α-Human Artial Natriuretic Polypeptide Inhibits Steroidogenesis in Cultured Human Adrenal Cells*

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Abstract
The ability of synthetic α-human atrial natriuretic polypeptide-(l–28) (αhANP) to alter steroidogenesis byhuman adrenal glands was investigated in primary human adrenal cell cultures. ahANP (10−9–10−7 M) inhibited basal and ACTH (10−8 M)-stimulated aldosterone, cortisol, and dehydroepiandrosterone (DHEA) secretion in a dose-dependent manner. ahANP inhibited aldosterone (IC50, 1.3 × 10−8 M) and cortisol (IC50, 0.7 × 10−8 M) secretion more potently than it did DHEA (IC50,7.5 × 10−8 M) secretion. ACTH dose-dependent (10-10–10−8 M) increases in aldosterone, cortisol, and DHEA secretion were significantly inhibited by αhANP (10−8 M). In addition, ahANP enhanced the accumulation of intracellular cGMP in a dose-dependent manner. As aldosterone, cortisol, and DHEA secretion from cultured human adrenal cells was inhibited by ahANP, the site of inhibition of steroidogenesis by αhANP is probably localized in the early pathway of steroidogenesis in human adrenal cells. The results also suggest a link between inhibitory effects of αhANP and accumulation of intracellular cGMP.