Comparison of effects of adrenocorticotropin and Lys-gamma 3-melanocyte-stimulating hormone on steroidogenesis, adenosine 3',5'-monophosphate production, and phospholipid metabolism in rat adrenal fasciculata-reticularis cells in vitro

Abstract

Synthetic bovine Lys-gamma 3MSH was found to potentiate the steroidogenic action of ACTH during incubation of rat adrenal fasciculata-reticularis cells in vitro. On the other hand, Lys-gamma 3MSH did not increase basal levels of or ACTH-induced (submaximal) increases in cellular concentrations of cAMP or phosphatidylinositol. Thus, Lys-gamma 3MSH does not appear to simply increase the overall action of ACTH, and moreover, it appears to potentiate steroidogenesis by a mechanism that is considerably different from that employed by ACTH. Observance of an effect of ACTH and failure to observe an effect of gamma 3MSH on adrenal phosphatidylinositol are in keeping with our previous postulation that phospholipids in the phosphatidate-inositide cycle play an important role in promoting cholesterol side-chain cleavage, since ACTH, but not gamma 3MSH, reportedly increases cholesterol side-chain cleavage. In addition, we also presently observed that Lys-gamma 3MSH can markedly increase corticosterone production in the face of a fixed, relatively small, submaximal, ACTH-induced increase in phosphatidylinositol. Thus, if gamma 3MSH enhances steroidogenesis by increasing free cholesterol availability, the latter may require another factor to initiate steroidogenesis, but is, nevertheless, an important determinant of the rate of steroidogenesis.