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Stimulation of Corticosteroid Biosynthesis by Angiotensin I, [Des-Asp¹] Angiotensin I, Angiotensin II and [Des-Asp¹]-Angiotensin II in Bovine Adrenal Fasciculata Cells

Division of Endocrinology, Department of Medicine, School of Medicine, University of Geneva Geneva, Switzerland

Abstract

The effect of angiotensin I (AI), angiotensin II (All), [des-asp¹]AI, [des-asp¹]AII and [des-asp¹-arg²]AII on corticosteroid production in isolated fasciculata cells from bovine adrenals has been studied.

All and [des-asp¹]AII in concentrations ranging from 10^–9M to 10^–6M had a potent stimulatory effect on steroid biosynthesis. The dose-response curves for both peptides were identical. AI was about 3 times less potent than All and [des-asp¹]AII. The effect of AI was not due to its conversion to All. [des-asp¹]AI was as active as AI. No significant conversion to [des-asp¹]AII was observed. [des-asp¹-arg²]AII had only a minimal effect on steroidogenesis. The structural analog [sar¹,-ala⁸]AII inhibited all angiotensins specifically and competitively. The affinity of the cellular binding site was higher for All and [des-asp¹]AII than for [sar¹ala⁸]AII, but lower for AI and [des-asp¹]AI than for the inhibitor. Combination of submaximal doses of AI and All resulted in an additive effect on steroid production. By contrast, combination of maximal doses of both peptides had the same effect as All alone. These data demonstrate a potent steroidogenic activity for All as well as AI, [des-asp¹] AI and [des-asp¹]AII in bovine adrenal fasciculata cells. A common receptor site for all four peptides is suggested.

Footnotes

Supported by the Swiss National Science Foundation grant No. 3.2300.74 and No. 4.7930.72. R.H. was supported by the Deutsche Forschungsgemeinschaft and the Fondation Suisse de Cardiologie.

Received April 20, 1976.

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