Possible Involvement of Ca²⁺-Calmodulin System in Cyclic AMP Action in Cholesterol Ester Hydrolytic Response to ACTH in Bovine Adrenocortical Cells

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In order to elucidate the relationship between cyclic AMP and the Ca²⁺-calmodulin system in the steroidogenic response to adrenocorticotropic hormone (ACTH), the effects of calmodulin inhibitors (trifluoperazine and W-7) on cortisol production and cellular cholesterol ester hydrolysis induced by ACTH or dibutyryl cyclic AMP in bovine adrenocortical cells were examined in the absence of extracellular Ca²⁺. These calmodulin inhibitors inhibited not only the cortisol production and the cholesterol ester hydrolysis induced by ACTH in the absence of extracellular Ca²⁺, but also inhibited the dibutyryl cyclic AMP-induced cortisol production and the cholesterol ester hydrolysis in the absence of extracellular Ca²⁺. These results suggested the possibility that cyclic AMP action was mediated by the Ca²⁺-calmodulin system in the activation process of cellular cholesterol ester hydrolysis in the steroidogenic response to ACTH.