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.

Regulation of rat pituitary gonadotropin-releasing hormone receptor mRNA levels in vivo and in vitro.

Abstract: The recent isolation of cDNAs encoding the rat pituitary gonadotropin-releasing hormone receptor (GnRHR) allows studies of the regulation of the synthesis of the GnRHR and its relationship to reproductive function. Analyses of the regulation of GnRHR mRNA levels in the rat pituitary in vivo revealed a progressive increase in levels to 2.0 +/- 0.2-fold after ovariectomy (OVX) and 5.2 +/- 1.3-fold after castration (CAST) (21 days post-operative), compared to intact adult female and male controls, respectively. Replacement therapy with 17 beta-estradiol benzoate in 21-day post-OVX female rats resulted in a marked decrease in GnRHR mRNA levels by 7 days, compared to controls. In contrast, therapy with testosterone propionate in 21-day post-CAST male rats resulted in only a modest decrease in GnRHR mRNA levels. Thus, manipulation of the reproductive endocrine system in vivo results in alterations in GnRHR synthesis at the pretranslational level, which parallel known changes in cell surface gonadotropin-releasing hormone (GnRH) binding activities. The treatment of superfused primary monolayer cultures of rat pituitary cells with hourly pulses of GnRH (10 nM, 6 min/h) resulted in a marked increase in GnRHR mRNA levels (12.8 +/- 4.3-fold compared to untreated cells). In contrast, treatment of cultured cells with continuous GnRH caused no change in GnRHR mRNA levels. These in vitro data show homologous regulation of GnRHR gene expression by GnRH, and suggest that the changes in GnRHR gene expression observed in vivo may be attributable at least in part to changes in the pattern of hypothalamic GnRH secretion.

Androgen replacement therapy in male patients with rheumatoid arthritis.

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

Effect of bipolar androgen therapy for asymptomatic men with castration-resistant prostate cancer: Results from a pilot clinical study

Abstract: Targeting androgen receptor (AR) axis signaling by disrupting androgen-AR interactions remains the primary treatment for metastatic prostate cancer. Unfortunately, all men develop resistance to primary castrating therapy and secondary androgen deprivation therapies (ADTs). Resistance develops in part because castration-resistant prostate cancer (CRPC) cells adaptively up-regulate AR levels through overexpression, amplification, and expression of ligand-independent variants in response to chronic exposure to a low-testosterone environment. However, preclinical models suggest that AR overexpression represents a therapeutic liability that can be exploited via exposure to supraphysiologic testosterone to promote CRPC cell death. Preclinical data supported a pilot study in which 16 asymptomatic CRPC patients with low to moderate metastatic burden were treated with testosterone cypionate (400 mg intramuscular; day 1 of 28) and etoposide (100 mg oral daily; days 1 to 14 of 28). After three cycles, those with a declining prostate-specific antigen (PSA) continued on intermittent testosterone therapy monotherapy. Castrating therapy was continued to suppress endogenous testosterone production, allowing for rapid cycling from supraphysiologic to near-castrate serum testosterone levels, a strategy termed bipolar androgen therapy (BAT). BAT was well tolerated and resulted in high rates of PSA (7 of 14 evaluable patients) and radiographic responses (5 of 10 evaluable patients). Although all men showed eventual PSA progression, four men remained on BAT for ≥1 year. All patients (10 of 10) demonstrated PSA reductions upon receiving androgen-ablative therapies after BAT, suggesting that BAT may also restore sensitivity to ADTs. BAT shows promise as treatment for CRPC and should be further evaluated in larger trials.

Elevated 17β-estradiol protects females from influenza A virus pathogenesis by suppressing inflammatory responses.

Abstract: Studies of the 1918 H1N1 influenza pandemic, the H5N1 avian influenza outbreak, and the 2009 H1N1 pandemic illustrate that sex and pregnancy contribute to severe outcome from infection, suggesting a role for sex steroids. To test the hypothesis that the sexes respond differently to influenza, the pathogenesis of influenza A virus infection was investigated in adult male and female C57BL/6 mice. Influenza infection reduced reproductive function in females and resulted in greater body mass loss, hypothermia, and mortality in females than males. Whereas lung virus titers were similar between the sexes, females had higher induction of proinflammatory cytokines and chemokines, including TNF-α, IFN-γ, IL-6, and CCL2, in their lungs than males. Removal of the gonads in both sexes eliminated the sex difference in influenza pathogenesis. Manipulation of testosterone or dihydrotestosterone concentrations in males did not significantly impact virus pathogenesis. Conversely, females administered high doses of estradiol had a ≥10-fold lower induction of TNF-α and CCL2 in the lungs and increased rates of survival as compared with females that had either low or no estradiol. The protective effects of estradiol on proinflammatory cytokines and chemokines, morbidity, and mortality were primarily mediated by signaling through estrogen receptor α (ERα). In summary, females suffer a worse outcome from influenza A virus infection than males, which can be reversed by administration of high doses of estradiol to females and reflects differences in the induction of proinflammatory responses and not in virus load.