hCG-Induced Down-Regulation of PPARγ and Liver X Receptors Promotes Periovulatory Progesterone Synthesis by Macaque Granulosa Cells
hCG-Induced Down-Regulation of PPARγ and Liver X Receptors Promotes Periovulatory Progesterone Synthesis by Macaque Granulosa Cells
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DOI：
10.1210/en.2010-0698
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发表时间：
2010-12-01
期刊：
影响因子：
4.8
通讯作者：
Chaffin, Charles L.
中科院分区：
文献类型：
--
作者：
Puttabyatappa, Muraly;VandeVoort, Catharine A.;Chaffin, Charles L.
排卵刺激诱导了灵长类动物卵泡中黄体酮合成的快速和急剧增加。然而，对于导致从雌激素到黄体酮产生转变的早期事件知之甚少。由于甾体生成代表了胆固醇代谢的一个方面，因此有人假设，调节胆固醇平衡的转录因子可能是最早响应排卵刺激而发生变化的转录因子之一。在人绒毛膜促性腺激素（hCG）排卵前或24小时后，通过控制卵巢刺激方案从恒河猴卵泡中分离出颗粒细胞。过氧化物酶体增殖体激活受体- γ (PPARG)和肝脏X受体[核受体（NR）1H2， NR1H3]在hCG后3小时内下降，逆向胆固醇转运体atp结合盒（ABC）A1和ABCG1也是如此。在促排卵前用hCG和罗格列酮处理分离的颗粒细胞导致NR1H3和ABCG1增加，类固醇急性调节（STAR）蛋白和清除率受体- bi （SCARB1）降低。一种肝X受体激动剂能减弱hcg诱导的体外孕酮合成，增加ABCA1和ABCG1的表达，抑制STAR、P450侧链切割A1、羟基类固醇脱氢酶3B和SCARB1。这些数据表明，LH/CG对灵长类动物排卵前卵泡的初始作用是迅速降低PPARG的表达，导致NR1H3的减少，从而将平衡从通过ABCA1和ABCG1的胆固醇外排转移到胆固醇摄取（SCARB1）和代谢（STAR， P450侧链切割A1，羟基类固醇脱氢酶3B）。PPARG和肝脏X受体的调控发生在3小时内，这强烈表明灵长类动物黄体生成素卵泡的早期事件对成功排卵和黄体形成至关重要。中华内分泌学杂志(5):582 - 582；
An ovulatory stimulus induces the rapid and dramatic increase in progesterone synthesis by the primate ovarian follicle. However, little is known about the early events leading to the shift from estrogen to progesterone production. Because steroidogenesis represents an aspect of cholesterol metabolism, it was hypothesized that transcription factors regulating cholesterol balance would be among the earliest to change in response to an ovulatory stimulus. Granulosa cells were isolated from rhesus monkey follicles following controlled ovarian stimulation protocols before or up to 24 hr after an ovulatory human chorionic gonadotropin (hCG) bolus. The peroxisome proliferator-activated receptor-gamma (PPARG) and the liver X receptors [nuclear receptor (NR)1H2, NR1H3] decreased within 3 hr of hCG, as did the reverse cholesterol transporters ATP-binding cassette (ABC)A1 and ABCG1. Treatment of granulosa cells isolated before an ovulatory stimulus with hCG and rosiglitizone resulted in an increase in NR1H3 and ABCG1, and decreased steroidogenic acute regulatory (STAR) protein and scavenger receptor-BI (SCARB1). A liver X receptor agonist attenuated hCG-induced progesterone synthesis in vitro and increased the expression of ABCA1 and ABCG1, and suppressed STAR, P450 side-chain cleavage A1, hydroxysteroid dehydrogenase 3B, and SCARB1. These data suggest that an initial action of LH/CG on the primate preovulatory follicle is to rapidly reduce the expression of PPARG, resulting in reduced NR1H3 with the consequence shifting the balance from cholesterol efflux via ABCA1 and ABCG1 to cholesterol uptake (SCARB1) and metabolism (STAR, P450 side-chain cleavage A1, hydroxysteroid dehydrogenase 3B). That the regulation of PPARG and the liver X receptors occurs within 3 hr strongly indicates that early events in the primate luteinizing follicle are critical to successful ovulation and luteal formation. (Endocrinology 151: 5865-5872,