Multidrug resistance gene expression correlates with progesterone production in dehydroepiandrosterone-induced polycystic and equine chorionic gonadotropin-stimulated ovaries of prepubertal rats
Multidrug resistance gene expression correlates with progesterone production in dehydroepiandrosterone-induced polycystic and equine chorionic gonadotropin-stimulated ovaries of prepubertal rats
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DOI：
10.1095/biolreprod58.2.330
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发表时间：
1998-02-01
影响因子：
3.6
通讯作者：
Anderson, E
中科院分区：
文献类型：
--
作者：
Lee, GY;Croop, JM;Anderson, E
每日注射脱氢表雄酮（DHEA）可诱导青春期前大鼠发生多囊卵巢（PCO）。在脱氢表雄酮处理的大鼠卵巢的囊液中有高水平的孕酮、雄激素和雌激素。本研究的目的是探讨PCO中高水平的类固醇是否与多药耐药基因产物P-糖蛋白（Pgp）的表达相关。使用识别170-kDa ATP依赖性跨膜泵的单克隆抗体C219，我们将Pgp定位于囊性卵泡中颗粒细胞的质膜上，而不是卵母细胞或卵泡膜/间质细胞的质膜上。在正常青春期前大鼠中，Pgp定位于排卵前卵泡的产生孕酮的颗粒细胞和hCG/hCG刺激后的黄体细胞中，而不是生长卵泡中，卵母细胞或卵泡膜/间质细胞。这些组织的北方分析表明，排卵前卵泡，囊性卵泡和黄体中的Pgp mRNA的强表达。从这些发现看来，颗粒细胞产生的孕酮可能以自分泌的方式诱导Pgp的表达。这可能是可能的，孕酮与这些颗粒细胞的Pgp相互作用，以调节类固醇外流。
Polycystic ovaries (PCO) can be induced in prepubertal rats by daily injection of dehydroepiandrosterone (DHEA). There are high levels of progesterone, androgens, and estrogens in the cystic fluid of DHEA-treated rat ovaries. The purpose of this study was to investigate whether high levels of steroids in the PCO correlate with the expression of multidrug resistance gene product P-glycoprotein (Pgp). Using C219, a monoclonal antibody that recognizes the 170-kDa ATP-dependent transmembrane pump, we localized Pgp on the plasma membrane of granulosa cells in cystic follicles but not of oocytes or thecal/interstitial cells, in normal prepubertal rats, Pgp was localized in progesterone-producing granulosa cells of the preovulatory follicles and in cells of the corpora lutea after eCG/hCG stimulation, but not in growing follicles, oocytes, or thecal/interstitial cells. Northern analysis of these tissues indicated strong expression of Pgp mRNA in the preovulatory follicles, cystic follicles, and corpora lutea. From these findings it seems that progesterone produced by the granulosa cells may act in an autocrine manner to induce the expression of Pgp. It may be possible that progesterone interacts with the Pgp of these granulosa cells to modulate steroid efflux.