MODULATION OF THE STEROIDOGENESIS OF CULTURED HUMAN GRANULOSA-LUTEIN CELLS BY GONADOTROPIN-RELEASING-HORMONE ANALOGS

GnRH analogs are widely used in reproductive medicine to create a hypogonadotropic hypogonadism. However, numerous animal studies have demonstrated a direct regulation of the gonadal function by GnRH. To ascertain this direct ovarian effect in humans, the steroidogenesis of cultured human granulosa cells was studied with or without GnRH and five of its agonists. Buserelin (D-Ser(But)6, desGly10) GnRH ethylamide, leuprorelin (D-Leu6, desGly10) GnRH ethylamide, H4055 (desGly10) GnRH ethylamide, and H4065 (D-Trp6, desGly10) GnRH ethylamide significantly enhanced estradiol secretion. In addition, buserelin induced a significant cell surface decrease that seemed to be mediated by cytoskeleton modifications. The two other molecules, GnRH and triptorelin (D-Trp6) GnRH), had no effect on estrogen secretion at any of the studied concentrations. Thus, despite similar pituitary effects, these agonists did not exhibit the same ovarian action. This may be accounted for by the differences found between pituitary and ovarian receptors. These results suggest that some GnRH analogs can modulate human granulosa cell steroidogenesis at least in the preovulatory period.