STIMULATION OF ALDOSTERONE BIOSYNTHESIS IN VITRO BY SEROTONIN

Abstract

ABSTRACT The dialysable fraction of rat serum, which was previously shown to stimulate aldosterone production in rat adrenal sections, was chromatographed on Sephadex G-25. Fluorescence spectra indicated that a 5-hydroxyindole derivative was present in the active eluate fraction. The aldosterone-stimulating activity of serum dialysate had a similar retention volume to serotonin and 5-hydroxytryptophan, but was separated from other indole derivatives. Addition of small amounts of pure serotonin to the incubation medium led to a significant and dose-dependent increase of aldosterone and deoxycorticosterone production but did not affect corticosterone production. At higher concentrations, 5-methoxytryptamine, bufotenine and 5-hydroxytryptophan also stimulated aldosterone biosynthesis, whereas a number of other substances chemically or pharmacologically related to serotonin were found to be inactive. Two different serotonin antagonists completely blocked the aldosterone-stimulating effects of serotonin and rat serum but did not influence aldosterone stimulation by ACTH. Serotonin stimulated the incorporation of tritiated cholesterol into aldosterone but not the incorporation of tritiated pregnenolone, indicating that it acts on the conversion of cholesterol to pregnenolone.