Follicle-stimulating hormone--regulated granulosa cell steroidogenesis: involvement of the calcium-calmodulin system

The role of the calcium-calmodulin system in the gonadotropic regulation of ovarian steroidogenesis was studied by investigating the influence of various agents known to alter calcium metabolism or calmodulin activity on basal and follicle-stimulating hormone (FSH)-stimulated production of progesterone by rat granulosa cells in vitro. Lanthanum, a specific calcium antagonist, attenuated FSH-stimulated cyclic adenosine monophosphate (cyclic AMP) and progesterone production. [Ethylene-bis(oxyethylene-nitrilo)]tetraacetic acid (EGTA) significantly reduced this steroidogenic response but failed to alter the synthesis of the nucleotide. Although progesterone production was markedly increased by dibutyryl cyclic AMP, this was significantly lowered by an inhibitor of calcium uptake, verapamil. FSH-stimulated production of cyclic AMP and progesterone and dibutyryl cyclic AMP-induced progesterone biosynthesis were all significantly reduced by trifluoperazine, a specific inhibitor of calmodulin. These results indicate the existence of at least two sites in the trophic regulation of granulosa cell steroidogenesis which are calcium- and calmodulin-dependent: one localized at the level of cyclic AMP production, and the second at an unidentified step(s) distal to the formation of this nucleotide.