Showing papers on "Testosterone published in 1991"

Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study.

Abstract: To evaluate the hypothesis that endocrine profiles change with aging independently of specific disease states, we examined the age trends of 17 major sex hormones, metabolites, and related serum proteins in 2 large groups of adult males drawn from the Massachusetts Male Aging Study, a population-based cross-sectional survey of men aged 39-70 yr conducted in 1986-89. Group 1 consisted of 415 men who were free of obesity, alcoholism, all prescription medication, prostate problems, and chronic illness (cancer, coronary heart disease, hypertension, diabetes, and ulcer). Group 2 consisted of 1294 men who reported 1 or more of the above conditions. Each age trend was satisfactorily described by a constant percent change per yr between ages 39-70 yr. Free testosterone declined by 1.2%/yr, and albumin-bound testosterone by 1.0%/yr. Sex hormone-binding globulin (SHBG), the major serum carrier of testosterone, increased by 1.2%/yr, with the net effect that total serum testosterone declined more slowly (0.4%/yr) than the free or albumin-bound pools alone. Among the major androgens and metabolites, androstane-3 alpha,17 beta-diol (androstanediol; 0.8%/yr) and androstanediol glucuronide (0.6%/yr) declined less rapidly than free testosterone, while 5 alpha-dihydrotestosterone remained essentially constant between ages 39-70 yr. Androstenedione declined at 1.3%/yr, a rate comparable to that of free testosterone, while the adrenal androgen dehydroepiandrosterone (3.1%/yr) and its sulfate (2.2%/yr) declined 2-3 times more rapidly. The levels of testosterone, SHBG, and several androgen metabolites followed a parallel course in groups 1 and 2, remaining consistently 10-15% lower in group 2 across the age range of the study. Subgroup analyses suggested that obese subjects might be responsible for much of the group difference in androgen level. Serum concentrations of estrogens and cortisol did not change significantly with age or differ between groups. Of the pituitary gonadotropins, FSH increased at 1.9%/yr, LH increased at 1.3%/yr, and PRL declined at 0.4%/yr, with no significant difference between groups 1 and 2.(ABSTRACT TRUNCATED AT 400 WORDS)

Hormonal induction of all stages of spermatogenesis in vitro in the male Japanese eel (Anguilla japonica)

Abstract: The importance of gonadotropins and androgens for spermatogenesis is generally accepted in vertebrates, but the role played by specific hormones has not been clarified. Under cultivation conditions, male Japanese eels (Anguilla japonica) have immature testes containing only premitotic spermatogonia, type A and early-type B spermatogonia. In the present study, a recently developed organ-culture system for eel testes was used to determine in vitro effects of various steroid hormones on spermatogenesis. After 9 days of culture in serum-free, chemically defined medium containing 11-ketotestosterone (10 ng/ml), a major androgen in male eels, type A and early-type B spermatogonia began mitosis, producing late-type B spermatogonia. After 18 days, zygotene spermatocytes with synaptonemal complexes appeared, indicating that meiosis had already started by this time. In testis fragments cultured for 21 days, round spermatids and spermatozoa were observed with spermatogenic cells at all stages of development. Addition of 11-ketotestosterone to the culture medium also caused a marked cytological activation of Sertoli cells. No other steroid hormones tested had such stimulatory effects. These results, together with our earlier observations, suggest the following sequence for the hormonal induction of spermatogenesis in eel testes; gonadotropin stimulates the Leydig cells to produce 11-ketotestosterone, which, in turn, activates the Sertoli cells leading to the completion of spermatogenesis. This is, thus, an example of an animal system in which all stages of spermatogenesis have been induced by hormonal manipulation in vitro.

Longitudinal assessment of changes in reproductive hormones during normal pregnancy.

Abstract: The concentrations of hormones measured in serum from maternal blood change dramatically during pregnancy. While the relative contributions of sex steroids shift from maternal ovaries and adrenals to the fetoplacental unit, other maternal tissues such as pituitary and liver respond to increasing concentrations of estrogen and secrete increasing amounts of prolactin and sex-hormone-binding globulin. To determine longitudinal changes in circulating maternal hormones, we collected blood from 60 women on three occasions during their pregnancies. We observed a 1.7-fold increase in testosterone concentration in serum; concentrations of sex-hormone-binding globulin in serum rose 5.6-fold. The major increase (6.8-fold) in estradiol in serum occurred within the first 16 weeks, followed by a further 4.8-fold increase by term. Mean concentrations of progesterone, 17-hydroxyprogesterone, and androstenedione in serum increased 11.9-, 3-, and 1.3-fold, respectively, whereas concentrations of dehydroepiandrosterone sulfate (DHEAS) fell by 50%. Mean serum prolactin concentrations increased 3.8-fold during the first trimester and by a similar amount during the final 24 weeks of pregnancy. We used these data, obtained from a cohort of women with uncomplicated pregnancies, to construct reference intervals for hormones in maternal serum.

Effect of testosterone on abdominal adipose tissue in men.

Abstract: Recent studies in men have shown that abdominal fat increases with age and decreasing testosterone concentrations Furthermore, in cell culture, testosterone expresses an increased lipolytic potential and depresses lipoprotein lipase activity (LPL) in adipose cells These metabolic characteristics are found in abdominal adipose tissue in young men In order to see whether abdominal fat masses in moderately obese middle-aged men might be diminished by testosterone, this hormone was given either as a single injection (500 mg) or in moderate doses (40 mg X 4) for 6 weeks in an oral preparation, bypassing the liver When measured 1 week after the single dose, abdominal LPL tended to decrease After 6 weeks a dramatic decrease of abdominal LPL was found, as well as an increase in the lipolytic responsiveness to norepinephrine, both changes confined solely to the abdominal, and not femoral adipose tissue regions The waist/hip circumference decreased in 9 out of the 11 examined men No untoward effects were seen in behavioural variables, blood pressure, triglyceride or cholesterol values, and liver function tests These preliminary results suggest that administration of testosterone in moderate doses to middle-aged men lead to adaptations of the metabolism of adipose tissue expected to be followed by a diminution of this mass

Regulation of cytochrome P450 aromatase messenger ribonucleic acid and activity by steroids and gonadotropins in rat granulosa cells.

Abstract: Estradiol (E) biosynthesis by the cytochrome P450 aromatase (P450arom) enzyme system increases as preovulatory follicles develop and is subsequently reduced by the ovulatory LH surge. To determine the specific effects of gonadotropins and steroids on expression of P450arom in rat granulosa cells, steady state levels of messenger (m) RNA were examined in vivo and in vitro, with the latter also being related to aromatase enzyme activity and cAMP production. P450arom mRNA and activity were induced in granulosa cells by FSH alone in a dose-, time-, and stage-dependent manner. E enhanced the effects of FSH in vivo and in vitro. The synergistic effect of E with FSH (50 ng/ml) was observed in the absence/presence of serum and was mimicked by a similar concentration (20 nM) of testosterone, dihydrotestosterone, or dexamethasone. In contrast, ovulatory doses of LH (500 ng/ml) or forskolin (10 microM) but not concentrations of progesterone reached in preovulatory follicles (100-1000 nM) acted on differentiated (FSH + E) granulosa cells to cause a rapid loss of P450arom mRNA. Whereas cycloheximide prevented the LH/cAMP-mediated decrease in P450arom mRNA in the differentiated cells, enzyme activity remained unaltered during the same 6-h period. Thus, expression of aromatase mRNA in rat granulosa cells is induced primarily by low FSH/cAMP, enhanced by physiological doses of several steroids (except progesterone), and, once induced, can be rapidly inhibited by elevated gonadotropin/cAMP via a pathway requiring protein synthesis.

Regulation of estrogen receptor messenger ribonucleic acid in rat hypothalamus by sex steroid hormones

Abstract: Sex steroid hormone receptors are thought to mediate the actions of their respective hormones by functioning as ligand-activated nuclear transcription factors that alter the expression of specific sets of hormone-responsive genes. Particularly high densities of estrogen receptor (ER)-containing neurons are located in the arcuate nucleus (ARH) and ventrolateral part of the ventromedial nucleus (VMHvl) of the hypothalamus, and these cell groups are thought to play key roles in the neuroendocrine control of reproductive function. Thus, hormonal regulation of ER gene expression in ARH and VMHvl neurons represents a direct mechanism by which circulating sex steroids could affect the responsiveness of these neurons to hormonal activation. We used in situ hybridization histochemistry to evaluate the influence of estradiol and testosterone on levels of ER mRNA within the ARH and VMHvl of adult male and female rats. In female rats, estradiol treatment reduced levels of ER mRNA in the ARH and VMHvl within 24 h relative to levels in both ovariectomized control animals and intact estrous females. Comparable results were obtained in male rats, except that testosterone did not significantly attenuate ER mRNA hybridization in the VMHvl until after 3 days of hormone treatment, and only a minor decrease was noted in the ARH, which was not statistically significant. In both male and female animals, the overall density of labeling found over individual cells in emulsion-dipped autoradiograms was consistently lower in hormone-treated animals compared with that over cells in gonadectomized controls, suggesting that the observed decreases in ER mRNA hybridization measured over the ARH and VMHvl are due to changes in cellular levels of ER mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Associations of Body Mass and Fat Distribution with Sex Hormone Concentrations in Postmenopausal Women

Abstract: The associations of body mass and body fat distribution, as measured by waist-to-hip circumference ratio, with serum concentrations of sex hormones and sex hormone binding globulin were examined in 88 postmenopausal women. Body mass index (BMI) was significantly and negatively associated with sex hormone binding globulin (SHBG) (r = -0.41), luteinizing hormone (LH) (r = -0.40) and follicle stimulating hormone (FSH) (r = -0.38) and was also significantly positively associated with both total and free oestradiol (r = 0.40 and 0.45, respectively). Waist-to-hip circumference ratio was significantly negatively correlated with SHBG (r = -0.53), LH (r = -0.35), and FSH (r = -0.35). After adjustment for BMI and other related factors, waist-to-hip circumference ratio was significantly and negatively associated with SHBG, LH, and FSH, and demonstrated a significant curvilinear relationship with free testosterone. These results suggest that in postmenopausal women, abdominal adiposity is associated with a relatively more androgenic sex hormone profile.

Normative Data for Adrenal Steroidogenesis in a Healthy Pediatric Population: Age- and Sex-Related Changes after Adrenocorticotropin Stimulation

Abstract: The normal response to a single 0.25-mg dose of ACTH-(1-24) is not well established in infancy or childhood. We report the adrenal steroidogenic responses of 17-hydroxypregnenolone (17OH Preg), 17-hydroxyprogesterone (17OH Prog), 11-deoxycortisol, cortisol, deoxycorticosterone, dehydroepiandrosterone (DHEA), DHEA sulfate, androstenedione (A'dione), and testosterone in 102 healthy children who were divided into 5 groups: group 1 (less than 1 yr old; n = 22), group 2 (1-5 yr old; n = 22), group 3 (6-12 yr old; n = 15), group 4 (early-midpuberty; n = 21), and group 5 (late puberty; n = 22). Baseline and stimulated levels of 17OH Preg were significantly higher in group 1 infants than in group 2 children (P less than 0.01). Baseline levels of 17OH Prog increased in late puberty (P less than 0.01). Baseline and stimulated levels of DHEA rose in late puberty (group 5 vs. group 3, P less than 0.01). DHEA levels in late pubertal females were higher than those in their male counterparts (P less than 0.01). DHEA sulfate levels did not change after ACTH administration in any age group. Baseline and stimulated levels of A'dione rose significantly before the onset of puberty in female children (group 2 vs. group 3, P less than 0.01). The calculated ratio of 17OH Preg/17OH Prog in group 1 was significantly higher than that in other groups of children (P less than 0.01). The calculated, baseline DHEA/A'dione ratio was higher in group 1 than in older children (P less than 0.01). Stimulated ratios were higher in late pubertal females than in males (P less than 0.01). In both sexes baseline and stimulated ratios of 17OH Prog/deoxycorticosterone increased in puberty, such that late pubertal children had higher levels than prepubertal children (P less than 0.01). These data confirm the need for interpretation ACTH stimulation test data to be based upon age- and sex-specific norms.

Androgen replacement therapy in male patients with rheumatoid arthritis.

Abstract: A hypogonadic condition characterized by low serum testosterone levels has been identified in male patients with rheumatoid arthritis (RA). Seven men with active RA were treated daily for 6 months with oral testosterone undecanoate plus a nonsteroidal antiinflammatory drug in an attempt to evaluate the immunologic response, the overall clinical response, and the sex hormone response to such replacement therapy. At the end of the 6 months, there was a significant increase in serum testosterone levels (P less than 0.05), an increase in the number of CD8+ T cells, and a decrease in the CD4+:CD8+ T cell ratio. The IgM rheumatoid factor concentration decreased significantly (P less than 0.05). There was a concurrent significant reduction in the number of affected joints (P less than 0.05) and in the daily intake of nonsteroidal antiinflammatory drugs (P less than 0.01). The well-known immunosuppressive action of androgens probably contributed to our findings in these RA patients.

Early hypothyroidism in rats causes increased adult testis and reproductive organ size but does not change testosterone levels.

Abstract: The role of thyroid hormones in the testis is unclear, although recent evidence indicates they may be important for testicular development. Here we describe a novel method for increasing adult testicular size in the rat by induction of transient hypothyroidism during neonatal life. Rats were treated with a reversible goitrogen, 6-propyl-2-thiouracil from birth to day 25 when treatment was stopped, allowing return to a euthyroid state. At days 90, 135, 160, and 180, wt and DNA content of the testis, epididymis, ventral prostate, seminal vesicle, and those of some nonreproductive organs were determined, as well as serum levels of testosterone (T) and thyroid hormones. Despite decreased body wts in 90-day and older 6-propyl-2-thiouracil-treated rats, testis wt was increased by 40% and 60% at 90 and 135 days, respectively; maximal increase (80%) occurred at 160 days. These wt increases were accompanied by proportional changes in DNA content. Significant enlargements were also seen in other reproductive organs, but they occurred after a time lag and were smaller in magnitude. Interestingly, serum T levels showed no increase at any age. Weight and DNA content of nonreproductive organs, like body wts, were less than controls at all ages but thyroid hormone levels were normal. Thus, transient hypothyroidism in neonatal rats is associated with lasting enlargements in the ultimate size of testis and other reproductive organs in the adult. These changes are not related to excess T levels. The results indicate early critical influences of thyroid hormones on growth and development of the reproductive system and suggest an experimental model for inducing lasting enlargements in testis and reproductive organs. The model may also be useful for studying regulation of reproductive growth and final size.

Testosterone increases lipolysis and the number of beta-adrenoceptors in male rat adipocytes.

Abstract: The influence of androgen status on the regulation of lipolysis and number of beta-adrenoceptors in isolated adipocytes was studied in male rats. Castration resulted in decreased catecholamine-induced as well as forskolin-induced lipolysis. beta-adrenoceptor number, examined by a whole cell cyanopindolol binding assay, was also diminished to a similar extent. Testosterone treatment of castrated rats normalized lipolysis as well as beta-adrenoceptor number. These results demonstrate that testosterone stimulates catecholamine-induced lipolysis in vivo by increasing the number of beta-adrenoceptors as well as the activity of adenylate cyclase, confirming previous in vitro studies performed in adipose precursor cells.

Clinical and Biochemical Parameters of Androgen Action in Normal Healthy Caucasian Versus Chinese Subjects

Abstract: Stimulation of androgen-sensitive hair follicles is mediated by dihydrotestosterone (DHT), which is formed in these tissues by 5α-reduction of testosterone. A possible mechanism for increased body hair in some human populations might, therefore, be an increase in 5α-reductase activity, resulting in elevated tissue levels of DHT. If present, this finding could have other important clinical implications, since the 5α-reductase enzyme is pivotal in the pathophysiology of prostatic disease. To explore differences in clinical and biochemical parameters of androgen action, we conducted a study of 184 Caucasian and Chinese subjects in whom we evaluated chest hair density and serum levels of androgen precursors and 5α-reduced androgen metabolites. Differences in chest hair density were most notable in the men, in whom comparative mean chest hair scores (using a scale of 0-4) were 3.0 vs. 0.8 (P < 0.0001), Caucasian vs. Chinese. Levels of 5α-reduced androgen products were also strikingly higher in the Cau...

An animal model for the effects of estradiol on dopamine-mediated behavior: implications for sex differences in schizophrenia.

Abstract: Schizophrenic women have been consistently found to have a later age of onset and a less severe clinical course of illness as compared with schizophrenic men. Because these differences are not explained by diagnostic artifacts or sociocultural factors, we tested the hypothesis that they are determined by the influence of the gonadal hormones testosterone and estradiol on dopaminergic (DA) neurotransmission. We used animal models in which the effects of the hormones on behavioral changes induced by the DA antagonist haloperidol (catalepsy) and by the DA agonist apomorphine (oral stereotypies, grooming and sitting behavior) were investigated in neonatal and in adult treated rats. No consistent effects of testosterone were observed. Estradiol significantly reduced the behavioral changes induced by both haloperidol and apomorphine, and this effect was more pronounced in neonatally treated animals. These results suggest a downward regulation of DA neurotransmission by estradiol, which is supported by the results of 3H-sulpiride binding determinations in brain homogenates from the same animals: estradiol caused a 2.8-fold reduction of DA receptor affinity to sulpiride. Our findings suggest that estradiol might act as a protective modulator in schizophrenia by enhancing the vulnerability threshold for psychosis through the downward regulation of DA neurotransmission. Such mechanism could explain, at least in part, the later onset and the more favorable course of schizophrenia in female patients.

Influence of the paraventricular nucleus of the hypothalamus in the alteration of neuroendocrine functions induced by intermittent footshock or interleukin.

Abstract: The documented ability of physical stress and cytokines to increase the secretion of corticotropin-re lea sing factor CRF by the paraventricular nucleus of the hypothalamus (PVN), coupled with our earlier demonstration that CRP acts within the brain to interfere with reproductive functions, led us to investigate the effect of lesions of the PVN on LH, testosterone, ACTH, and corticosterone (CORT) secretion. Bilateral lesions of the PVN were done electrolytically, and 2 weeks later a series of acute and chronic experiments were performed in intact or castrated male rats bearing indwelling jugular and/or intracerehroventricularcannulas. The first study involved a single 2-h exposure of intact male rats to footshocks (2 mA, 2-sec duration, 4 per min). Although PVN lesions did not measurably alter the ability of intermittent footshock to lower plasma testosterone levels, this treatment attenuated the rise in plasma ACTH and CORT. In a second study, which was done in castrated rata, shocks were delivered 2 h d...

Reproductive endocrine considerations and hormonal therapy for men with epilepsy.

Abstract: Androgen deficiency is unusually common among men with epilepsy. It may contribute to reproductive and sexual dysfunction and possibly exacerbate seizure frequency. The most important androgen is testosterone. it exists in the serum in a free form or bound to albumin or sex hormone-binding globulin (SHBG). Free testosterone levels have correlated significantly with measures of potency and sexual interest. The possibility that measures of non-SHBG-bound testosterone may provide a more sensitive assessment of biologically and perhaps clinically significant androgen levels is raised for consideration. Androgen deficiency may result from increased catabolism and binding induced by antiepileptic drugs (AEDs). It is a feature of the reproductive endocrine disorders that are often associated with epilepsy: hypogonadotropic hypogonadism, hypergonadotropic hypogonadism, and functional hyperprolactinemia. It may be a consequence of medication-induced elevations in serum estradiol. Estradiol exerts a potent inhibitory influence on luteinizing hormone secretion and may contribute to premature aging of the reproductive system, both at the level of the testes and the hypothalamus. Testosterone therapy may moderately benefit reproductive and sexual function. Despite its antiseizure effects in animal experiments, however, it has not been reported to improve seizures clinically. One possible explanation is that AEDs that induce enzyme synthesis may enhance the conversion of testosterone to estradiol by aromatase. This possibility is supported by the improved seizure control achieved with the adjunctive use of the aromatase inhibitor testolactone or the antiestrogen clomiphene.

High-Affinity Androgen Binding and Androgenic Regulation of α1(I)-Procollagen and Transforming Growth Factor-β Steady State Messenger Ribonucleic Acid Levels in Human Osteoblast-Like Osteosarcoma Cells*

Abstract: Clinical observations have demonstrated a positive effect of estrogens and androgens on the maintenance of structural bone integrity. This study examines the direct effects of androgenic hormones on the osteoblast-like human osteosarcoma cell line, HOS TE85. Employing radiolabeled dihydrotestosterone (DHT), 2800 saturable, high-affinity (dissociation constant = 0.66 nM) androgen binding sites were detected per HOS TE85 cell. Androgen binding was specific in that DHT and testosterone (T) displayed significantly greater competition than the progestins, progesterone and medroxyprogesterone. The expression of androgen receptors in HOS TE85 cells was further substantiated by Northern analysis. A human androgen receptor complementary DNA probe revealed a 9.5 kilobase transcript which corresponds to the predominant human androgen receptor transcript detected in human male reproductive tissues. Androgens were also found to elicit biological responses in HOS TE85 cells. Physiological concentrations of DHT and T de...

Effects of testosterone on a selected neuronal population within the preoptic sexually dimorphic nucleus of the japanese quail

Abstract: The effects of testosterone on the volume and cytoarchitecture of the sexually dimorphic nucleus of the preoptic area (POM) were investigated in male and female Japanese quail. It was confirmed that castration decreases the POM volume in males and that, in gonadectomized birds of both sexes, testosterone increases this volume to values similar to those observed in intact sexually mature males. This suggests that the sex difference in POM volume results from a differential activation by T so that this brain morphological characteristic is not truly differentiated in the organizational sense. This conclusion was extended here by demonstrating that males exposed to a photoperiod simulating long days and that are known to have high plasma levels of testosterone have a larger POM than short-day males that have inactive testes. Detailed morphometric studies of POM neurons revealed a structural heterogeneity within the nucleus. A population of large neurons (cross-sectional area larger than 70-80 microns2) was well represented in the dorsolateral but was almost absent in the medial part of POM. This lateral population of neurons was sensitive to variations of testosterone levels in males but not in females. The cross-sectional area, diameter, and perimeter of the dorsolateral neurons were significantly increased in males exposed to high testosterone levels (intact birds exposed to long days or castrated birds treated with the steroid). These changes were not observed in the medial part of the nucleus. Interestingly, the size of the dorsolateral neurons was not affected by testosterone treatments in females. These results suggest that the swelling of neurons in the lateral POM of males might be responsible for the increase in total volume of the nucleus, which is observed in physiological situations associated with a high testosteronemia. In addition, the sensitivity to testosterone of the dorsolateral neurons in the POM appears to be sexually differentiated. This differential response to testosterone might represent a truly dimorphic feature in the organizational sense and additional studies manipulating the early steroid environment should be performed to test this possibility.

Social suppression of reproduction in male naked mole-rats, Heterocephalus glaber.

Abstract: To investigate possible anatomical and endocrine differences between breeding and non-breeding male naked mole-rats, 113 animals from 24 captive and 4 wild colonies were studied. While breeding males had larger reproductive tract masses compared to non-breeders relative to body mass (P less than 0.01), spermatogenesis was active in all of the non-breeding males examined histologically (n = 9) and spermatozoa were present in the epididymides. Compared with non-breeders, breeding males had significantly higher urinary testosterone concentrations (mean +/- s.e.m.: 23.8 +/- 2.3 vs 5.2 +/- 1.4 ng/mg Cr respectively; P less than 0.001), and plasma LH (10.7 +/- 1.7 vs 5.0 +/- 0.8 mi.u./ml respectively; P less than 0.01). Single doses of 0.1, 0.5 or 1.0 microgram GnRH produced a significant rise in plasma LH concentrations 20 min after s.c. injection in breeding and non-breeding males at all doses (P less than 0.001). However, there were differences in the magnitude of the LH response following administration of GnRH between breeding and non-breeding males, with non-breeding males showing a dose-response and having lower plasma LH concentrations 20 min after a single injection of 0.1 or 0.5 microgram (P less than 0.05), but not 1.0 microgram, GnRH. This apparent lack of pituitary sensitivity of non-breeding males to single doses of exogenous GnRH was reversed by 4 consecutive injections of 0.5 microgram GnRH at hourly intervals, suggesting that the reduced sensitivity may be the result of insufficient priming of the pituitary by endogenous GnRH. These results indicate that, despite the fact that non-breeding males were apparently producing mature gametes, clear endocrine deficiencies existed in male naked mole-rats.

Sex Differences in Androgen Receptors and Aromatase Activity in Microdissected Regions of the Rat Brain

Abstract: Males are generally more responsive than females to the behavioral and neuroendocrine actions of androgens. The present experiments were performed to determine whether these differences may result from sex differences in the number of androgen receptors (AR) in specific brain areas. For this reason, AR binding was compared in both cytosol (ARc) and cell nuclear KC1 extracts (ARn) from microdissected brain regions of gonadectomized male and female rats treated with doses of testosterone (T) that produced equivalent physiological circulating androgen levels. In addition, microsomal aromatase activity was measured as a biochemical index of tissue responsiveness to T, since estrogen formation in certain brain areas is regulated by androgen. One week after exogenous T administration, males exhibited significantly higher levels of ARn than females in the bed nucleus of the stria terminalis, periventricular preoptic area, and ventromedial nucleus. Males also had significantly higher aromatase levels in these sam...

Endogenous sex hormones, high density lipoprotein cholesterol, and other lipoprotein fractions in men.

Abstract: At least some of the large preponderance for coronary heart disease in men has been attributed to differences in lipid and lipoprotein levels; notably, high density lipoprotein cholesterol (HDL-C), a protective factor, is higher in women. The sex differences in lipid levels have been postulated to be related to differences in sex hormones. In a southern California cohort of 391 men aged 30-79 years, HDL-C levels were positively correlated and very low density lipoprotein cholesterol (VLDL-C) levels were inversely correlated with testosterone levels independently of age, body mass index, physical exercise, smoking, and alcohol intake. Mean HDL-C levels were 12% higher and VLDL-C levels were 40% lower in the highest compared with the lowest quartile of testosterone level. Low density lipoprotein cholesterol levels were positively related to estrone, estradiol, and androstenedione levels. It is premature to attribute the sex differential in lipid cardiovascular risk profiles to higher levels of testosterone per se in men, since testosterone levels are favorably associated with cardiovascular risk while estrogen levels have the converse relation in men. The differing effects and interactions of specific endogenous sex hormones in men and women require further elucidation.

Sex difference in estradiol regulation of progestin receptor mRNA in rat mediobasal hypothalamus as demonstrated by in situ hybridization.

Abstract: Previous studies have shown that estrogen increases the level of progestin receptors (PR) to a greater extent in female than in male rat hypothalamus. In order to determine if sex-specific regulation of the PR protein might be attributable to estrogenic effects on the PR message, in situ hybridization was used to assess sex differences in levels of estrogen-inducible PR mRNA in specific brain nuclei. Here, we report a sexually differentiated pattern of estrogen-regulated PR gene expression. In female hypothalamus, estrogen administered to gonadectomized rats induced a 3.6- and a 3.3-fold increase in PR mRNA in the ventrolateral aspect of the ventromedial nucleus and arcuate nucleus, respectively, but failed to alter the level of PR mRNA in the same neuronal groups of the male. Hormone treatment did not affect the levels of PR mRNA in the dorsomedial or medial amygdaloid nuclei of either sex. These results lead towards a molecular explanation of sex differences in female reproductive behavior by revealing an estrogen-dependent up-regulation of the message for PR, a transcription factor, in a region- and sex-specific fashion.

Testosterone differentially regulates the regenerative properties of injured hamster facial motoneurons.

Abstract: We have previously demonstrated that systemic administration of testosterone accelerates functional recovery, as measured behaviorally, from facial paralysis induced by facial nerve crush axotomy in gonadectomized adult male hamsters. In this investigation, the hypothesis that testosterone enhances return of motor function by increasing the rate of axonal regeneration following injury was tested using fast axonal transport of radioactively labeled proteins to assess facial nerve regeneration. Adult castrated and intact males, and intact females, were subjected to right facial nerve crush axotomy at the stylomastoid foramen. One-half of the axotomized animals in each group received subcutaneous implants of testosterone, with the remainder of the animals sham implanted. Systemic administration of testosterone resulted in a 26-30% increase in the rate of regeneration of the fastest growing population of axons in the male experimental groups, regardless of whether the animal was castrated or not. This rate increase is similar to that observed in the conditioning lesion paradigm utilized by others. In the females, testosterone had a significant, but less pronounced, effect on the rate of axonal regeneration, which may be due in part to inherent gender-related differences in regenerative properties of facial motoneurons. A surprising finding of this study was that no shortening of the delay of sprout formation by testosterone was observed across the various experimental groups. These data suggest that the mechanism by which gonadal steroids act in the injured nervous system is partly through the differential regulation of the regenerative properties of the injured cell, presumably via hormone receptor-mediated action at the level of the neuronal genome.

Feed-forward control of prostate growth: Dihydrotestosterone induces expression of its own biosynthetic enzyme, steroid 5α-reductase

Abstract: Dihydrotestosterone, the primary mediator of prostate growth, is synthesized in target tissues from the circulating androgen testosterone through the action of steroid 5 alpha-reductase (EC 1.3.99.5). The expression of 5 alpha-reductase and the level of 5 alpha-reductase messenger RNA in rat ventral prostate are regulated by androgens. To determine whether this control is mediated by dihydrotestosterone or testosterone, we investigated the effect of finasteride, a potent inhibitor of steroid 5 alpha-reductase, on the expression of 5 alpha-reductase in the prostate. The administration of finasteride to intact rats for 7 days caused a 55% decrease in prostate weight and an 87% decrease in 5 alpha-reductase enzyme activity. Furthermore, the restoration of prostate growth after castration and the enhancement in 5 alpha-reductase enzyme activity and 5 alpha-reductase messenger RNA level by testosterone administration were blocked by finasteride, whereas the inhibitor had no effect on dihydrotestosterone-mediated increases in 5 alpha-reductase activity or messenger RNA level. These findings indicate that dihydrotestosterone itself controls prostate growth and 5 alpha-reductase activity. They further suggest that prostate growth is controlled by a feed-forward mechanism by which formation of trace amounts of dihydrotestosterone induces 5 alpha-reductase, thereby increasing dihydrotestosterone synthesis and triggering a positive developmental cascade.

Maturation of hypothalamic-pituitary-gonadal function in normal human fetuses: Circulating levels of gonadotropins, their common α-subunit and free testosterone, and discrepancy between immunological and biological activities of circulating follicle-stimulating hormone

Abstract: The recent availability of both cordocentesis, a low risk and effective technique for fetal blood sampling, and ultrasensitive/highly specific two-site immunofluorometric assays (IFMA) for pituitary and chorionic glycoprotein hormone (I-LH, I-FSH, and I-CG) measurement prompted us to study the maturation of hypothalamic-pituitary-gonadal function in 114 normal human fetuses (49 females and 65 males) from 17-40 weeks gestation. The subjects were selected from 216 consecutive cordocenteses carried out for rapid karyotyping and diagnosis of fetal infection or hematological disorders. In addition, FSH bioactivity (B-FSH) was measured by rat Sertoli cell aromatase induction assay, glycoprotein hormone alpha-subunit (alpha-SU) by RIA, and circulating free testosterone (fT) by direct analog technique. No significant cross-reactions were recorded in the different measurement methods. In particular, alpha-SU did not interfere in any IFMA, and CG cross-reactivity in LH IFMA was 0.5%. Circulating I-LH, I-FSH, and B-FSH levels at 17-24 weeks gestation were significantly higher in female than in male fetuses (I-LH, 48 +/- 4 vs. 6.3 +/- 0.7 U/L; I-FSH, 35 +/- 2 vs. 0.7 +/- 0.1 U/L; B-FSH, 131 +/- 17 vs. 43.4 +/- 5.4 U/L). During the last weeks of gestation, a significant decrease in I-LH and I-FSH levels was seen in both female and male fetuses (I-LH, 0.24 +/- 0.05 and 1.0 +/- 0.3 U/L; I-FSH, 0.45 +/- 0.1 and 0.5 +/- 0.1 U/L), while serum B-FSH remained elevated, but the previously recorded difference between sexes disappeared (54.3 +/- 7.2 and 58.7 +/- 7.3 U/L). Circulating I-CG and alpha-SU levels at midgestation were elevated in both female and male fetuses (I-CG, 117 +/- 29 and 191 +/- 44 U/L; alpha-SU, 143 +/- 16 and 105 +/- 9 micrograms/L, respectively) and decreased thereafter (I-CG, 42 +/- 9 and 26 +/- 6 U/L; alpha-SU, 60 +/- 15 and 37 +/- 6 micrograms/L). Serum fT levels at midgestation were significantly lower in females than in males (4.3 +/- 0.9 vs. 10.0 +/- 0.8 pmol/L) and increased until term, when the difference between sexes disappeared (16.2 +/- 1.8 vs. 17.6 +/- 1.6 pmol/L).(ABSTRACT TRUNCATED AT 400 WORDS)