A Possible Regulatory Role of Ca⁺⁺-Calmodulin System in Cellular Cholesterol Ester Hydrolysis in the Steroidogenic Response to ACTH in Bovine Adrenocortical Cells

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order to corroborate the regulatory role of Ca⁺⁺-calmodulin system in the steroidogenic response to adrenocorticotropic hormone (ACTH), the effects of calmodulin inhibitors (chlorpromazine, trifluoperazine, and W-7) on cortisol production and cellular cholesterol ester hydrolysis induced by ACTH in bovine adrenocortical cells were examined.
Three calmodulin inhibitors diminished not only the cholesterol ester hydrolysis and cortisol production induced by ACTH in the presence of Ca++, but also inhibited the Ca⁺⁺-induced hydrolysis and cortisol production in the absence of ACTH. Neither cortisol production in crude mitochondrial fraction nor the ACTH-induced Ca⁺⁺-influx was affected by chlorpromazine.
These results indicate that Ca++-calmodulin system plays a significant regulatory role in the supply of free cholesterol to the adrenal mitochondria in the steroidogenic response to ACTH.