Effects of pro-opiomelanocortin-derived peptides on adrenal steroidogenesis in guinea-pig adrenal cells in vitro

Abstract

The specific control of adrenal androgen secretion is unclear. This study was undertaken to investigate the effects of peptides derived from the ACTH precursor molecule pro-opiomelanocortin (POMC) on cortisol and androgen production using isolated guinea-pig adrenal cells. ACTH 10 −13−10 −9M, stimulated steroid production in a dose dependent manner, reaching a maximum of 12, 10 and 7 times basal levels for cortisol, androstenedione (A4) and dehydroepiandrosterone (DHEA), respectively, measured by specific radioimmunoassays. β-Lipotropin (β-LPH), 10 −10−10 −8M, also stimulated steroid production, reaching 6, 5 and 5 times basal levels of cortisol, A4 and DHEA, respectively. The N-terminal 16K fragment, λ 3- and β-MSH stimulated steroid production which reached statistical significance ( P < 0.05) only in the case of cortisol. Joining peptide, α-, β- and γ-endorphin resulted in no significant change in steroid production. Met- and leu-enkephalin resulted in significant inhibition of DHEA production. POMC-derived peptides altered the steroid response to ACTH. β-LPH and 16K fragment significantly increased the cortisol and A4 responses to a low concentration of ACTH. β-LPH reduced the maximum cortisol and A4 responses to a high concentration of ACTH. This study suggests that β-LPH may have a role in modulation of adrenal steroidogenesis but yielded no evidence to support a role for POMC-derived peptides in preferential stimulation of adrenal androgen production in guinea-pig adrenal cells.