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Dose-Response Relationships Between Plasma Adrenocorticotropin (ACTH), Cortisol, Aldosterone, and 18-Hydroxycorticosterone After Injection of ACTH-(1–39) or Human Corticotropin-Releasing Hormone in Man^*

Division of Endocrinology, Department of Internal Medicine, Klinikum Steglitz, Freie Universität Berlin Berlin, West Germany

Address requests for reprints to: W. Oelkers, M.D., Department of Internal Medicine, Klinikum Steglitz, Freie Universität Berlin, Hindenburgdamm 30, 1000 Berlin 45, West Germany.

The effects of sc injections (at 1500 h) of increasing amounts of synthetic human ACTH-(l–39) (1.25–30 µg) on plasma ACTH, cortisol, aldosterone, and 18-hydroxycorticosterone were compared with those of iv injections of 30 and 100 µg synthetic human CRH in nine normal men. Five micrograms of ACTH, sc, was the lowest dose that significantly increased plasma levels of the three steroids. CRH (30 µg, iv) increased plasma cortisol and 18-hydroxycorticosterone, but not aldosterone, while 100 µg CRH also raised aldosterone secretion. The dose-response curve (peak plasma ACTH level vs. maximum increment of plasma cortisol within the first hour) was initially very steep. Plasma ACTH levels between 50 and 60 ng/L (11–13 pmol/L) stimulated cortisol to almost 80% of the maximal increment obtained with plasma ACTH levels above 300 ng/L (>66 pmol/L). This dose-response relationship is similar to that found in clinical tests of the pituitary-adrenal axis (insulin test, metyrapone test). The effects of plasma ACTH released by CRH on cortisol secretion were not significantly different from those of injected ACTH. Our results argue against the hypothesis that the effect of CRH on steroid secretion is mediated or modulated by POMC-derived peptides other than ACTH.

^* This work was supported by a grant of the Deutsche Forschungsgemeinschaft (Oe 47/8-2).

Received June 18, 1987.

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