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

Third Department of Internal Medicine, Faculty of Medicine, Kyushu University Fukuoka 812
Department of Biochemistry, Miyazaki Medical College Kiyotake, Miyazaki 889-16, Japan

Address requests for reprints to: Dr. Kazumi Higuchi, Third Department of Internal Medicine, Kyushu University, Fukuoka 812, Japan.

The ability of synthetic -human atrial natriuretic polypeptide-(l–28) (hANP) 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 x 10^–8 M) and cortisol (IC_50, 0.7 x 10^–8 M) secretion more potently than it did DHEA (IC_50,7.5 x 10^–8 M) secretion. ACTH dose-dependent (10^-10–10^–8 M) increases in aldosterone, cortisol, and DHEA secretion were significantly inhibited by hANP (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 hANP is probably localized in the early pathway of steroidogenesis in human adrenal cells. The results also suggest a link between inhibitory effects of hANP and accumulation of intracellular cGMP.

^* This work was supported in part by Research Grant 60480273 from the Ministry of Eduction of Japan.

Received September 18, 1985.

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