Effects of Forskolin on Progesterone and Cyclic Adenosine Monophosphate Production in Avian Granulosa Cells

Abstract

Forskolin, a novel activator of adenylate cyclase, promoted progesterone production by isolated chicken granulosa cells. At submaximal levels its steroidogenic action was greatly potentiated by isobutyl methylxanthine or the addition of submaximally stimulating concentrations of ovine luteinizing hormone (oLH). When all 3 agonists were combined, the oLH dose-response curve was shifted left by .apprx. 2 orders of magnitude (from ED50 of 9 to 0.1 ng/ml). However, forskolin alone could not stimulate progesterone production to the same extent as oLH alone did, even though cAMP levels in response to forskolin were higher than those observed in response to oLH. Moreover, whereas 1-2 orders of magnitude discrepancy exists between the steroidogenic and adenylate cyclase activating effects of LH, the efficacy of forskolin to provoke steroidogenesis and to increase cAMP production in granulosa cells was similar. Therefore, forskolin-promoted steroidogenesis appears to be a direct consequence of the activation of the adenylate cyclase/cAMP system, whereas oLH-induced steroidogenesis, a receptor-mediated event, is probably more complex and may involve cellular events in addition to those regulated by cAMP.