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S J Winters

Publications and source records attributed to S J Winters.

At least 91 records · Page 5Linked to original sources
PubMed1984

Evidence for an androgen receptor in the seminiferous tubules of the human testis.

Androgen receptors (AR) were studied in seminiferous tubule cytosol and testicular nuclear extracts prepared from testes of previously untreated elderly men undergoing orchiectomy as therapy for prostatic carcinoma. Cytosol exhibited high affinity (Kd = 0.8 nM), saturable binding of [3H]methyltrienolone; however, the synthetic progestin, promegestone was a stronger competitor for MT binding sites than were 5 alpha-dihydrotestosterone (DHT) or testosterone (T), suggesting the presence of progesterone-like binding sites. Addition of triamcinolone acetonide (TA) produced the usual relative steroid specificity for AR binding and reduced the measured AR binding capacity by 19 +/- 8% (Mean +/- SD, n = 3). The umber of MT binding sites was 30-40 fmol/mg protein, or an average of 65 fmol/g testis, and the equilibrium dissociation constant at 0 degrees C was 0.6-1.4 nM. In the presence of sodium molybdate, binding was stable for 40 h at 0 degrees C and the half-time of dissociation of the MT-AR complex was 12-16 h. The binding of salt extractable (600 mM KCl) nuclear sites to MT was saturable and was specific for androgens. The number of binding sites in nuclear extracts was 170 fmol/g testis and the apparent equilibrium dissociation constant was 4.2 nM. Thus, the binding of MT to human seminiferous tubule cytosol and testicular nuclear extract exhibits properties which are nearly identical to those of the prostate AR. Further study of this androphilic protein may provide insight into the role of androgen in normal and abnormal spermatogenesis in man.

Cell Nucleus↗
PubMed1984

The gonadotropin-suppressive activity of androgen is increased in elderly men.

The influence of aging on the responsiveness to sex steroid hormones in men was studied by comparing circulating gonadotropin concentrations, pulsatile LH release, and sex hormone-binding globulin (TeBG) levels. This was done before and during a four-day continuous infusion of testosterone (T) (7.5 mg/d), dihydrotestosterone (DHT) (7.0 mg/d), or estradiol (E2) (45 micrograms/d) in young adult men, ages 18 to 32, and healthy elderly men, ages 65 to 80. DHT reduced mean serum LH and FSH levels as well as the frequency of spontaneous LH secretory episodes to a greater extent (p less than 0.05) in old men than in young men. T administration also reduced serum LH levels more in aged than in young men (P less than 0.05); however, this difference was less pronounced than for DHT. During T infusion, the decrease in serum FSH levels was similar in the two groups. Spontaneous LH pulse amplitude also declined during both T and DHT infusion in aged, but not in young men. By contrast, infusion of E2 reduced both serum LH and FSH levels comparably in aged and young men. DHT infusion also reduced serum TeBG levels equally in old and young men. Finally, each steroid infusion produced comparable mean circulating levels of T, DHT, and E2 in both groups. These data indicate that elderly men are more responsive than are young men to the gonadotropin-suppressive effects of androgen, but not to DHT effects on circulating TeBG levels. The more pronounced deceleration of spontaneous LH secretory episodes during DHT infusion in aged men provides evidence for an alteration in hypothalamic function in male senescence.

Aged↗
PubMed1984

Basal and adrenocorticotropic hormone-stimulated serum 17 alpha-hydroxyprogesterone in men with idiopathic infertility.

Basal serum 17 alpha-hydroxyprogesterone (17-OHP) concentrations and the 17-OHP response to acute adrenocorticotropic hormone administration were studied in infertile men with idiopathic oligospermia to determine the prevalence of attenuated 21-hydroxylase deficiency. Mean (+/- standard error of the mean) basal serum 17-OHP levels in 50 infertile men (1.17 +/- 0.06 ng/ml) and 25 normal volunteers (1.09 +/- 0.08 ng/ml) were indistinguishable (not significant). However, two infertile men had 17-OHP levels which were above the normal range. Following the intravenous administration of 0.25 mg of synthetic adrenocorticotropic hormone (cosyntropin) to these two men and to eight additional infertile men, the mean increase in 17-OHP concentrations was 0.84 +/- 0.15 ng/ml, a response which was similar to that of normal men (0.94 +/- 0.26 ng/ml). No patient demonstrated the minimum fourfold rise in 17-OHP previously reported in men with attenuated 21-hydroxylase deficiency, suggesting the absence of this disorder among these subjects. This study suggests that subtle 21-hydroxylase deficiency is rare among infertile men with idiopathic infertility.

17-alpha-Hydroxyprogesterone↗
PubMed1984

Altered pulsatile secretion of luteinizing hormone in hypogonadal men with hyperprolactinaemia.

To explore the mechanism for the hypogonadism associated with prolactin hypersecretion in men we examined luteinizing hormone (LH) secretory profiles in four hyperprolactinaemic men before and during treatment with bromocriptine. Pretreatment serum prolactin levels were increased 4-100 fold and serum testosterone levels were low in three men and low-normal in the fourth subject. Mean LH levels were low-normal and the frequency of spontaneous LH secretory episodes was less than normal in three of four men. Bromocriptine reduced serum prolactin levels to normal; subsequently, serum testosterone levels increased and libido and potency improved markedly in each man. The rise in serum testosterone levels was associated with an increase in mean LH concentrations and in LH pulse frequency. Mean follicle-stimulating hormone levels also increased during bromocriptine treatment. Insofar as each LH pulse is believed to reflect a discharge of gonadotrophin releasing hormone from the anterior hypothalamus, our data suggest that a major abnormality in hyperprolactinaemic men with hypogonadism is a disorder of the neuroregulatory mechanism for pulsatile gonadotrophin-releasing hormone secretion.

Adult↗
PubMed1983

Studies of the human testis. XVIII. Simultaneous measurement of nine intratesticular steroids: evidence for reduced mitochondrial function in testis of elderly men.

To determine the basis for the decline in testosterone production by the aged testis, intratesticular unconjugated steroids, including testosterone, pregnenolone (3 beta-hydroxy-5-pregnen-20-one), 17 alpha-hydroxypregnenolone (3 beta,17 alpha-dihydroxy-5-pregnen-20-one), dehydroepiandrosterone (3 beta-hydroxy-5-androsten-17-one), androstenediol (5-androstene-3 beta,17 beta-diol), progesterone, 17 alpha-hydroxyprogesterone, androstenedione (4-androstene-3,17-dione), and 17 beta-estradiol, were measured by simultaneous RIAs in 32 previously untreated elderly men (aged 61-85 yr) undergoing orchiectomy as therapy for prostatic carcinoma and 20 young men (aged 25-35 yr) with oligospermia and varicocele. In vitro steroidogenesis using labeled pregnenolone as substrate was also investigated. Serum and intratesticular testosterone levels were lower (P less than 0.05) in aged patients [3.3 +/- 1.9 ng/ml and 0.86 +/- 0.53 microgram/g tissue (mean +/- SD)] than in young men (6.4 +/- 1.9 ng/ml and 1.7 +/- 1.1 microgram/g tissue), while circulating LH levels were higher (P less than 0.05) in elderly men (151 +/- 105 ng/ml) than in the young men (79 +/- 33 ng/ml), indicating that a primary pathological process affects the senescent testis, producing a decline in testosterone production. Study of bioconversion of [3H]pregnenolone to delta 4 steroids, 17 alpha-hydroxysteroids, and C19 steroids as well as analysis of the relative amounts of intratesticular steroids, as determined by RIA, revealed no apparent differences in the process of microsomal steroidogenesis in elderly compared to that in young men. The sum of the nine measured intratesticular steroid concentrations per g tissue wt was significantly lower (P less than 0.05) in aged patients (1.94 +/- 0.93 microgram/g tissue), than in young patients (3.68 +/- 1.90 micrograms/g tissue). The sum of the nine intratesticular steroids measured was positively correlated (P less than 0.01) with circulating LH levels in both patient groups, and the slope of this regression line was 14-fold greater for young men than for elderly men. Since the total concentration of the nine measured steroids reflects the pregnenolone supplied by the mitochondria within Leydig cells, it appears that the decline in Leydig cell function in aged men is attributable to a reduced supply of mitochondrial steroid precursors rather than to an impairment in microsomal steroidogenesis.

Adult↗
PubMed1983

A reexamination of pulsatile luteinizing hormone secretion in primary testicular failure.

The pulsatile pattern of LH secretion was studied in six patients with primary testicular failure and six healthy adult men by drawing peripheral blood samples every 10 min for 12 h. Mean basal LH concentrations were increased approximately 6-fold in hypogonadal men. In these patients mean absolute LH pulse amplitude was 3 times that of the controls [106 +/- 27 (SE) ng/ml vs. 31 +/- 2 ng/ml; P less than 0.01] and the frequency of spontaneous LH secretory episodes was increased 2-fold (between-pulse interval of 53 +/- 3 min vs. 107 +/- 8 min; P less than 0.01). Mean pulse amplitude was directly related to mean LH concentration in hypogonadal men (r = 0.94, P less than 0.01), but not in controls (r = 0.38, P = NS). Within each group there was no relationship between circulating testosterone or mean LH levels and LH pulse frequency. This study demonstrates that the increased circulating levels of LH in hypogonadal men are a consequence of an increase in both LH pulse frequency and pulse amplitude. The prolonged, more frequent sampling protocol used revealed a pattern of LH secretion not evident in previous studies. Finally, these data provide further, albeit indirect, evidence that androgens may regulate the intermittent release of LHRH in man.

Adult↗
PubMed1982

Studies of the human testis. XVI. Evaluation of multiple indexes of testicular function in relation to advanced age, idiopathic oligospermia, or varicocele.

Testicular function was evaluated by morphologic and biochemical methods in 11 infertile men with idiopathic oligospermia, 12 men with varicocele, and 14 elderly men. The results indicate the presence of two separate subgroups with idiopathic oligospermia with distinct endocrine and morphologic parameters and suggest the involvement of different pathogenetic factors for testicular disorders among these four groups. Biochemical indexes provide further confirmation of the validity of the Leydig cell cluster index (number of Leydig cell clusters per tubular section) as a useful evaluation guide. The results support the importance of combined studies of circulating hormones and testicular histologic features in providing insight into spermatogenic disorders. Recognition of etiologic diversity is an essential basis for further efforts to delineate and apply current or new hormonal techniques for therapy.

Adult↗
PubMed1982

The response of prolactin to chlorpromazine stimulation in men with hypogonadotrophic hypogonadism and early pubertal boys: relationship to sex steroid exposure.

The effect of chlorpromazine (CPZ) on prolactin (PRL) secretion was studied in fourteen sexually immature males; nine with idiopathic hypogonadotrophic hypogonadism and five who proved to be normal early pubertal boys. Initially, clinical features and basal levels of testosterone, LH and FSH in serum collected in the morning and the gonadotrophin responses to LHRH stimulation were similar in all subjects. Following CPZ the early pubertal boys increased PRL levels by at least 15 ng/ml, responses similar to those of normal men, whereas no subject with complete hypogonadotropism increased PRL by more than 5 ng/ml. Two subjects with incomplete hypogonadotropism ('fertile eunuchs') exhibited responses similar to normals. Treatment with human chorionic gonadotrophin (hCG) or testosterone enhanced the PRL response to CPZ in three of six hypogonadotrophic subjects. Ten additional hypogonadotrophic men studied while receiving long term treatment with hCG or testosterone also manifested normal responses to CPZ. These data indicate that lack of sex steroid exposure, rather than a more generalized hypothalamic disorder, explains the attenuated PRL response to CPZ found in untreated men with idiopathic hypogonadotrophic hypogonadism. Moreover, CPZ-stimulated PRL secretion may prove to be of practical value in distinguishing hypogonadotrophics from boys with delayed puberty.

Adolescent↗
PubMed1982

Episodic luteinizing hormone (LH) secretion and the response of LH and follicle-stimulating hormone to LH-releasing hormone in aged men: evidence for coexistent primary testicular insufficiency and an impairment in gonadotropin secretion.

The influence of aging on episodic LH secretion and the release of LH and FSH after LRH administration was studied in 14 healthy men, aged 65-80 yr. Mean morning serum testosterone levels were reduced by 16% (P less than 0.05) and serum LH and FSH concentrations were increased by nearly 2- and 3-fold, respectively (P less than 0.01), compared to levels in young men. LH secretory episodes were evident and did not differ significantly in either amplitude or frequency from those of young men in spite of the higher mean LH concentrations. The increments in serum LH and FSH levels after LRH and the areas under the response curves were similar in aged and young men. However, the time of the peak LH response was significantly delayed with aging (P less than 0.001), suggesting an alteration in the control of the releasable LH pool. Further, LH levels were slower to fall after the peak in elderly men (P less than 0.01), suggesting prolonged secretion of hormone after LRH stimulation. These changes did not relate to the basal hypersecretion of LH in elderly men, as the responses in young men with primary gonadal failure did not differ from those in healthy young men (P = NS). The possibility that increased LH molecular size leads to its reduced clearance was not supported by the similar Sephadex G-100 elution profiles for LH in both basal and post-LRH sera from young and old men. Our data indicate that Leydig cell function is impaired in healthy elderly men as a result of primary testicular insufficiency. These studies further reveal the presence of an additional hypothalamic-pituitary disorder of gonadotropin secretion associated with the aging process.

Adult↗
PubMed1982

Studies of the human testis. XVII. Gonadotropin regulation of intratesticular testosterone and estradiol in infertile men.

Serum levels of LH and FSH and the intratesticular concentrations of testosterone (T) and estradiol (E) were measured in biopsy tissue from 40 infertile men, aged 21-36 yr, of whom 21 were oligospermic men with varicocele and 19 were men with idiopathic oligospermia. Intratesticular T and E concentrations were negatively correlated (P less than 0.001) with testicular volumes, as measured with a calibrated orchidometer, suggesting that differences in measured intratesticular steroid levels in part reflect altered relative Leydig cell density as seminiferous tubular volume changes. To gather information about the regulation of intratesticular T and E by gonadotropins, we calculated an index of intratesticular steroid content by multiplying steroid concentration by testicular volume and compared these values with circulating LH and FSH levels. Highly significant positive correlations were found between both serum LH and FSH and intratesticular E content and between LH and FSH and intratesticular T content. Multivariant stepwise regression analysis revealed that while serum FSH is a strong predictor of intratesticular E (r = 0.72; P less than 0.001), serum LH is not (partial r = 0.00 when controlling for the influence of FSH). Instead, the apparent relationship between Serum LH and intratesticular E results from the highly positive correlation between serum LH and FSH in the patients studied (r = 0.71; P less than 0.001). Similarly, circulating LH levels are independently related to intratesticular T content (r = 0.67; P less than 0.001), whereas the relationship between FSH and T is indirect (partial r = 0.06 when controlling for the influence of LH). We believe that these associations suggest that the major regulator of intratesticular T content is LH and that FSH may be the important gonadotropin regulating intratesticular E.

Adult↗
PubMed1979

H-Y antigen mosaicism in the gonad of a 46,XX true hermaphrodite.

To clarify the mechanism for the coexistence of ovarian and testicular tissue in the 46,XX true hermaphrodite, we studied a 20-year-old phenotypic male with gynecomastia and elevated serum concentrations of estradiol in whom an ovotestis was discovered upon scrotal exploration. Y chromosomal material could not be detected by fluorescent Y-body analysis or Giemsa-banding technics in cells cultured from peripheral blood, breast or forearm skin or the ovarian or testicular portions of the ovotestis. However, serologic testing, using the sperm cytotoxicity assay, revealed that cells cultured from the testicular portion of the ovotestis were H-Y antigen positive whereas cells cultured from the ovarian portion were H-Y antigen negative. These observations indicate that the ovotestis arises from an H-Y+/H-Y- mosaic primordium.

Adult↗