Progesterone regulation of the expression and function of multidrug resistance type I in porcine granulosa cells

Abstract: P-glycoprotein (P-gp) coded with the multidrug resistance type I (MDR1) is expressed in various normal tissues including ovaries and may function as detoxification and steroid transport. The present study was performed to analyze the expression and function of MDR1 in granulosa cells stimulated with FSH, LH, estradiol-17β (E) and progesterone (P). The granulosa cells isolated from porcine ovarian follicles were cultured for 24h in a serum-supplemented medium, and then cultured for 48h with the hormones in a serum-free culture medium. MDR1 was highly expressed in large follicles and induced in cultured granulosa cells stimulated with LH as revealed by RT-PCR. Highly expressed MDR1 resulted in the increased P-gp activity. However, FSH had no effect. P significantly increased the MDR1 expression and P-gp activity in the cells stimulated with LH, whereas E had no stimulatory effect. Aminoglutethimide suppressed the MDR1 expression and P-gp activity, but which were completely restored by P. These results indicate that P participates in MDR1 expression and P-gp function of granulosa cells. [Copyright &y& Elsevier]