Multidrug resistance gene expression correlates with progesterone production in dehydroepiandrosterone-induced polycystic and equine chorionic gonadotropin-stimulated ovaries of prepubertal rats

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.