EFFECTS OF ANDROGENS ON OVARIAN STRUCTURE AND FUNCTION

雄激素对雌性性分化的影响通常被认为是在病理学背景下（例如先天性肾上腺皮质增生导致的生殖器模糊），但在斑点鬣狗中，胎儿发育和性分化期间的高雄激素环境代表正常的生理学，而不是病理学。因此，斑点鬣狗代表了一个独特的系统，在其中研究产前雄激素对性分化的影响。在斑鬣狗中，子宫内的高雄激素暴露使雌性外生殖器雄性化到了极点，但雄激素对卵巢分化的影响还没有很好的研究。特别是，雄激素似乎增加卵泡闭锁的速度在发展中的卵巢，这可能解释了丰富的卵巢间质组织和相对缺乏的卵泡在斑点鬣狗。在拟议的研究中，我将研究一组雌性鬣狗，它们在子宫内时曾接触过抗雄激素。这些雌性动物现在是成年人，它们卵巢的结构和功能将与未治疗的对照组进行比较。将在体内和体外（单侧卵巢切除术后）评估卵巢对促性腺激素激发试验的类固醇生成反应性。卵巢切除术后，将测量卵泡数量和类固醇生成酶活性，并通过免疫细胞化学定量类固醇受体水平。这项研究将提高我们对产前暴露于雄激素如何影响卵巢结构和功能的理解。

Effects of androgens on female sexual differentiation are often considered within a pathological context (e.g. ambiguous genitalia resulting from congenital adrenal hyperplasia), but in the spotted hyena a high androgen milieu during fetal development and sexual differentiation represents normal physiology, not pathology. Thus, the spotted hyena represents a unique system in which to study the effects of antenatal androgens on sexual differentiation. High androgen exposure in utero masculinizes female external genitalia to the extreme in spotted hyenas, but the effects of androgens on ovarian differentiation are not well studied. Specifically, androgens appear to increase the rate of follicular atresia in the developing ovary, which may explain the abundance of ovarian interstitial tissue and relative paucity of follicles in spotted hyenas. In the proposed research I will study a group of female hyenas that were previously exposed to anti-androgens while in utero. These females are now adults and the structure and function of their ovaries will be compared to that of untreated controls. The steroidogenic responsiveness of the ovaries to a gonadotropin challenge test will be assessed in vivo, as well as in vitro (after unilateral oophorectomy). Following oophorectomy, follicle number and steroidogenic enzyme activity will be measured, and steroid receptor levels will be quantified by immunocytochemistry. This research will improve our understanding of how prenatal exposure to androgens affects ovarian structure and function.