Showing papers on "Testosterone published in 1994"

Induction of calcium-dependent nitric oxide synthases by sex hormones

Abstract: We have examined the effects of pregnancy and sex hormones on calcium-dependent and calcium-independent nitric oxide synthases (NOSs) in the guinea pig. Pregnancy (near term) caused a > 4-fold increase in the activity of calcium-dependent NOS in the uterine artery and at least a doubling in the heart, kidney, skeletal muscle, esophagus, and cerebellum. The increase in NOS activity in the cerebellum during pregnancy was inhibited by the estrogen-receptor antagonist tamoxifen. Treatment with estradiol (but not progesterone) also increased calcium-dependent NOS activity in the tissues examined from both females and males. Testosterone increased calcium-dependent NOS only in the cerebellum. No significant change in calcium-independent NOS activity was observed either during pregnancy or after the administration of any sex hormone. Both pregnancy and estradiol treatment increased the amount of mRNAs for NOS isozymes eNOS and nNOS in skeletal muscle, suggesting that the increases in NOS activity result from enzyme induction. Thus both eNOS and nNOS are subject to regulation by estrogen, an action that could explain some of the changes that occur during pregnancy and some gender differences in physiology and pathophysiology.

Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age

Abstract: Aging in humans is accompanied by a progressive decline in the secretion of the adrenal androgens dehydroepiandrosterone (DHEA) and DHEA sulfate (DS), paralleling that of the GH-insulin-like growth factor-I (GH-IGF-I) axis. Although the functional relationship of the decline of the GH-IGF-I system and catabolism is recognized, the biological role of DHEA in human aging remains undefined. To test the hypothesis that the decline in DHEA may contribute to the shift from anabolism to catabolism associated with aging, we studied the effect of a replacement dose of DHEA in 13 men and 17 women, 40-70 yr of age. A randomized placebo-controlled cross-over trial of nightly oral DHEA administration (50 mg) of 6-month duration was conducted. During each treatment period, concentrations of androgens, lipids, apolipoproteins, IGF-I, IGF-binding protein-1 (IGFBP-1), IGFBP-3, insulin sensitivity, percent body fat, libido, and sense of well-being were measured. A subgroup of men (n = 8) and women (n = 5) underwent 24-h sampling at 20-min intervals for GH determinations. DHEA and DS serum levels were restored to those found in young adults within 2 weeks of DHEA replacement and were sustained throughout the 3 months of the study. A 2-fold increase in serum levels of androgens (androstenedione, testosterone, and dihydrotestosterone) was observed in women, with only a small rise in androstenedione in men. There was no change in circulating levels of sex hormone-binding globulin, estrone, or estradiol in either gender. High density lipoprotein levels declined slightly in women, with no other lipid changes noted for either gender. Insulin sensitivity and percent body fat were unaltered. Although mean 24-h GH and IGFBP-3 levels were unchanged, serum IGF-I levels increased significantly, and IGFBP-1 decreased significantly for both genders, suggesting an increased bioavailability of IGF-I to target tissues. This was associated with a remarkable increase in perceived physical and psychological well-being for both men (67%) and women (84%) and no change in libido. In conclusion, restoring DHEA and DS to young adult levels in men and women of advancing age induced an increase in the bioavailability of IGF-I, as reflected by an increase in IGF-I and a decrease in IGFBP-1 levels. These observations together with improvement of physical and psychological well-being in both genders and the absence of side-effects constitute the first demonstration of novel effects of DHEA replacement in age-advanced men and women.

The relation of smoking, age, relative weight, and dietary intake to serum adrenal steroids, sex hormones, and sex hormone-binding globulin in middle-aged men.

Abstract: The relationships of cigarette smoking, age, relative weight, and dietary intake to serum dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, cortisol, 3-alpha-androstanediol, 3-alpha-androstanediol-glucuronide, testosterone, albumin-bound testosterone, free testosterone, dihydrotestosterone (DHT), and sex hormone-binding globulin (SHBG) were examined cross-sectionally in 1241 randomly sampled middle-aged U.S. men. Compared with nonsmokers and independent of relative weight (body mass index) and age, cigarette smokers had increased serum levels of DHEA (18% higher, P = 0.0002), DHEAS (13% higher, P = 0.0007), cortisol (5% higher, P = 0.01), androstenedione (33% higher, P = 0.0001), testosterone (9% higher, P = 0.009), DHT (14% higher, P = 0.004), and SHBG (8% higher, P = 0.004). Androstenedione, total plasma testosterone, albumin-bound testosterone, DHT, and SHBG decreased with increasing relative weight. Age was positively associated with serum SHBG and negatively asso...

Induction of insulin resistance by androgens and estrogens.

Abstract: Hyperinsulinemia is a common finding in hyperandrogenic women, during pregnancy, and in women using oral contraceptives. To test whether sex hormone treatment can induce insulin resistance in healthy subjects, we studied the effects of administration of testosterone to 13 female to male and of ethinyl estradiol to 18 male to female transsexuals. Utilization and production of glucose and levels of sex steroids were measured during a three-step hyperinsulinemic-euglycemic clamp before and after 4 months of hormone administration. Females were treated with im injections of testosterone esters (250 mg/2 weeks); males were treated with ethinyl estradiol alone (0.1 mg/day, orally) or a combination of ethinyl estradiol and cyproterone acetate (100 mg/day, orally). Similar insulin levels were achieved at each of the three steps of the clamp studies before and during hormone administration. During step 1 of each clamp, with insulin levels in the physiological range, glucose utilization decreased from 3.5 +/- 1.2 to 2.6 +/- 0.9 mmol/kg lean body mass (LBM).h in women treated with testosterone esters (P < 0.001) and from 3.2 +/- 0.7 to 2.5 +/- 0.5 mmol/kg lean body mass.h in men treated with ethinyl estradiol (P < 0.001). The effects of sex steroids during steps 2 and 3 of the clamp at higher (supraphysiological) insulin levels were less clear. Endogenous glucose production (measured by isotope dilution with tritiated glucose) was not affected by hormone administration, indicating that the observed changes in glucose requirement were determined by a diminished peripheral glucose uptake. We conclude that sex hormone administration, i.e. testosterone treatment in females and ethinyl estradiol treatment in males, can induce insulin resistance in healthy subjects.

Pathogenesis of the decreased androgen levels in obese men

Abstract: In obese men, sex hormone-binding globulin levels (SHBG) as well as total plasma testosterone (T) levels are decreased. Data concerning the levels of nonprotein-bound testosterone (FT) are discordant, with some researchers reporting normal levels, and other reporting decreased levels. The latter imply an impairment of the feedback regulation mechanism of FT levels. We investigated whether an eventual decrease in FT levels and, hence, functional impairment of the gonadostat might occur only at a more severe degree of obesity than that required for a decrease in SHBG and total T levels. We, therefore, determined androgen and precursor levels in three groups of male subjects: nonobese controls [body mass index (BMI), G (kg)/L2 (m) 40; n = 22) obese men, respectively. In a subgroup of these controls, moderately and severely obese subjects, respectively, we studied LH levels as well as LH pulsatility. Moreover, as a decrease in FT levels migh...

A syndrome of female pseudohermaphrodism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutations in the gene encoding aromatase (P450arom).

Abstract: We report the features of a new syndrome of aromatase deficiency due to molecular defects in the CYP19 (P450arom) gene in a 46,XX female. At birth, the patient presented with a nonadrenal form of female pseudohermaphrodism. At 17 months of age, laparotomy revealed normal female internal genital structures; the histological appearance of the ovaries was normal. FSH concentrations were markedly elevated at 9.4 ng/mL LER 869, and estrone and estradiol levels were undetectable (< 37 pmol/L). By 14 yr of age, she had failed to exhibit breast development. The clitoris had enlarged to 4 x 2 cm, and pubic hair was Tanner stage IV. The plasma concentration of testosterone was elevated at 3294 pmol/L, as was androstenedione at 9951 pmol/L. Plasma estradiol levels were below 37 pmol/L. ACTH and dexamethasone tests indicated a nonadrenal source of testosterone and androstenedione. Plasma gonadotropin levels were in the castrate range. Pelvic sonography and magnetic resonance imaging showed multiple 4- to 6-cm ovarian...

Ovarian hyperandrogynism as a result of congenital adrenal virilizing disorders: evidence for perinatal masculinization of neuroendocrine function in women.

Abstract: Women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency often have a polycystic ovary-like syndrome, consisting of hyperandrogynism, infertility, menstrual irregularities, and elevated LH levels. This is generally considered secondary to poor control of the congenital adrenal hyperplasia. However, our experience led us to suspect that ovarian hyperandrogenism occurs even when congenital adrenal hyperplasia is well controlled on glucocorticoid therapy. Therefore, we tested the hypothesis that congenital adrenal virilizing disorders result in ovarian hyperandrogenism. We studied eight women with congenital adrenal virilizing disorders, seven with well controlled classic 21-hydroxylase deficiency and one with congenital virilizing adrenal carcinoma removed at 1.7 yr of age. We also studied six women with late-onset 21-hydroxylase deficiency, without signs of congenital virilization. An ovarian source of androgens was assessed after suppressing adrenal function with dexamethasone and then testing pituitary-ovarian function by a GnRH agonist (nafarelin) test. Five women with congenital adrenal virilizing disorders (four with classic 21-hydroxylase deficiency and one with congenital virilizing adrenal carcinoma) and one women with late-onset 21-hydroxylase deficiency had ovarian hyperandrogenism as determined by subnormal suppression of free testosterone after dexamethasone and/or by increased 17-hydroxyprogesterone response to nafarelin while on dexamethasone. All women with congenital adrenal virilization and ovarian hyperandrogenism had elevated LH levels after dexamethasone or elevated early LH response to nafarelin, which suggests that LH excess is the cause of their ovarian hyperandrogenism. This was not the case for the late-onset 21-hydroxylase-deficient woman. Our data are compatible with the hypothesis that congenital adrenal virilization programs the hypothalamic-pituitary axis for hypersecretion of LH at puberty. This is postulated to frequently cause ovarian hyperandrogenism even when adrenal androgen excess is subsequently controlled by glucocorticoid therapy.

Testosterone concentrations in women and men with NIDDM.

Abstract: OBJECTIVE To evaluate androgen concentrations in relation to insulin resistance in men and women with and without NIDDM. Recent studies have indicated the potential importance of the regulation of insulin sensitivity by androgens in both women and men. Low sex hormone binding globulin (SHBG) concentration is an independent risk factor for the development of non-insulin-dependent diabetes mellitus (NIDDM) in women and is strongly associated statistically with signs of insulin resistance. RESEARCH DESIGN AND METHODS We compared measurements of anthropometric variables and SHBG, steroid hormone, and insulin concentrations of women and men who have NIDDM with those of control subjects. RESULTS Women with NIDDM had somewhat higher plasma insulin concentrations, lower SHBG, and higher free testosterone values than did control subjects with similar body mass index (BMI). Women with NIDDM had marginally higher waist-to-hip ratios (WHR). Plasma insulin concentrations correlated positively with BMI, WHR, and free testosterone and negatively with SHBG. In multivariate analyses, insulin concentrations remained positively associated with BMI and free testosterone. Men with NIDDM had higher fasting plasma insulin concentrations than did the nondiabetic control subjects. Testosterone and SHBG were lower in the diabetic men than in both control groups. The derived value of free testosterone was not different between groups. Univariate correlation analyses revealed tight statistical couplings between plasma insulin on the one hand and SHBG and testosterone concentrations (negative) on the other. In multivariate analyses, only the insulin-testosterone association remained. CONCLUSIONS Women with NIDDM have high levels of free testosterone and low levels of SHBG. Insulin resistance is closely correlated with these signs of hyperandrogenicity as well as with obesity. Men with NIDDM also have low levels of SHBG and, in contrast to women, low testosterone values. Insulin values correlate negatively with these hormonal factors. Based on the results of experimental work and intervention studies, we suggest that these androgen abnormalities might be causally related to insulin resistance in NIDDM.

Rapid GDP release from G sα in patients with gain and loss of endocrine function

Abstract: LUTEINIZING hormone stimulates testicular Leydig cells to produce testosterone by binding to a receptor that activates the G protein Gs and adenylyl cyclase. Testotoxicosis is a form of precocious puberty in which the Leydig cells secrete testosterone in the absence of luteinizing hormone, often due to constitutive activation of the luteinizing hormone receptor and (indirectly) Gs (refs 1–4). Here we study two unrelated boys suffering from a paradoxical combination of testotoxicosis and pseudohypoparathyroidism type la (PHP-Ia)5, a condition marked by resistance to hormones acting through cyclic AMP (parathyroid hormone and thyroid-stimulat-ing hormone) as well as a 50% decrease in erythrocyte Gs activity (the remaining 50% is due to the normal Gs allele)5,6. In both patients, a mutation in the gene encoding the Gs α-subunit replaced alanine at position 366 with serine5. We show that this αs-A366S mutation constitutively activates adenylyl cyclase in vitro, causing hormone-independent cAMP accumulation when expressed in cul-tured cells, and accounting for the testotoxicosis phenotype (as cAMP stimulates testosterone secretion). Although as-A366S is quite stable at testis temperature, it is rapidly degraded at 37 °C, explaining the PHP-Ia phenotype caused by loss of Gs activity. In vitro experiments indicate that accelerated release of GDP causes both the constitutive activity and the thermolability of αs-A366S.

Metabolic and behavioral effects of high-dose, exogenous testosterone in healthy men.

Abstract: In addition to their use as replacement therapy for hypogonadal males, androgens, particularly testosterone (T), are being explored as potential hormonal male contraceptive agents, alone or in combination with other compounds. Androgens have regulatory effects on a variety of physiological systems in addition to gonadotropin secretion and spermatogenesis. Therefore, as hormonal contraceptive regiments that alter serum T levels are explored, it is important to evaluate their effects on these aspects of normal male physiology. The effects of exogenous T on suppression of spermatogenesis in 19 healthy men were recently compared, using a T dosage of 200 mg im/week for 20 weeks. Before treatment, the men were evaluated during a 3-month pretreatment period, and after treatment, they were followed for 4-6 months or until their sperm counts normalized. Because of the lack of information regarding the effects of exogenous T on nonreproductive physiology, we examined the effects of high-dose T on plasma lipids, calcium metabolism, and sexual behavior in our subjects. Mean serum T and estradiol levels increased significantly during the treatment period. Plasma high-density lipoprotein (HDL) cholesterol levels decreased significantly within the first month and remained suppressed during the duration of T administration. At the end of the treatment period, mean plasma HDL cholesterol had decreased by 13 +/- 2% (P < 0.05); plasma levels of HDL2, HDL3, and apoprotein AI also decreased significantly; mean levels of low density lipoprotein cholesterol and triglycerides were unchanged. After 1 month of the recovery period, plasma HDL levels had returned to the baseline range. Serum calcium levels decreased slightly during treatment; this decrease was statistically significant. Urinary calcium excretion did not change. Mean levels of serum intact PTH increased by 84 +/- 17% (P < 0.05) during T administration; in contrast, 25-hydroxyvitamin D levels decreased by 16 +/- 4% (P < 0.05), and 1,25-dihydroxyvitamin D levels did not change significantly. All markers of calcium metabolism returned to baseline during the posttreatment period. Little change was found in self-reported sexual and aggressive behaviors during the study. There was a trend toward increased arousal and spontaneous erections during T administration, but this did not reach statistical significance. Frequency of sexual intercourse, masturbation, and kissing and fondling did not change, nor was the subjects' satisfaction in their relationships affected by T administration. Mean body weight increased by 4.0 +/- 0.5 kg. Approximately half the men noted mild acne. Body weight and acne symptoms returned to baseline during the recovery period.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of endogenous testosterone and estradiol on sexual behavior in normal young men.

Abstract: The importance of androgens in establishing and maintaining sexual function in males of most species is well recognized. Estrogens also stimulate male sexual function in some species. In men, most studies of androgen effects on behavior have used hypogonadal men as an experimental model; much less is known about the role of endogenous testosterone (T) or estradiol (E2) in the regulation of behavior in healthy, eugonadal men. In a randomized, double-blind study, we used a GnRH antagonist, Nal-Glu, without T replacement, to induce acute, profound, reversible gonadal steroid deficiency in 9 normal men for 6 weeks (Nal-Glu alone). We also studied the effects of partial androgen replacement by administering Nal-Glu together with T enanthate, 50 mg im weekly, to 10 other men. A third group of 10 men received Nal-Glu plus T, 100 mg im weekly. We studied the role of endogenous E2 by administering Nal-Glu plus T, 100 mg im weekly, plus an aromatase inhibitor, testolactone (Teslac), 250 mg po qid, to 10 additional men (Nal - Glu + T + Teslac). Nine men received placebo injections and tablets. All subjects completed a behavioral questionnaire during the pretreatment period, at weeks 2, 4, and 6 of treatment, and at 3 weeks posttreatment. Men who received Nal-Glu alone became profoundly hypogonadal within 1 week after treatment began. Serum T levels did not change significantly in the controls and in the men who received full T replacement but decreased to approximately half the baseline level in men who received partial T replacement. E2 levels decreased profoundly in men who received Nal-Glu alone or Nal - Glu + T + Teslac and to a lesser degree in men who received partial T replacement. In men who received Nal-Glu alone, there were clinically and statistically significant decreases in the frequency of sexual desire, sexual fantasies, and intercourse at 4-6 weeks. These men also showed a strong trend (P = 0.55) towards decreased spontaneous erections after 4 and 6 weeks of treatment. A significant decrease in the frequency of masturbation was evident after 6 weeks. All measures returned to normal by posttreatment week 3. There was a trend toward increased aggression in the hypogonadal men, but this did not reach statistical significance. No changes in satisfaction or happiness with their partners were observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Distribution of androgen receptor immunoreactivity in vasopressin- and oxytocin-immunoreactive neurons in the male rat brain

Abstract: Arginine vasopressin-immunoreactive (AVP-ir) neurons in the bed nucleus of atria terminalis (BST) and medial amygdaloid nucleus are very responsive to gonadal hormones. After gonadectomy, these neurons lose their AVP immunoreactivity and stop expressing AVP mRNA. Testosterone treatment reverses these changes, acting via androgen as well as estrogen receptor-mediated mechanisms. Although AVP-ir neurons contain estrogen receptor immunoreactivity, it is not known whether they also contain androgen receptor immunoreactivity. To answer this question, brains of male rats were stained immunocytochemically for AVP as well as for androgen receptors. In the BST and medial amygdaloid nucleus, respectively, 90.5% and 91.2% of the AVP-ir neurons contained androgen receptor immunoreactivity. In contrast, in the suprachiasmatic nucleus, the supraoptic nucleus, and the magnocellular portion of the paraventricular nucleus (PVN), none of the AVP-ir neurons contained androgen receptor immunoreactivity. In the ventral zone of the medial parvocellular part of the PVN (mpvPVN), 4.3% of the scattered AVP-ir neurons contained androgen receptor immunoreactivity. One of the control experiments, Le. staining sections for oxytocin (OT) rather than AVP, revealed that although OT-ir neurons in the supraoptic and magnocellular portion of the PVN did not contain androgen receptor immunoreactivity, 52.5% of the OTir neurons in the mpvPVN did. The results suggest that androgens can bind to androgen receptors in AVP-ir neurons in the BST and medial amygdaloid nucleus, possibly to influence AVP expression. The results also suggest that androgens can bind to androgen receptors in AVP-ir and OT-ir neurons in the mpvPVN. The function of the latter interaction, however, is unclear.

Sex differences in the effects of testosterone and its metabolites on vasopressin messenger RNA levels in the bed nucleus of the stria terminalis of rats

Abstract: Male rats have about two times as many steroid-responsive vasopressin-immunoreactive (AVP-ir) neurons in the bed nucleus of the stria terminalis (BST) as female rats. This sex difference does not depend on differences in circulating hormone levels, since it persists in males and females that are treated with similar levels of testosterone. To analyze the cellular basis of this sex difference, we compared the effects of testosterone and its metabolites on AVP mRNA expression in the BST of males and females that were gonadectomized at 3 months of age. When rats received implants of Silastic tubing filled with testosterone, males had more cells that were labeled for AVP mRNA and more labeling per cell than females. When, in a second experiment, rats received implants of either empty tubing, or tubing with dihydrotestosterone (DHT), estradiol (E), or E plus DHT, hardly any labeled cells were found in rats with empty implants. E treatment significantly stimulated AVP mRNA expression in both sexes, but significantly more so in males, which had more cells that were labeled for AVP mRNA and more labeling per cell than females. DHT treatment by itself did not stimulate AVP mRNA expression, but when given in combination with E, it significantly increased the number of cells over that of animals treated with E alone. This increase was seen in males only. However, in both sexes, it increased the labeling per cell over that of animals treated with E only, but more so in males than in females. These data suggest that in addition to a sex difference in the number of cells that produce AVP there is also a sex difference in estrogen as well as androgen responsiveness in individual AVP-producing cells in the BST.

Hyperandrogenism in polycystic ovary syndrome. Evidence of dysregulation of 11 beta-hydroxysteroid dehydrogenase.

Abstract: Background Hyperandrogenemia is the hallmark of the polycystic ovary syndrome, yet the relative contributions of the adrenal cortex and ovary to the overproduction of androgen remain unclear. To identify possible causes of adrenocortical overactivity, we studied the metabolism of adrenal and ovarian steroid hormones in women with this disorder. Methods We measured 24-hour urinary excretion of steroid hormone metabolites by high-resolution capillary gas chromatography in 65 women with the polycystic ovary syndrome and 45 normal women matched for body-mass index. Results After adjustment for body-mass index, the urinary excretion of testosterone and androstenedione metabolites was 1.9 times higher in the women with the syndrome than in the normal women, and the excretion of dehydroepiandrosterone metabolites (C19 steroid sulfates) and cortisol metabolites was 1.5 and 1.3 times higher, respectively (P<0.01 for all comparisons). The affected women also had significantly higher ratios of 11-oxo (oxygenated) me...

A ten-year safety study of the oral androgen testosterone undecanoate

Abstract: Testosterone undecanoate (Andriol) is an oral androgen that provides the hypogonadal patient with the unmodified testosterone molecule It was introduced in the mid-1970s This is a report on the safety of this oral androgen Of 35 men originally included in the study, 33 could be followed up for a minimum of 10 years In them no alteration in the biochemical parameters of liver function could be detected Upon annual measurements (7-9 hours after ingestion of testosterone undecanoate), serum levels of testosterone ranged between 54 +/- 19 and 65 +/- 19 nmol/L (normal range 8-24) and of 5 alpha-dihydrotestosterone between 32 +/- 18 and 35 +/- 17 nmol/L (normal range 08-25) These levels remained constant during the study period, indicating that there is no increased hepatic enzymatic breakdown of the androgen over time Eight men were older than 50 years at the start of the study Over the 10-year period in two of them a mild reduction in urine flow was measured, whereas in the other six this could not be demonstrated Digital examination of the prostate did not reveal signs of prostate tumors Testosterone undecanoate appears to be a safe oral androgen A yearly checkup of the patient on therapy with this androgen seems adequate

Acne Vulgaris in Premenarchal Girls: An Early Sign of Puberty Associated With Rising Levels of Dehydroepiandrosterone

Abstract: Background: This study examined the relationships of pubertal maturation and sex steroid hormones to the development of acne in young girls. Black (n=317) and white (n=306) premenarchal girls with a mean age of 9.97±0.62 years were evaluated for acne prevalence and severity, pubic hair and areolar maturation, and sex steroid hormone levels. Results: Overall, 77.8% of the girls had some acne; of the whole group, 48.3% had only comedonal acne, 2.2% had only inflammatory acne, and 27.3% had both types. Although black girls matured at an earlier age than white girls, racial differences in acne were minimal when adjusted for pubertal maturation. Acne increased with advancing maturation; at Tanner pubic hair stages 1, 2, and 3, the prevalence of acne rose from 73.1% to 84.0% and to 90.6%, respectively. Acne lesion counts at seven facial locations revealed a predominance of midfacial acne on the middle aspect of the forehead, nose, and chin. Sex steroid hormone levels measured in 365 of the girls were found to increase significantly during maturation from prepuberty to early puberty. Testosterone-estrogen—binding globulin and the ratio of testosterone to estradiol decreased. In 118 prepubertal girls, estradiol, total and free testosterone, progesterone, testosterone to estradiol ratio, and testosterone-estrogen—bindingglobulin levels were no different whether in subjects with acne or without acne. However, the level of dehydroepiandrosterone sulfate, an androgen of adrenal origin, was significantly higher in prepubertal girls with acne. Conclusion: Acne, especially the comedonal type, can be the first sign of pubertal maturation in girls, even preceding pubic hair and areolar development. Concentration of dehydroepiandrosterone sulfate is significantly and specifically associated with the initiation of acne in young girls. (Arch Dermatol. 1994;130:308-314)

The direct pituitary effect of testosterone to inhibit gonadotropin secretion in men is partially mediated by aromatization to estradiol.

Abstract: In men, administration of exogenous testosterone (T) exerts direct negative feedback effects at the pituitary as well as at the hypothalamic level. This study was undertaken to determine whether T itself causes the inhibitory effects on the pituitary, or whether conversion to estradiol (E2) or dihydrotestosterone (DHT) is required. We assessed the biological activity of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as immunoactivity. Blood samples were drawn before, during, and after a continuous, 72-hour i.v. infusion of T (15 mg/day), E2 (90 micrograms/day), or DHT (500 micrograms/day). Each of these doses is twice the daily production rate of the steroid. Each man received each of the three steroid infusions. We studied four men, ages 23-35, with idiopathic hypothalamic hypogonadism (IHH), who were treated with pulsatile gonadotropin releasing hormone (GnRH) until their gonadotropins reached the normal range. Serum levels of T, E2, DHT, and levels of immunologically active and biologically active LH and FSH were measured. We found that administration of each steroid increased serum levels of the infused steroid to the upper physiologic range. Administration of T or E2 resulted in decreased mean levels of biologically and immunologically active LH and FSH; administration of DHT did not alter gonadotropin secretion. These data suggest that some of the direct effect of T at the pituitary level in men is mediated by E2, whereas peripherally formed DHT may not play an important role in this process.

Total Serum Testosterone and Gonadotropins in Workers Exposed to Dioxin

Abstract: Human reproductive endocrine data may be an important source of epidemiologic information in regard to the toxic potential of 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin). The association of serum dioxin with total serum testosterone, luteinizing hormone, and follicle-stimulating hormone was examined in 248 chemical production workers from New Jersey and Missouri plants and 231 nonexposed neighborhood referents who participated in a medical evaluation in 1987. In linear regression analyses, current serum dioxin was positively and significantly related to luteinizing hormone and follicle-stimulating hormone and inversely related to total testosterone after adjustment for potential confounders (p 28 IU/liter), high follicle-stimulating hormone (> 31 IU/liter), and low testosterone (< 10.4 nmol/liter) by serum dioxin quartiles. There was a greater prevalence of high luteinizing hormone among workers in the second (odds ratio (OR) = 1.9, 95% confidence interval (CI) 0.7-5.5), third (OR = 2.5, 95% CI 0.9-7.3), and fourth (OR = 1.9, 95% CI 0.7-5.0) quartiles of serum dioxin compared with referents. For follicle-stimulating hormone, the authors observed a greater prevalence of high follicle-stimulating hormone among workers in the fourth quartile (OR = 2.0, 95% CI 0.7-5.6) compared with referents. Similarly, the prevalence of low testosterone was two to four times greater among workers in the second (OR = 3.9, 95% CI 1.3-11.3), third (OR = 2.7, 95% CI 0.9-8.2), and fourth quartiles (OR = 2.1, 95% CI 0.8-5.8) than among referents. The trends observed in these data offer human evidence of alterations in male reproductive hormone levels associated with dioxin exposure. The results support the animal literature in which dioxin-related effects have been observed on the hypothalamic-pituitary-Leydig-cell axis and on testosterone synthesis.

Age-Related Decreased Leydig Cell Testosterone Production in the Brown Norway Rat

Abstract: Previous studies have demonstrated that Leydig cell testosterone production diminishes with age in Brown Norway rats. The objective of the studies presented herein was to test the following possible explanations for age-related decline in steroidogenesis: (1) decline in Leydig cell number; (2) understimulation by luteinizing hormone (LH); (3) reduced ability of individual Leydig cells to produce testosterone; and (4) influence of loss of germ cells. Leydig cells isolated from the testes of young and aged rats by centrifugal elutriation and Percoll density gradient centrifugation were examined for their ability to produce testosterone when stimulated maximally with LH or with dibutyryl cyclic AMP (dbcAMP). Leydig cell number and volume were examined in situ using stereological methods. Serum LH levels were measured using a highly sensitive immunofluorometric assay. Average Leydig cell volume decreased with age, and consistent with this observation, individual Leydig cells isolated from aging rats produced significantly less testosterone than those from young rats whether the cells were cultured in vitro with maximally stimulating LH or with dbcAMP. The age-associated diminished testosterone production could not be explained by changes in Leydig cell number, serum LH levels, Leydig cell responsiveness to LH, or testicular germ cell content. These results, taken together, suggest that the reduced testosterone production seen in aged rats is related to defects in the steroidogenic pathway beyond the LH receptor-cAMP cascade. The nature of the initial age-related changes that cause reduced steroidogenesis is not known, and therefore it is not known whether such changes are intrinsic or extrinsic to the Leydig cells.

Dietary supplements affect the anabolic hormones after weight-training exercise

Abstract: To examine the effect of carbohydrate and/or protein supplements on the hormonal state of the body after weight-training exercise, nine experienced male weight lifters were given water (Control) or an isocaloric carbohydrate (CHO; 1.5 g/kg body wt), protein (PRO; 1.38 g/kg body wt), or carbohydrate-protein (CHO/PRO; 1.06 g carbohydrate/kg body wt and 0.41 g protein/kg) supplement immediately and 2 h after a standardized weight-training workout. Venous blood samples were drawn before and immediately after exercise and during 8 h of recovery. Exercise induced elevations in lactate, glucose, testosterone, and growth hormone. CHO and CHO/PRO stimulated higher insulin concentrations than PRO and Control. CHO/PRO led to an increase in growth hormone 6 h postexercise that was greater than PRO and Control. Supplements had no effect on insulin-like growth factor I but caused a significant decline in testosterone. The decline in testosterone, however, was not associated with a decline in luteinizing hormone, suggesting an increased clearance of testosterone after supplementation. The results suggest that nutritive supplements after weight-training exercise can produce a hormonal environment during recovery that may be favorable to muscle growth by stimulating insulin and growth hormone elevations.

Identification of virilizing adrenal tumors in hirsute women.

Abstract: Background Hirsutism in women is usually caused by benign adrenal or ovarian disorders, but it can also be caused by adrenal carcinoma. The most effective way to identify such carcinomas is not known. Methods We measured serum and urinary steroids before and after the administration of 3 mg of dexamethasone per day for five days in 14 hirsute women with histologically proved adrenal tumors (12 adrenal carcinomas and 2 adrenal adenomas) and in 73 women with hirsutism of non-neoplastic origin. Results All the women with adrenal tumors had elevated basal serum concentrations of testosterone or dehydroepiandrosterone sulfate, as compared with 36 of the 73 women with non-neoplastic hirsutism (sensitivity, 100 percent; 95 percent confidence interval, 77 to 100; specificity, 50 percent; 95 percent confidence interval, 38 to 62). After the administration of dexamethasone, serum dehydroepiandrosterone sulfate concentrations and urinary 17-ketosteroid excretion decreased to values similar to those in normal women i...

11 beta-Hydroxysteroid dehydrogenase alleviates glucocorticoid-mediated inhibition of steroidogenesis in rat Leydig cells.

Abstract: Leydig cells from mature rat testes contain high levels of 11 beta-hydroxysteroid dehydrogenase (11HSD), an enzyme that oxidatively inactivates glucocorticoids. We have proposed that the 11HSD of Leydig cells protects the testis from the effects of high levels of glucocorticoids, as may occur in stress and Cushing's disease. In this paper we investigate whether testicular 11HSD by inactivating glucocorticoids diminishes their ability to inhibit testosterone (T) production. Corticosterone (B) and dexamethasone (DEX) inhibited T production by purified Leydig cells in a dose-dependent manner. Activity was diminished by 50% with 1.5 nM DEX vs. 0.4 microM B. The shapes of the inhibition curves were consistent with a saturable process; inhibition by both steroids was overcome with the glucocorticoid receptor antagonist RU486. We concluded that the effect was mediated by glucocorticoid receptors. Aldosterone, 11 beta-hydroxyprogesterone, and 11-deoxycorticosterone did not decrease T production. The greater poten...

A prospective study of the prevalence of clear‐cut endocrine disorders and polycystic ovaries in 350 patients presenting with hirsutism or androgenic alopecia

Abstract: Objective To determine the frequency of polycystic ovaries (PCO) on ultrasound and the incidence of clearcut endocrine disorders leading to virilization in patients complaining of hirsutism or androgenic alopecia. The major purpose was to determine a coherent policy for the routine biochemical assessment of such women. Design A prospective study of women attending a joint skin/endocrine clinic complaining of these problems. Patients Three hundred and fifty consecutive women with hirsutism and/or androgenic alopecia were assessed. Measurements Baseline endocrine screens were conducted on two occasions and included measurement of serum testosterone, androstenedione, dehydroepiandrosterone sulphate, sex hormone binding globulin, LH, FSH, 17-hydroxyprogesterone and PRL. The ovaries were visualized by high-resolution pelvic ultrasound scanning. Results Eight women were identified with relevant endocrine disorders; of these, one was acromegalic and one had a microprolactinoma--in both cases the association may have been fortuitous. Three had clear-cut 21-hydroxylase deficiency, one a rare hepatic enzyme deficiency (11-reductase), one a virilizing adrenal carcinoma and one a Leydig cell tumour. The latter six cases all had persistently elevated levels of serum testosterone (> 5 nmol/l). In all, 13 women had baseline testosterone levels in excess of 5 nmol/l. Polycystic ovaries were present in 81% of the cases who had erratic cycles and 52% of those with regular cycles; PCO were present in two of the women with 21-hydroxylase deficiency and in the woman with 11-oxoreductase deficiency. The Leydig cell tumour (1.2 cm diameter) was not detected on ultrasound or CT scan. Conclusions For the exclusion of enzyme deficiencies and virilizing tumours clinical assessment and a single serum testosterone measurement will suffice.