Synthetic antiprogestins stimulate human granulosa cell estradiol production in vitro

The effect of synthetic antiprogestins, RMI 14156 and STS 557, on gonadotrophin stimulated estradiol (E2) production in human ovarian granulosa cells (GC) has been tested in vitro, to see if by virtue of their antiprogestational activity these compounds would promote the production of E2, and thereby follicular growth. Granulosa cells from human ovaries were cultured in modified minimum essential medium with or without luteinising hormone (LH, 10 ng/ml), follicle stimulating hormone (FSH, 100 ng/ml), androstenedione (A, 10(-7) M), RMI 14156 (10(-9) M-10(-5) M) and STS 557 (10(-9) M-10(-5) M), in a humidified 95% air 5% CO2 atmosphere at 37 degrees C for 48 hours. RMI 14156 and STS 557 were found to stimulate the production of E2 by cultured human GC in a dose dependent manner, the stimulation being significant (P less than 0.001-P less than 0.05) at higher doses (10(-6) M, 10(-5) M). The two antiprogestins used also stimulated the gonadotrophin induced E2 production significantly. Results demonstrated that these synthetic antiprogestins, having an 'estra' type of basic structure RMI 14156 17 beta hydroxy-7 alpha-methyl-5-estra-en-3-one); STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4,9(10)diene-3-one) can directly promote E2 production from human ovarian GC in vitro.