Effects of Sex Steroids on the Spinal Gastrin-Releasing Peptide System Controlling Male Sexual Function in Rats
Effects of Sex Steroids on the Spinal Gastrin-Releasing Peptide System Controlling Male Sexual Function in Rats
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DOI：
10.1210/en.2018-00043
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发表时间：
2018-04-01
期刊：
影响因子：
4.8
通讯作者：
Sakamoto, Hirotaka
中科院分区：
文献类型：
--
作者：
Oti, Takumi;Takanami, Keiko;Sakamoto, Hirotaka
腰骶脊髓胃泌素释放肽（GRP）系统控制雄性大鼠性功能。相比之下，雌性大鼠在青春期前后几乎检测不到GRP神经元，此时卵巢循环中的类固醇激素（如雌二醇和黄体酮）水平正在增加。然而，关于卵巢类固醇对女性青春期和成年期中枢神经系统的女性化或男性化作用的信息很少。在本研究中，为了可视化体内脊髓GRP神经元，我们建立了GRP启动子-金星转基因（Tg）大鼠系，通过金星荧光检测研究了性类固醇激素对大鼠腰椎GRP表达的影响。在这些Tg大鼠中，控制雄性性功能的雌雄二型脊髓GRP神经元被金星荧光清晰地标记。正如预期的那样，雄性脊髓的金星荧光在去势后明显下降，并通过慢性雄激素替代恢复。此外，雄激素诱导的金星在成年Tg雄性脊髓中的表达在黄体酮的慢性治疗中显著减弱，而雌二醇则没有。使用人GRP启动子构建的荧光素酶测定显示，雄激素增强了脊髓GRP系统，更引人注目的是，黄体酮通过雄激素受体介导的机制抑制了GRP系统。这些结果表明，循环雄激素可能在大鼠乃至人类的脊髓GRP系统控制男性性功能中发挥重要作用，黄体酮可能是女性青春期发育过程中脊髓GRP系统中一个重要的雌性化因子。
The gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord controls male sexual function in rats. In contrast, in female rats, GRP neurons could scarcely be detected around puberty when circulating ovarian steroid hormones such as estradiol and progesterone levels are increasing. However, little information is available on feminizing or demasculinizing effects of ovarian steroids on the central nervous system in female puberty and adulthood. In this study, to visualize the spinal GRP neurons in vivo, we generated a GRP-promoter-Venus transgenic (Tg) rat line and studied the effects of the sex steroid hormones on GRP expression in the rat lumbar cord by examining the Venus fluorescence. In these Tg rats, the sexually dimorphic spinal GRP neurons controlling male sexual function were clearly labeled with Venus fluorescence. As expected, Venus fluorescence in the male lumbar cord was markedly decreased after castration and restored by chronic androgen replacement. Furthermore, androgen-induced Venus expression in the spinal cord of adult Tg males was significantly attenuated by chronic treatment with progesterone but not with estradiol. A luciferase assay using a human GRP-promoter construct showed that androgens enhance the spinal GRP system, and more strikingly, that progesterone acts to inhibit the GRP system via an androgen receptor-mediated mechanism. These results demonstrate that circulating androgens may play an important role in the spinal GRP system controlling male sexual function not only in rats but also in humans and that progesterone could be an important feminizing factor in the spinal GRP system in females during pubertal development.