This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by ADAM, W. R. Articles by ULICK, S. Search for Related Content PubMed PubMed Citation Articles by ADAM, W. R. Articles by ULICK, S.

Amplification of the Action of Aldosterone by 5-Dihydrocortisol^*

Repatriation General Hospital (W.R.A.), Heidelberg 3077, Australia; Inserm U7, L'Hopital Necker (J.W.F.) Paris 75015, France
the Medical Research Centre, Prince Henry's Hospital (J.W.F., J.M.) Melbourne 3004, Australia
the Veterans Administration Hospital (S. U.) Bronx, New York 10468
the Department of Medicine, Mount Sinai School of Medicine of the City University of New York New York

Address all correspondence to: J. W. Funder, Prince Henry's Hospital, Melbourne 3004 Australia. Address requests for reprints to: S. Ulick, Veterans Administration Hospital, Bronx, New York 10468.

Abstract

Elevated conversion rates of cortisol to 5-dihydrocortisol (5-DHF) have been found in a child with hypoaldosteronism, Na⁺ retention, hypokalemic alkalosis, and hypertension. Studies investigating possible etiological roles for 5-DHF have shown in the rat urinary electrolyte bioassay in vivo that 5-DHF (30–100 µg/100 g) has minimal mineralocorticoid activity when administered alone, but the same dose administered with aldosterone (1 µg/100 g) doubles the mineralocorticoid response. Under identical conditions, cortisol was without effect. In the adrenalectomized rat kidney, in vitro, 5-DHF has 20% the affinity of dexamethasone for classical (type II) glucocorticoid receptors, 10% the affinity of corticosterone for (type III) corticosteroid-binding globulin-like glucocorticoid receptors, and 3% the affinity of aldosterone for mineralocorticoid receptors (type I). 5-DHF has <0.1% the affinity of dihydrotestosterone in mouse kidney receptors and <0.1% the affinity of both estradiol and progesterone for their receptors in rat uterus. As 5-DHF has low affinity for mineralocorticoid receptors and an effect (aldosterone amplification) totally outside the ambit of classical steroid effects, it may belong to a new physiological class of steroid hormones.

Footnotes

^* This work was presented in part at the 27th InternationalCongress of Physiological Sciences, Paris, 1977. It was supported by grants-in-aid from the National Heart Foundation of Australia, the National Health and Medical Research Council of Australia, the USPHS (AM-14040–09 and HL-18102–01), and the VA.

Received August 1, 1977.