Human Proopiomelanocortin-(79–96), a Proposed Cortical Androgen- Stimulating Hormone, Does not Affect Steroidogenesis in Cultured Human Adult Adrenal Cells*

Abstract

The existence of a cortical androgen-stimulating hormone (CASH), distinct from ACTH, regulating the secretion of human adrenal androgens has long been postulated. Recently, it has been reported that an 18-amino acid peptide, corresponding to the first part of the joining peptide of proopiomelanocortin [POMC-(79-96)], was able to stimulate the secretion of dehydroepiandrosterone from cultured human adult adrenocortical cells, but had no effect on cortisol production. We have studied the acute and long term effects of ACTH (10(-11) and 10(-9) M), CASH-18 (10(-8) M), or both on cortisol and dehydroepiandrosterone sulfate by human adult adrenocortical cells. Although ACTH increased steroid secretion and enhanced the steroidogenic responsiveness to further ACTH stimulation, CASH-18 alone or together with ACTH (10(-11) or 10(-9) M) had no effect. In addition, we were unable to demonstrate any specific binding of [125I]CASH-18 to human adrenocortical cells, although [125I] ACTH-(1-39) binds specifically to the same cell preparation.