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Inhibition of cortisol production by aldosterone secretion-inhibitory factor and brain natriuretic peptides.

Circumstantial evidence has indicated that the adrenal gland may produce certain factors regulating its own corticoid production through a paracrine pathway. The putative factors play only a subtle role modulating adrenocortical function in response to ACTH. Aldosterone secretion-inhibitory factor (ASIF) and brain natriuretic peptides (BNP) are among the attractive candidates. ASIF was tested in a primary culture system of guinea-pig adrenal zona fasciculata (ZF) cells and found to be effective in suppressing both the basal and ACTH-stimulated cortisol production in a dose-dependent manner. At the effective doses, ASIF was not toxic to the cells in culture morphologically but attenuated the growth-stimulating action of ACTH. Tested with three types of natriuretic peptides in the same cell culture system, we found that BNP was as effective as ASIF. Studies on the relationship between peptide primary structures and activities revealed that the inhibitory activity of ASIF on cortisol production required an intact Cys-Cys loop with both N- and C-terminal extensions from Cys residues of not less than 2 amino acids.