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Effects of forskolin on progesterone and cyclic adenosine monophosphate production in avian granulosa cells.

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 three agonists were combined, the oLH dose-response curve was left shifted by about two orders of magnitude (from ED50 of 9 ng/ml to 0.1 ng/ml). However, forskolin alone could not stimulate progesterone production to the same extent as oLH alone did, even though cyclic AMP levels in response to forskolin were higher than those observed in response to oLH. Moreover, whereas one to two orders to magnitude discrepancy exists between the steroidogenic and adenylate cyclase activating effects of LH, the efficacy of forskolin to provoke steroidogenesis and to increase cyclic AMP production in granulosa cells was found to be similar. Therefore, forskolin-promoted steroidogenesis appears to be a direct consequence of the activation of the adenylate cyclase/cyclic AMP system, whereas oLH-induced steroidogenesis, a receptor-mediated event, is probably more complex and may involve cellular events in addition to those regulated by cyclic AMP.