Roselli C E, Resko J A
Endocrinology. 1984 Jun;114(6):2183-9. doi: 10.1210/endo-114-6-2183.
We studied the regulation of aromatase activity in the hypothalamus-preoptic area ( HPOA ) of adult male rats using a sensitive in vitro assay which measures the amount of 3H2O formed by tissue homogenates during the conversion of [1 beta-3H]androstenedione to estrone. After castration, HPOA aromatase activity was decreased by 60% (P less than 0.05), seminal vesicle (SV) and ventral prostate (VP) weights were significantly decreased (P less than 0.05), and serum LH levels were elevated. We found that testosterone (T) or 5 alpha-dihydrotestosterone (DHT) administered in Silastic capsules for 7 days reversed the effects of castration. Testosterone and DHT stimulated HPOA aromatase activity 133% and 92%, respectively (P less than 0.05). Both steroids significantly increased SV and VP wet weights and suppressed serum levels of LH (P less than 0.05). Administration of either estradiol or progesterone did not reverse the effect of castration on HPOA aromatase activity or any other parameter measured. To determine the involvement of androgen receptors in the mechanism by which androgens affect brain aromatase, we administered the nonsteroidal antiandrogen flutamide to intact male rats (15 mg/day for 7 days). There was 42% less HPOA aromatase activity in treated rats than in oil-injected controls (P less than 0.05). Flutamide significantly decreased SV and VP wet weights, while serum LH levels were enhanced (P less than 0.05). Likewise, administration of flutamide to T-implanted castrated males blocked the T-induced increase in HPOA aromatase activity and accessory sexual organ wet weights, and prevented the T-induced suppression of serum LH. Flutamide given alone to castrated rats had no effect. Since both T and DHT stimulated HPOA aromatase activity and since the effects of T are blocked by the concomitant administration of the antiandrogen flutamide, we concluded that the control of HPOA aromatase activity by androgens is receptor mediated.
我们使用一种灵敏的体外测定法，研究成年雄性大鼠下丘脑 - 视前区（HPOA）中芳香化酶活性的调节，该测定法可测量组织匀浆在将[1β - 3H]雄烯二酮转化为雌酮过程中形成的3H2O的量。去势后，HPOA芳香化酶活性降低了60%（P < 0.05），精囊（SV）和腹侧前列腺（VP）重量显著降低（P < 0.05），血清促黄体生成素（LH）水平升高。我们发现，用硅橡胶胶囊给药7天的睾酮（T）或5α - 双氢睾酮（DHT）可逆转去势的影响。睾酮和DHT分别刺激HPOA芳香化酶活性133%和92%（P < 0.05）。两种类固醇均显著增加SV和VP湿重，并抑制血清LH水平（P < 0.05）。给予雌二醇或孕酮均不能逆转去势对HPOA芳香化酶活性或所测任何其他参数的影响。为了确定雄激素受体在雄激素影响脑芳香化酶机制中的作用，我们给完整雄性大鼠施用非甾体抗雄激素氟他胺（15毫克/天，共7天）。与注射油的对照组相比，处理组大鼠的HPOA芳香化酶活性降低了42%（P < 0.05）。氟他胺显著降低SV和VP湿重，同时血清LH水平升高（P < 0.05）。同样，给植入T的去势雄性大鼠施用氟他胺可阻断T诱导的HPOA芳香化酶活性增加和附属性腺湿重增加，并阻止T诱导的血清LH抑制。单独给去势大鼠施用氟他胺没有效果。由于T和DHT均刺激HPOA芳香化酶活性，且T的作用可被同时施用的抗雄激素氟他胺阻断，我们得出结论，雄激素对HPOA芳香化酶活性的控制是受体介导的。
