Interaction of prostaglandin F-2 alpha and gonadotropin-releasing hormone on progesterone and estradiol production in human granulosa-luteal cells

This study examined the effects of prostaglandin-F-2 alpha (PGF(2 alpha)), GnRH, and their interactions on steroidogenesis in human granulosa-luteal cells (GLCs). Human GLCs collected from in vitro fertilization patients were cultured for one or eight days, followed by a 24-h treatment period, after which media were collected and radioimmunoassayed for progesterone and estradiol. In the first experiment, GLCs were treated with vehicle, PCF2 alpha (10(-9) M), GnRH (10(-6) M), or PGF(2 alpha) plus GnRH, with or without hCG (1 IU/ml). Neither PGF(2 alpha) nor GnRH alone had a significant effect; however, the combination of PGF(2 alpha) plus GnRH significantly stimulated steroidogenesis. Similarly, co-application enhanced the luteolytic effects of PGF(2 alpha). In a second experiment, PGF(2 alpha) and GnRH concentration-response curves were crossed into a matrix of 49 separate treatments. Responses were plotted in three-dimensions and as two-dimensional ''slices'' that were analyzed statistically. In the presence of high concentrations of GnRH (10-6 M), PGF(2 alpha) stimulated progesterone production in a biphasic manner, as middle concentrations significantly stimulated (10(-9) M) whereas low and high concentrations did not. In the presence of middle concentrations of PGF(2 alpha) (10(-9) M), GnRH significantly stimulated progesterone production in a linear concentration-dependent manner. Similar complexities were seen with respect to estradiol response. Thus, in the human GLC, GnRH potentiates the luteolytic effects of PGF(2 alpha), while it acts as a permissive factor for the luteotropic effects. Furthermore, we have revealed the complex interaction of these hormones using a three-dimensional experimental design.