Progesterone-dependent and -independent expression of the multidrug resistance type I gene in porcine granulosa cells.

A primary role of plasma membrane P-glycoprotein (P-gp), encoded by multidrug resistance type I (MDR1), is to protect against naturally occurring xenotoxics. Progesterone (P(4)) profoundly influences MDR1 expression in granulosa cells and luteal cells. Here, P(4) regulation of MDR1 expression was investigated in porcine granulosa cells using the P(4)-mediated promoter activity assay and a P4 receptor (PR) antagonist (RU-486). The promoter activity was measured chronologically for 48 h in cells transfected with the PR response element-containing pGL3. LH could stimulate the promoter activity through endogenous P4, with a maximum activity at 5 h. MDR1 mRNA level was highly maintained at 24-36 h. Conversely, exogenous P4 prolonged the promoter activity to further 10 h, and the high level of MDR1 mRNA was maintained even at 48 h. RU-486 completely inhibited the promoter activity, but the level of MDR1 mRNA rapidly increased in the presence of RU-486. The granulosa cells may become susceptible to RU-486 as a xenotoxic to rapidly express MDR1 for protection against it. These results indicate that MDR1 is expressed in porcine granulosa cells through P4-dependent and -independent regulations.