Lee G Y, Croop J M, Anderson E
Department of Cell Biology, Children's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Biol Reprod. 1998 Feb;58(2):330-7. doi: 10.1095/biolreprod58.2.330.
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.
通过每日注射脱氢表雄酮（DHEA）可在青春期前大鼠中诱导多囊卵巢（PCO）形成。在经DHEA处理的大鼠卵巢囊液中存在高水平的孕酮、雄激素和雌激素。本研究的目的是调查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C219（一种识别170 kDa ATP依赖性跨膜泵的单克隆抗体），我们将Pgp定位在囊性卵泡颗粒细胞膜上，而不是卵母细胞或卵泡膜/间质细胞膜上。在正常青春期前大鼠中，Pgp定位于排卵前卵泡产生孕酮的颗粒细胞以及eCG/hCG刺激后的黄体细胞中，但在生长卵泡、卵母细胞或卵泡膜/间质细胞中未检测到。对这些组织的Northern分析表明，Pgp mRNA在排卵前卵泡、囊性卵泡和黄体中强烈表达。从这些发现来看，颗粒细胞产生的孕酮可能以自分泌方式作用以诱导Pgp的表达。孕酮可能与这些颗粒细胞的Pgp相互作用以调节类固醇流出。
