Suppression of adrenocorticotropic hormone (ACTH)-induced corticosterone secretion in cultured rat adrenocortical cells by gossypol and gossypolone.

We have reported that gossypol, an antifertility agent, and gossypolone, a major metabolite of gossypol, inhibited steroidogenesis in bovine luteal cells in vitro. In the current study, the effects of these two compounds on steroidogenesis were examined in adrenocortical cells of young rats. ACTH-induced corticosterone secretion and intracellular adenosine monophosphate (cAMP) formation were significantly inhibited by gossypol at concentrations of 8.6 and 4.3 microM, respectively, and by gossypolone at concentrations of 8.6 and 4.3 microns, respectively. The present study demonstrated that both compounds inhibit ACTH-induced corticosterone synthesis and secretion in rat adrenocortical cell and this inhibition is, at least partially, attributed to the reduction of intracellular cAMP formation. Our data suggest that gossypol and its metabolite(s) probably affect steroidogenesis not only in gonads but also in adrenal glands by a common mean-reduction of intracellular cAMP.