McGinnis M Y, Dreifuss R M
Department of Anatomy, Mount Sinai School of Medicine, City University of New York, New York 10029.
Endocrinology. 1989 Feb;124(2):618-26. doi: 10.1210/endo-124-2-618.
The purpose of this study was 2-fold: 1) to use gonadal steroid hormone exposures in the physiological range to assess the relative roles of testosterone (T), estradiol (E2), and dihydrotestosterone (DHT) in the expression of male sexual behavior, and 2) to determine whether androgen receptor (AR) or estrogen receptor (E2R) occupation is increased after exposure to these various gonadal steroid hormones. Sexually experienced, castrated male rats implanted sc with Silastic capsules containing T, 10% E2, DHT, 10% E2 plus DHT, or blanks provided hormone levels in the physiological range. Copulatory behavior was measured on days 2-4, 5-7, 10-12, and 14-16 of steroid treatment. Although T, E2, and E2 plus DHT treatments all activated mounting, only T was effective in restoring ejaculation in 100% of the males. DHT alone had no effect on any aspect of male sexual behavior. Brains of males given these various hormone treatments were assayed for both cell nuclear AR and cell nuclear E2R binding in the hypothalamus, preoptic area, amygdala, and septum. Results indicate that when hormone levels in the physiological range were employed, T and DHT bind primarily to AR, whereas E2 binds to E2R. In a second experiment, 0.5% E2 plus DHT was found to yield AR and E2R levels comparable to those in rats receiving T capsules. Male rats bearing these capsules showed virtually no sexual behavior, demonstrating that elevation of AR and E2R levels comparable to those generated by T is not sufficient to induce male sexual behavior. We then measured intact AR and E2R levels and determined that in intact males E2R levels were higher than in T-treated males. These E2R levels could be replicated using 1.0% E2. Males exposed to 1.0% E2 plus DHT failed to display male sexual behavior. These data suggest that 1) relatively high and prolonged levels of E2R occupation are required for estrogen activation of male sexual behavior, 2) high levels of AR occupation induced by DHT are not sufficient to activate male sexual behavior, and 3) in intact male rats T, acting via androgen receptors, plays a primary role in mediating the expression of masculine sexual behavior.
1）利用生理范围内的性腺类固醇激素暴露来评估睾酮（T）、雌二醇（E2）和双氢睾酮（DHT）在雄性性行为表达中的相对作用；2）确定暴露于这些不同的性腺类固醇激素后，雄激素受体（AR）或雌激素受体（E2R）的占有率是否增加。有性经验的去势雄性大鼠皮下植入含有T、10% E2、DHT、10% E2加DHT或空白的硅橡胶胶囊，以提供生理范围内的激素水平。在类固醇治疗的第2 - 4天、5 - 7天、10 - 12天和14 - 16天测量交配行为。虽然T、E2以及E2加DHT处理均能激活爬跨行为，但只有T能使100%的雄性恢复射精。单独使用DHT对雄性性行为的任何方面均无影响。对接受这些不同激素处理的雄性大鼠的大脑进行检测，以测定下丘脑、视前区、杏仁核和隔区的细胞核AR和细胞核E2R结合情况。结果表明，当采用生理范围内的激素水平时，T和DHT主要与AR结合，而E2与E2R结合。在第二个实验中，发现0.5% E2加DHT产生的AR和E2R水平与接受T胶囊的大鼠相当。携带这些胶囊的雄性大鼠几乎没有性行为，这表明与T产生的水平相当的AR和E2R水平升高不足以诱导雄性性行为。然后我们测量了完整的AR和E2R水平，并确定在完整雄性大鼠中E2R水平高于接受T处理的雄性大鼠。使用1.0% E2可复制这些E2R水平。暴露于1.0% E2加DHT的雄性大鼠未表现出雄性性行为。这些数据表明：1）雌激素激活雄性性行为需要相对较高且持续的E2R占有率；2）DHT诱导的高水平AR占有率不足以激活雄性性行为；3）在完整雄性大鼠中，T通过雄激素受体发挥作用，在介导雄性性行为表达中起主要作用。
