Further study of aldosterone secretion-inhibitory factor and brain natriuretic peptide on cortisol production of guinea pig zona fasciculata cells

The suppressive effect of aldosterone secretion-inhibitory factor (ASIF) and brain natriuretic peptide (BNP-32) on the basal and ACTH-stimulated cortisol production in a primary culture enriched with guinea pig Zona Fasciculata (ZF) cells was further studied. The binding of 125I-labeled ACTH(1-24) and ASIF to ZF cells was found to be displaced by ACTH(1-24), Phe2, Nle4 and Ala24]-ACTH(1-24), ASIF, and BNP in a concentration-dependent manner. The binding of 125I-labeled Phe2, Nle4 and Ala24]-ACTH(1-24) to two transformed clones of mammalian cells expressing the guinea pig ACTH receptor was also competitively inhibited by ASIF and BNP. ASIF and BNP significantly suppressed ACTH-stimulated cAMP production in ZF cells. The 10- and 30-min cellular changes in cAMP induced by ASIF and BNP did not correlate in the rank order with the ultimate magnitude of cortisol suppression observed in ZF cells after a 24-hour treatment with these peptides. Nevertheless, the results did conform to the signaling mechanism of their action. Overall, the findings clearly demonstrated that ASIF and BNP suppressed the adrenocortical function and inhibited ACTH for their antagonistic action against ACTH primarily at the ACTH receptor site. These results support the notion that a physiological role of adrenal medulla in regulating the adrenocortical function may be mediated by the neuropeptides through a paracrine pathway.