5alpha-Androstane-3beta,17beta-diol (3beta-diol), an estrogenic metabolite of 5alpha-dihydrotestosterone, is a potent modulator of estrogen receptor ERbeta expression in the ventral prostrate of adult rats.
5alpha-Androstane-3beta,17beta-diol (3beta-diol), an estrogenic metabolite of 5alpha-dihydrotestosterone, is a potent modulator of estrogen receptor ERbeta expression in the ventral prostrate of adult rats.
复制标题
5alpha-Androstane-3beta,17beta-diol (3beta-diol) 是 5α-二氢睾酮的雌激素代谢物，是成年大鼠腹侧前列腺中雌激素受体 ERbeta 表达的有效调节剂。
作者：
A. Oliveira;P. H. Coelho;F. Guedes;G. A. Mahecha;R. Hess;Cleida A Oliveira
前列腺是二氢睾酮 (DHT) 的主要靶标之一，但该腺体也被认为是雌激素的非经典靶标，因为它表达两种类型的雌激素受体 (ER)，尤其是 ERbeta。然而，前列腺中芳香酶和雌二醇的浓度较低，表明雌二醇可能不是唯一在前列腺中发挥作用的雌激素分子。众所周知，DHT 可代谢为 5α-雄甾烷-3β,17β-二醇（3β-二醇），这是一种与 ERbeta 结合但不与 AR 结合的激素。前列腺中3β-二醇的浓度远高于雌二醇。基于高浓度的 3β-二醇，并且由于该代谢物是生理 ERbeta 配体，我们假设 3β-二醇可能参与 ERbeta 表达的调节。为了检验这一假设，对成年雄性大鼠进行去势，然后用雌二醇、DHT 或 3β-二醇替代。通过免疫组织化学和蛋白质印迹分析研究前列腺中的 ERbeta 和 AR 蛋白水平。结果显示，去势后，前列腺结构发生显着变化，ERbeta和AR蛋白水平下降。雌二醇对分析参数的影响很小。 DHT 诱导 ERbeta 部分恢复，同时它是 AR 表达最有效的诱导剂。用 3β-二醇替代可诱导最高水平的 ERbeta，但在恢复 AR 表达和腺体结构方面效果相对较差。这些结果证明，3β-二醇在前列腺中的功能之一可能是对其天然受体 ERbeta 的自动调节。
Prostate is one of the major targets for dihydrotestosterone (DHT), however this gland is also recognized as a nonclassical target for estrogen as it expresses both types of estrogen receptors (ER), especially ERbeta. Nevertheless, the concentrations of aromatase and estradiol in the prostate are low, indicating that estradiol may not be the only estrogenic molecule to play a role in the prostate. It is known that DHT can be metabolized to 5alpha-androstane-3beta,17beta-diol (3beta-diol), a hormone that binds to ERbeta but not to AR. The concentration of 3beta-diol in prostate is much higher than that of estradiol. Based on the high concentration of 3beta-diol and since this metabolite is a physiological ERbeta ligand, we hypothesized that 3beta-diol would be involved in the regulation of ERbeta expression. To test this hypothesis, adult male rats were submitted to castration followed by estradiol, DHT or 3beta-diol replacement. ERbeta and AR protein levels in the prostate were investigated by immunohistochemistry and Western blotting assays. The results showed that after castration, the structure of the prostate was dramatically changed and ERbeta and AR protein levels were decreased. Estradiol had just minor effects on the parameters analyzed. DHT-induced partial recovery of ERbeta while it was the most effective inductor of AR expression. Replacement with 3beta-diol-induced the highest levels of ERbeta, but was comparatively less effective in recovering the AR expression and the gland structure. These results offer evidence that one functional role of 3beta-diol in the prostate may be autoregulation of its natural receptor, ERbeta.