereas more gradual increases in estradiol occurred 4-8 h after subcutaneous hCG. The inhibitory effect of endogenous estrogen on testicular steroidogenesis was confirmed by the ability of an estrogen antagonist (Tamoxifen) to prevent the reduction of testosterone responses caused by intravenous hCG and subcutaneous GnRH. In addition, Tamoxifen significantly increased the number of LH receptors in Leydig cells from both control and gonadotropin-desensitized animals. These findings indicate that the acute elevations of intratesticular estrogen produced by treatment with hCG or GnRH are responsible for the steroidogenic lesion seen in gonadotropin-desensitized Leydig cells. These results also suggest that locally produced estrogens contribute to the regulation of testicular LH receptors and 17,20 desmolase activity.
TL;DR: The prolonged response of plasma testosterone to a single injection of hCG should prompt a reevaluation of diagnostic and therapeutic regimens using this agent.
Abstract: The response of plasma testosterone to varying doses of hCG (0–6000 IU) given as a single im injection has been evaluated in normal men. After an initial rise at 2 h, the levels of testosterone demonstrated a secondary rise, reaching a peak 48 h after the im injection. The magnitude of the response varied directly with the dose of hCG used, and at the highest dose (6000 IU) testosterone levels were still elevated 6 days after administration. Plasma estradiol levels showed a dose-dependent rise, with peak levels being attained 24 h after hCG. The prolonged response of plasma testosterone to a single injection of hCG should prompt a reevaluation of diagnostic and therapeutic regimens using this agent.