Testosterone

About: Testosterone is a research topic. Over the lifetime, 23258 publications have been published within this topic receiving 808079 citations. The topic is also known as: 4-androsten-17beta-ol-3-one & 4-Androsten-3-one-17b-ol.

Molecular genetics and pathophysiology of 17 beta-hydroxysteroid dehydrogenase 3 deficiency.

Abstract: Autosomal recessive mutations in the 17 beta-hydroxysteroid dehydrogenase 3 gene impair the formation of testosterone in the fetal testis and give rise to genetic males with female external genitalia. Such individuals are usually raised as females, but virilize at the time of expected puberty as the result of increases in serum testosterone. Here we describe mutations in 12 additional subjects/families with this disorder. The 14 mutations characterized to date include 10 missense mutations, 3 splice junction abnormalities, and 1 small deletion that results in a frame shift. Three of these mutations have occurred in more than 1 family. Complementary DNAs incorporating 9 of the 10 missense mutations have been constructed and expressed in reporter cells; 8 of the 9 missense mutations cause almost complete loss of enzymatic activity. In 2 subjects with loss of function, missense mutations testosterone levels in testicular venous blood were very low. Considered together, these findings strongly suggest that the common mechanism for testosterone formation in postpubertal subjects with this disorder is the conversion of circulating androstenedione to testosterone by one or more of the unaffected 17 beta-hydroxysteroid dehydrogenase isoenzymes.

The effects of androgens on the regulation of lipolysis in adipose precursor cells.

Abstract: Adipose precursor cells from male rats were exposed in primary culture to testosterone (T) or dihydrotestosterone (DHT), and their effects on the regulation of lipolysis were studied. T, but not DHT, stimulated catecholamine-induced lipolysis in a dose-dependent manner, including physiological concentrations. The effect was equally pronounced with isoproterenol (a pure beta-adrenergic agonist) and norepinephrine (a mixed alpha 2- and beta-adrenergic agonist). The higher lipolytic capacity of catecholamines on T-treated cells was paralleled by a similar increase in the number of beta-adrenoceptors in the cells, without a change in the receptor affinity, suggesting that T induced new synthesis or externalization of beta-adrenoceptors. Both T and DHT stimulated forskolin-induced lipolysis, suggesting an androgen effect at the level of the catalytic subunit of adenylate cyclase. The pertussis toxin-stimulated lipolysis was not influenced by the presence of androgens in the culture medium, and no effect was seen on the antilipolytic effect of insulin. These effects did not disappear in the presence of an aromatase inhibitor, suggesting that the T effects were not mediated by conversion to estrogens. These cells showed specific saturable binding for androgens, with a Kd in the range of androgen concentrations shown to be active. In conclusion, androgens enhance the lipolytic capacity of these cells by increasing the apparent number of beta-adrenoceptors (T only) and the activity of adenylate cyclase (both T and DHT). These changes are not mediated by conversion to estrogens. These effects probably occur via binding to specific androgen receptors.

Increased prostate cell proliferation and loss of cell differentiation in mice lacking prostate epithelial androgen receptor.

Abstract: Developmental studies of the prostate have established that ductal morphogenesis, epithelial cytodifferentiation, and proliferation/apoptosis are regulated by androgens acting through stromal androgen receptor (AR). Here, we found mice lacking epithelial AR within the mature prostate (pes-ARKO) developed prostate tissue that was less differentiated and hyperproliferative relative to WT littermates. Epithelial AR protein was significantly decreased in 6-week-old mice and was nearly absent by >/=24 weeks of age. Circulating levels of testosterone, external genitalia, or fertility were not altered in pes-ARKO mice. A significant (P < 0.05) increase in bromo-deoxyuridine-positive epithelia was observed in ventral and dorsal-lateral prostates of pes-ARKO mice at 24 weeks of age. Less differentiation was observed as indicated by decreased epithelial height and glandular infolding through 24 weeks of age, differentiation markers probasin, PSP-94, and Nkx3.1 were sig nificantly decreased, and epithelial sloughing and luminal cell apoptosis increased from 6 to 32 weeks of age in pes-ARKO mice. Gain of function occurred by crossing pes-ARKO to the T857A transgenic mice containing constitutively activated AR. In T857A-pes-ARKO mice prostates were of normal size, contained glandular infoldings, and maintained high secretory epithelium, and the appropriate prostatic epithelial proliferation was restored. Collectively, these results suggest that prostatic epithelial AR plays an important role in the homeostasis of the prostate gland. These data support the hypothesis that epithelial AR controls prostate growth by suppressing epithelial proliferation in the mature gland.