Showing papers on "Testosterone published in 1985"

Sex hormones, immune responses, and autoimmune diseases. Mechanisms of sex hormone action

Abstract: Immune reactivity is greater in females than in males. In both experimental animals and in man there is a greater preponderance of autoimmune diseases in females, compared with males. Studies in many experimental models have established that the underlying basis for this sex-related susceptibility is the marked effects of sex hormones. Sex hormones influence the onset and severity of immune-mediated pathologic conditions by modulating lymphocytes at all stages of life, prenatal, prepubertal, and postpubertal. However, despite extensive studies, the mechanisms of sex hormone action are not precisely understood. Earlier evidence suggested that the sex hormones acted via the thymus gland. In recent years it has become apparent that sex hormones can also influence the immune system by acting on several nonclassic target sites such as the immune system itself (nonthymic lymphoid organs), the central nervous system, the macrophage-macrocyte system, and the skeletal system. Immunoregulatory T cells appear to be most sensitive to sex hormone action among lymphoid cells. Several mechanisms of action of sex hormones are discussed in this review. The possibility of using sex hormone modulation of immune responses for the treatment of autoimmune disorders is a promising area for future investigation.

Testicular peritubular cells secrete a protein under androgen control that modulates Sertoli cell functions

Abstract: Peritubular cells of the seminiferous tubule synthesize component(s) that stimulate Sertoli cells in culture to increase the production of androgen-binding protein and testicular transferrin. The active peritubular cell component(s) are trypsin-sensitive, heat-sensitive, acid-stable molecule(s) having a molecular weight between 50,000 and 100,000. These specific factors(s) are referred to as P Mod-S to designate protein(s), produced by peritubular cells (P), that modulate the functions of Sertoli cells (S). The degree of stimulation by P Mod-S is comparable to that obtained by maximal hormonal stimulation of the synthesis of ABP and transferrin by Sertoli cells. Levels of P Mod-S secreted into the medium by primary cultures of peritubular cells are increased in the presence of testosterone. Comparable concentrations of 17 beta-estradiol do not stimulate peritubular cells to synthesize P Mod-S. Data are interpreted to indicate that androgens act on testicular peritubular cells to increase the formation of P Mod-S and that P Mod-S may modulate the properties of adjacent Sertoli cells. Findings are discussed in relation to the nature of mesenchymal-epithelial cell interactions in the seminiferous tubule and to the possible role of P Mod-S as a mediator of androgen actions of Sertoli cells.

Fat Tissue: A Steroid Reservoir and Site of Steroid Metabolism

Abstract: Sex steroid concentrations and 17 beta-hydroxy-steroid dehydrogenase and aromatase activities were determined in fat tissue removed at surgery or, in order to allow comparisons in different sites, postmortem. Except for dehydroepiandrosterone (DHEA) sulfate (DHEAS), there existed a positive tissue/plasma gradient for all steroids studied (testosterone, androstenedione, DHEA, androstenediol, estrone, and estradiol), suggesting androgen uptake and estrogen synthesis in situ. Androgen concentrations did not vary according to site of origin of fat tissue, except that the DHEAS concentration was significantly lower in abdominal sc and omental fat than in breast, pericardial, or sc pubic fat. Tissue androgen concentrations were positively correlated with their plasma concentrations, but tissue and plasma estrogen concentrations were not correlated. All tissue steroid concentrations, with the exception of estradiol in men, decreased with age. Aromatase activity [androstenedione----estrone; mean maximum velocity, 7.4 +/- 3.7 (+/- SD) fmol estrone/mg protein . h] did not vary between sexes or with site of origin of fat tissue. 17 beta-Hydroxysteroid dehydrogenase activity (estradiol----estrone, mean maximum velocity 9.8 +/- 5.4 pmol/mg protein . h) was higher in fat from women than in that from men, higher in premenopausal than in postmenopausal women, and higher in omental than in sc fat. Its activity was noncompetitively inhibited in vitro by DHEA and DHEAS in near-physiological concentrations, and the enzyme activity was inversely correlated (P less than 0.001) with the tissue DHEA and DHEAS concentrations. We conclude that fat tissue is an important steroid hormone reservoir, that it is the site of active aromatase and 17 beta-hydroxysteroid dehydrogenase, and that tissue DHEA(S) may have a modulating effect on tissue estrogen production.

Late-Onset Adrenal Steroid 3β-Hydroxysteroid Dehydrogenase Deficiency. I. A Cause of Hirsutism in Pubertal and Postpubertal Women

Abstract: To investigate the adrenal cause of hyperandrogenism in peri- and postpubertal hirsute women, baseline and ACTH-stimulated serum concentrations of delta 5-17-hydroxypregnenolone (delta 5-17P), dehydroepiandrosterone (DHEA) and its sulfate, 17-hydroxyprogesterone (17-OHP), cortisol, delta 4-androstenedione, and testosterone were determined in 116 women with hirsutism or acne of peri- and postpubertal onset with or without menstrual abnormalities. The results were compared with the same steroid concentrations in 30 normal age-matched women. Sixteen of the 116 women with hirsutism whose ACTH-stimulated 17-OHP levels (mean +/- SD, 5404 +/- 3234 ng/dl; normal, 334 +/- 194) were markedly elevated while their ratios of delta 5-17P to 17-OHP (0.4 +/- 0.2; normal, 3.4 +/- 1.5) were low were diagnosed as having nonclassical symptomatic 21-hydroxylase deficiency. Seventeen other hirsute women, including 3 siblings, had very high responses of delta 5-17P (2276 +/- 669 ng/dl; normal, 985 +/- 327) and DHEA (2787 +/- 386 ng/dl; normal, 1050 +/- 384) to ACTH stimulation, with significantly elevated ratios of delta 5-17P to 17-OHP (11 +/- 2.0; normal, 3.4 +/- 1.5) and DHEA to delta 4-androstenedione (7.5 +/- 2.3; normal, 4.6 +/- 1.5). In these hirsute women, the morning serum delta 5-17P and DHEA concentrations were elevated, had a diurnal variation, and were suppressed with dexamethasone administration. We propose that partial adrenal 3 beta-hydroxysteroid dehydrogenase deficiency is the cause of hirsutism in these women. This may represent an allelic variant at the genetic locus for 3 beta-hydroxysteroid dehydrogenase deficiency similar to that reported for symptomatic nonclassical 21-hydroxylase deficiency producing peripubertal excess androgen syndrome.

Influence of perinatal androgen on the sexually dimorphic distribution of tyrosine hydroxylase-immunoreactive cells and fibers in the anteroventral periventricular nucleus of the rat.

Abstract: Recently we reported that the anteroventral periventricular nucleus (AVPv) of the preoptic region contains a dramatic sexual dimorphism in the distribution of tyrosine hydroxylase- (TH-)immunoreactive cells and fibers in the rat. This sexual dimorphism appears to be due to a greater density of dopaminergic fibers, and a larger number of dopaminergic cell bodies, in the AVPv of the female. In the present study we used an indirect immunohistochemical method to evaluate the distribution of TH-immunoreactive cell bodies and fibers, and of dopamine-β-hydroxylase-(DBH-)stained fibers, in the AVPv of female rats that were treated with testosterone propionate (TP) perinatally or postnatally, or were left untreated. All of the postnatally TP-treated animals failed to show a phasic pattern of luteinizing hormone (LH) secretion in response to estrogen and progesterone injections. Both the perinatally and postnatally TP-treated females had polyfollicular ovaries that lacked corpora lutea at the time of gonadectomy. Perinatal TP exposure resulted in what appears to be a complete masculinization of both the number of TH-stained cells and the density of TH-stained fibers in the AVPv. The number of TH-stained cells in the postnatally TP-treated females was also completely masculinized, although the density of TH-stained fibers did not appear to be altered significantly. Gonadectomy resulted in a moderate increase in the density of TH-stained fibers in adult males, and did not significantly affect the fiber density in females, or the number of TH-stained cells in either sex. The distribution of DBH-stained fibers in the AVPv did not appear to be altered in any of the treatment groups. These results suggest that the distribution of dopaminergic fibers in the AVPv may be sensitive to testosterone levels in the adult male, and that although the critical period for the development of this fiber distribution may begin in the prenatal period, the number of dopaminergic cells in the AVPv can be completely sex reversed by a single postnatal dose of TP that appears to correlate with a permanent disruption of the normal pattern of gonadotropin secretion.

Androgens, behaviour and nocturnal erection in hypogonadal men: the effects of varying the replacement dose.

Abstract: SUMMARY The behavioural effects of varying the replacement dose of the oral androgen testosterone undecanoate (TU, Restandol) were investigated in eight hypogonadal men. Each man was withdrawn from his previous androgen replacement regimen and after a period of no treatment was administered four doses of TU (40, 80, 120 and 160 mg/d) in four successive one-month treatment periods using a double-blind design. Throughout the study each man recorded his sexual interest, behaviour and mood state using a daily diary form. In addition, four hypogonadal subjects had sleep erections and sleep quality assessed in the laboratory during a state of androgen withdrawal and again after a minimum of 5 months of androgen treatment. A dose response relationship was demonstrated for frequency of sexual thoughts, arousal accompanying sexual thoughts and well-being. Sleep erections improved significantly during testosterone administration. In men, sexual interest and sleep erections are androgen-dependent.

Age-related alteration in the activities of drug-metabolizing enzymes and contents of sex-specific forms of cytochrome P-450 in liver microsomes from male and female rats.

Abstract: Age-related changes in the amounts of sex-specific forms of cytochrome P-450 as well as the activities of drug-metabolizing enzymes in liver microsomes of Fischer-344 rats of different ages ranging from 3 to 30 months were studied. Activities of 7-propoxycoumarin O-depropylase and benzo(a)pyrene hydroxylase in male rats, which were higher than those in female rats in younger adults (3-12 months), decreased with increasing age, resulting in the loss of sex differences after 25 months. The male-specific form of cytochrome P-450, namely P-450-male, present in younger adults, was not detectable in older ages. In old male rats, the female-specific form of cytochrome P-450, namely P-450-female, appeared instead of P-450 male. In liver microsomes of young and old female rats, rather constant levels of P-450-female were observed, whereas P-450-male was not detectable. Serum concentrations of testosterone and estradiol were also quantitated. The ratio of testosterone to estradiol concentrations decreased with age in male rats whereas the ratio was not changed in female rats. Based on these results, we propose that the age-related decrease in the activities of drug-metabolizing enzymes in male rats is attributable to the change in the population of cytochrome P-450, especially P-450-male and P-450-female, probably owing to the alteration of the levels of gonadal hormones.

Somatomedin-C in normal puberty and in true precocious puberty before and after treatment with a potent luteinizing hormone-releasing hormone agonist

Abstract: To explore further the relationship of gonadal sex steroids to the rise in somatomedin-C (Sm-C) during puberty, we studied a group of children with true precocious puberty before and after treatment which suppressed sex steroid output. Plasma estradiol and testosterone and serum acid-ethanol-extractable Sm-C were determined by specific RIAs in 7 boys and 12 girls with true precocious puberty before and at regular intervals during treatment with a potent LHRH-agonist (LHRH-A), D-Trp6-Pro9-NEt-LHRH. For comparison, Sm-C and sex steroid concentrations were determined in 266 normal adolescents and 37 normal prepubertal children, 1-9 yr of age. The mean +/- SEM Sm-C levels in normal male individuals peaked at 15 yr (2.46 +/- 0.23 U/ml) and at pubertal (genital) stage III (2.29 +/- 0.19 U/ml), and those in normal females reached their highest concentration at 12-15 yr of age and at pubertal (breast) stage III (2.47 +/- 0.15 U/ml). Sm-C concentrations correlated better with pubertal (genital or breast) stage than with chronological age for both sexes and better with testosterone levels in males than with estradiol levels in females. The mean +/- SEM Sm-C concentrations in both males and females with true precocious puberty were 2.07 +/- 0.16 U/ml before therapy and decreased significantly to 1.52 +/- 0.13 U/ml after 6 months of therapy. The mean Sm-C level of the patients remained significantly elevated for chronological age, but decreased into the normal range for bone age after 6-12 months of therapy. Sm-C correlated significantly with testosterone and estradiol levels, but not with growth rate. Mean nighttime GH secretion decreased significantly after 6 months of LHRH-A therapy. In summary, children with true precocious puberty have Sm-C elevations typical of normal puberty. The decrease in Sm-C levels after suppression of gonadal sex steroid output with LHRH-A is evidence that sex steroids are necessary to induce this elevation in Sm-C concentration. The decrease in GH secretion during LHRH-A therapy suggests that the effect of sex steroids on Sm-C levels during normal puberty is mediated, at least in part, through stimulation of GH secretion.

Concentrations of steroids and gonadotropins in follicular fluid from normal heifers and heifers primed for superovulation.

Abstract: The concentrations of six steroids and of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured in follicular fluid from preovulatory and large atretic follicles of normal Holstein heifers and from preovulatory follicles of heifers treated with a hormonal regimen that induces superovulation. Follicular fluid from preovulatory follicles of normal animals obtained prior to the LH surge contained extremely high concentrations of estradiol (1.1 +/- 0.06 micrograms/ml), with estrone concentrations about 20-fold less. Androstenedione was the predominant aromatizable androgen (278 +/- 44 ng/ml; testosterone = 150 +/- 39 ng/ml). Pregnenolone (40 +/- 3 ng/ml) was consistently higher than progesterone (25 +/- 3 ng/ml). In fluid obtained at 15 and 24 h after the onset of estrus, estradiol concentrations had declined 6- and 12-fold, respectively; androgen concentrations had decreased 10- to 20-fold; and progesterone concentrations were increased, whereas pregnenolone concentrations had declined. Concentrations of LH and FSH in these follicles were similar to plasma levels of these hormones before and after the gonadotropin surges. The most striking difference between mean steroid levels in large atretic follicles (greater than 1 cm in diameter) and preovulatory follicles obtained before the LH surge was that estradiol concentrations were about 150 times lower in atretic follicles. Atretic follicles also had much lower concentrations of LH and slightly lower concentrations of FSH than preovulatory follicles. Hormone concentrations in follicles obtained at 12 h after the onset of estrus from heifers primed for superovulation were similar to those observed in normal preovulatory follicles at estrus + 15 h, except that estrogen concentrations were about 6-40 times lower and there was more variability among animals for both steroid and gonadotropin concentrations. Variability in the concentrations of reproductive hormones in fluid from heifers primed for superovulation suggests that the variations in numbers of normal embryos obtained with this treatment may be due, at least in part, to abnormal follicular steroidogenesis.

Pituitary-gonadal function in Klinefelter syndrome before and during puberty.

Abstract: Serum concentrations of follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol were determined at intervals before and during puberty in 40 individuals with Klinefelter syndrome (47,XXY karyotype), of whom 27 had been detected in neonatal cytogenetic screening programs. Prior to the appearance of secondary sexual changes, basal serum hormone concentrations and acute responses to stimulation with gonadotropin-releasing hormone and human chorionic gonadotropin were normal. The timing of the onset of clinical puberty was normal. Early pubertal boys showed initial testicular growth and normal serum testosterone levels, while serum follicle-stimulating hormone and estradiol concentrations were significantly elevated. By midpuberty, the Klinefelter subjects were uniformly hypergonadotropic and their testicular growth had ceased. Serum testosterone concentrations after age 15 remained in the low-normal adult range. Serum estradiol levels remained high, irrespective of the presence or absence of gynecomastia. Exaggerated responses to gonadotropin-releasing hormone are seen in pubertal subjects with elevated basal gonadotropin values.

The frequency of gonadotropin-releasing hormone stimulation determines the number of pituitary gonadotropin-releasing hormone receptors.

Abstract: Gonadotropin-releasing hormone (GnRH) induces both synthesis and release of pituitary gonadotropins, but rapid or slow frequencies of stimulation result in reduced LH and FSH secretion. We determined the effects of frequency of GnRH stimulation on pituitary GnRH receptors (GnRH-R). Castrate male rats received testosterone implants (cast+T) to inhibit endogenous GnRH secretion. GnRH pulses were injected by a pump into a carotid cannula and animals received GnRH (25 ng/pulse) at various frequencies for 48 h. In control animals (saline pulses) GnRH-R was 307+21 fmol/mg protein (+.SE) in cast+T and 598+28 in castrates. Maximum GnRH-R was produced by 30-min pulses and was similar to that seen in castrate controls. Faster or slower frequencies resulted in a smaller GnRH-R response and GnRH given every 240 min did not increase GnRH-R over saline controls. Equalization of the total GnRH dose/48 h (6.6 ng/pulse every 7.5 min or 200 ng/pulse every 240 min) did not increase receptors to the maximum concentrations se...

Tissue production of androgens in women with acne

Abstract: Precursor and target tissue-produced androgens were measured in the plasma of eighteen women with mild to moderate acne. Mean plasma levels of the precursor androgens (total testosterone, free testosterone, androstenedione, and dehydroepiandrosterone sulfate) were similar to levels in a group of carefully selected acne-free and hirsute-free, age-matched female controls. In contrast, plasma 3α-androstanediol glucuronide (3α-diol G) values were elevated in 13 of the patients, with a mean value for the entire group nearly threefold that of the normal controls (117 vs 43 ng/dl; p

Identification of insulin-like growth factor-I and its receptors in the rat testis.

Abstract: As part of a study of the testicular production and action of insulin-like growth factor-I (IGF-I), adult rat testes were extracted with acidified methanol, yielding an immunoreactive IGF-I fraction corresponding in size to human IGF-I. The mean IGF-I content (+/- SEM) of testes weighing approximately 1.1 g was 51.5 +/- 5.6 ng/testis, and was not due to serum contamination. After a 3-day fast testicular IGF-I decreased by 80%, whereas serum IGF-I levels declined by 90%. Testicular homogenates and isolated Leydig cells were shown to contain specific IGF-I receptors, Ka = 2 X 10(9) M-1, with 10% IGF-II cross-reactivity. The concentration of these receptors was 2 pmol binding sites per testis, or 3.3 fmol per 10(6) Leydig cells. However IGF-I at 250 ng/ml had no effect on basal or hCG-stimulated testosterone production by isolated Leydig cells, measured over 3 h. Although an effect of IGF-I over longer incubation periods cannot be excluded, it is also possible that testicular IGF-I has a mitogenic role, rather than acting on differentiated testicular functions.

Effects of testicular macrophage-conditioned medium on Leydig cells in culture.

Abstract: Conditioned medium from cultures of testicular macrophages was capable of stimulating testosterone production in a dose-dependent manner when added to Leydig cells in vitro. Significant stimulation of testosterone production by Leydig cells was observed after 4 h of exposure to testicular macrophage-conditioned medium (TMCM) and thereafter increased progressively for up to 24 h. Treatment of Leydig cells with TMCM together with a maximal dose of LH resulted in greater production of testosterone by Leydig cells than with either agent when used separately. Conditioned medium from macrophages treated with FSH was twice as potent as TMCM from untreated cells. This dose of FSH had no direct effect on Leydig cells. Conditioned medium from cultures of peritoneal macrophages had less effect on testosterone production by Leydig cells than testicular macrophage-conditioned medium. It is proposed that secretory products from testicular macrophages play an important role in testicular function.

Specific destruction of Leydig cells in mature rats after in vivo administration of ethane dimethyl sulfonate.

Abstract: Effects of ethane dimethyl sulfonate (EDS) on Leydig cells have been studied using the following parameters: morphology, histochemistry of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and esterase, quantitative activity of esterase, testosterone concentrations in plasma, and steroid production by isolated interstitial cells in vitro. Degenerating Leydig cells were observed within 16 h after the injection of mature rats with EDS (75 mg/kg body weight). At that time the testosterone concentration in plasma and the specific activity of esterase in testis tissue were decreased to approximately 35% and 60% of the control value, respectively. At 48 h after EDS only a few normal Leydig cells were left and the plasma testosterone concentration was less than 5% of the control value. The specific activity of esterase in total testis tissue was similar to the activity of dissected tubules from untreated rats. At 72 h no Leydig cells could be detected and no 3 beta-HSD and esterase-positive cells were present. At that time macrophages were still present in the interstitium and the appearance of the spermatogenic epithelium was normal, but 1 wk after EDS the elongation of spermatids was disturbed, probably due to a lack of testosterone. In some of the animals the cytotoxic effects of EDS on Leydig cells could be partly inhibited by human chorionic gonadotropin treatment. The basal steroid production by interstitial cells from mature rats 72 h after EDS was not significant and no stimulation by LH was observed, whereas no effect of EDS could be detected on steroid production by interstitial cells isolated from immature rats and mice 72 h after treatment. Other compounds with similar structures, such as butane dimethyl sulfonate (busulfan) and ethane methyl sulfonate (EMS) had no effect on Leydig cells from mature rats. It is concluded that EDS specifically destroys Leydig cells in mature rats.

Treatment of True Precocious Puberty with a Potent Luteinizing Hormone-Releasing Factor Agonist: Effect on Growth, Sexual Maturation, Pelvic Sonography, and the Hypothalamic-Pituitary-Gonadal Axis

Abstract: We used the LHRH agonist D-Trp6-Pro6-N-ethylamide LHRH (LHRH-A) to treat 19 children (12 girls and 7 boys) with true precocious puberty. Fourteen patients had idiopathic true precocious puberty, 4 had a hamartoma of the tuber cinereum, and 1 had a hypothalamic astrocytoma. Basal gonadotropin secretion and responses to native LHRH decreased within 1 week of initiation LHRH-A therapy, and sex steroid secretion decreased within 2 weeks to or within the prepubertal range. Ultrasonographic evaluation of the uterus indicated a postmenarchal size and shape in all 11 girls studied before treatment, which reverted to prepubertal size and configuration in 5 girls during LHRH-A therapy. The enlarged ovaries decreased in size and the multiple ovarian follicular cysts regressed. Sexual characteristics ceased advancing or reverted toward the prepubertal state in all patients receiving therapy for 6-36 months. All 5 girls with menarche before therapy had no further menses. Three girls had hot flashes after LHRH-A-induced reduction of the plasma estradiol concentration. Height velocity, SDs above the mean height velocity for age, and SDs above the mean height for age decreased during LHRH-A therapy; the velocity of skeletal maturation decreased after 12 months of LHRH-A therapy and was sustained during continued therapy over 18-36 months. In 4 patients, a subnormal growth rate (less than 4.5 cm/yr) occurred during LHRH-A therapy. Six patients had cutaneous reactions of LHRH-A, but no demonstrable circulating antibodies to LHRH-A. In 2 patients in whom LHRH-A therapy was discontinued because of skin reactions, precocious sexual maturation resumed at the previous rate for the ensuing 6-12 months; subsequently, they were desensitized to LHRH-A, and during a second course of therapy, their secondary sexual development and sex steroid levels again quickly decreased. LHRH-A proved an effective and safe treatment for true precocious puberty in boys as well as girls with central precocious puberty whether of the idiopathic type or secondary to a hamartoma of the tuber cinereum or a hypothalamic neoplasm.

Response of serum hormones to androgen administration in power athletes.

Abstract: Endocrine effects of self-administration of high doses of anabolic steroids and testosterone were investigated in five power athletes during 26 wk of training, and for the following 12–16 wk after drug withdrawal. After 26 wk of anabolic steroid and testosterone administration, serum testost

Androgen and estrogen receptors in fetal rhesus monkey brain and anterior pituitary.

Abstract: In this study, we sought to identify and characterize cytosolic androgen and estrogen receptors in the brain and anterior pituitary gland (AP) of fetal rhesus monkeys using the technique of DNA-cellulose chromatography. Cytosolic extracts were prepared from fetal monkey (days 135–162 of gestation) tissues including hypothalamus-preoptic area/amygdala (HPOA/AMG), cerebral cortex, and AP. Extracts were incubated with [3H]testosterone, [3H]5α-dihydrotestosterone,or [3H] 17/3-estradiol and applied to DNA-cellulose columns. [3H]Androgen- and [3H]estrogen-binding activities from cytosolic extracts adhered to DNA-cellulose. After elution with a linear salt gradient (10–500 mm NaCl) [3H]androgen-binding activity exhibited elution maxima between 130–150 mm NaCl, while [3H] estrogen-binding activity exhibited elution maxima between 200–220 mm NaCl. These elution patterns were similar in every region examined and were characteristic of putative androgen and estrogen receptors found in other vertebrate species. Addit...

Abnormal androgen and oestrogen metabolism in men with steroid sulphatase deficiency and recessive x‐linked ichthyosis

Abstract: Serum levels of sex hormone binding globulin (SHBG), testosterone, free testosterone, dihydrotestosterone, androstenedione, dehydroepiandrosterone sulphate, oestradiol, oestrone, oestrone sulphate, FSH, and LH were measured in 20 steroid sulphatase-deficient men with recessive X-linked ichthyosis and in normal men. The serum oestrone sulphate level was significantly higher than normal in the patients (P less than 0.0001). In affected men, there was a tendency towards higher dehydroepiandrosterone sulphate levels and no decline with age was seen in the patients as opposed to normal men (interaction: P less than 0.025). Serum androstenedione, and oestradiol levels were lower than normal in the patients (P less than 0.0005 and P = 0.055, respectively), while their LH level was higher than normal (P less than 0.0005). The serum levels of SHBG, total and free testosterone, dihydrotestosterone, oestrone, and FSH were not significantly different from normal in the icthyotic patients. We suggest that the observed abnormalities in these patients are a consequence of the enzyme deficiency which severely impairs the ability of tissues to hydrolyse steroid sulphates.

Familial factors affecting prostatic cancer risk and plasma sex-steroid levels

Abstract: Whether familial factors affect the frequency of prostatic cancer and the plasma content of sex-steroids was investigated. Brothers (n = 257) of probands (n = 150) diagnosed with prostatic cancer before age 62 years had a fourfold higher risk for developing the disease than men in the general population in the State of Utah and their brothers-in-law (n = 202). Familial factors markedly affected the plasma content of sex steroids (testosterone, dihydro-testosterone, the ratio of testosterone to DHT, sex-hormone binding globulin, and the free fraction of testosterone) in nonendocrinologically treated probands and their brothers and sons and in normal men in the general populations. Index cases and their brothers and sons had a significantly lower mean plasma testosterone content than controls of comparable age. Preliminary data suggest that the metabolic clearance rate of testosterone and the conversion ratio of testosterone to estradiol are relatively high in probands. The observations indicate that familial factors are potent risk factors for the development of prostatic cancer. They also suggest that plasma androgen values in families with prostatic cancer cluster in the lower range of normal and that plasma sex-steroid content is more similar in each brothers with or without prostatic cancer than among nonbrothers.

The Development of a Male Pseudohermaphroditic Rat Using an Inhibitor of the Enzyme 5α-Reductase

Abstract: Incomplete masculinization of the external genitalia occurred in male Sprague-Dawley rats treated with a potent inhibitor of enzyme 5 alpha-reductase at the critical period of sexual differentiation in utero. The studies were performed using the 5 alpha-reductase inhibitor, 4-methyl-4-aza-5-pregnan-3-one-20[s] carboxylate, one of a series of aza steroids known to competitively inhibit the enzyme 5 alpha-reductase. The degree of inhibition of male external genital development was dependent upon the dose of the inhibitor, and at a dose of 36 mg/kg X day, there was complete feminization of the external genitalia of the male animal with a urogenital sinus and a pseudovagina. These studies provide conclusive evidence for the hypothesis that 5 alpha-reductase activity and dihydrotestosterone (17 beta-hydroxy-5 alpha-androstan-3-one) formation are essential for normal differentiation of male external genitalia. Epididymidis, vasa deferentia, and seminal vesicles were present at all doses of the inhibitor, suggesting testosterone dependency. However, confirmation of the testosterone dependency of Wolffian ductal differentiation awaits further studies, particularly comparison studies with the rabbit and dog, since Wolffian ductal differentiation in the rat, unlike the rabbit and dog, is not abolished with the antiandrogen, cyproterone acetate. The presence of prostatic buds, despite complete external genital feminization, was unexpected and suggests that these structures may have different thresholds of response for dihydrotestosterone. Prostatic differentiation may have a much lower threshold, requiring less dihydrotestosterone for differentiation.

Puberty in the chimpanzee: somatomedin-C and its relationship to somatic growth and steroid hormone concentrations.

Abstract: A relationship between sex steroids and the somatomedins (Sms) is well known, but poorly defined. In some primates, including man, there are pubertal increases in Sms, concurrent with increased growth and sex steroid production. In the current studies, indices of somatic growth [body weight, crown-rump length (CRL), and testis size (testicular volume index)] and circulating concentrations of testosterone (T), estradiol (E2), dehydroepiandrosterone sulfate (DHEA-S), cortisol, and Sm-C were determined (n x003D; 208) in 86 male and female chimpanzees during a 1-yr period. In addition, we have attempted to determine whether plasma Sm-C concentrations correlate with serum levels of estrogen and androgens.In male animals between 6 and 8 yr of age, there was a marked increase in testicular size, concurrent with an increase in serum T and preceding slightly an increase in the rate of body weight gain. There were no detectable increases in serum E2 or theCRL slope. In females between 6 and 8 yr of age, serum T inc...