THE METABOLISM OF ALDOSTERONE

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Abstract
A study was made of the metabolism of synthetic dl- and d-aldosterone and biosynthetic d-aldosterone-4-C14 by surviving human liver slices, and of the metabolism of d-aldosterone by human kidney slices. After incubation of aldosterone with the tissue slices in a Krebs-Ringer-phosphate glucose medium at 37[degree]C, the media were subjected to fractional hydrolysis and extracted with chloroform. In this way, it was possible to study not only the metabolites of the substrate but also the formation of water soluble conjugates of these metabolites and of aldosterone. It was found that the major in vitro metabolite of aldosterone, using liver slices as a source of enzymes, was the glucuronide of a Ring A reduced [alpha]-ketolic steroid (A2). It was possible to show that this metabolite was identical to the tetrahydroaldosterone found in glucuronide conjugation in human urine. In addition, several other metabolites were isolated but in smaller quantities. These include metabolite A1, a possible stereoisomer of A2, two [image]4-3-ketonic, non reducing metabolites and a number of C14 substances characterized only by chromatographic mobilities. Chemically unchanged aldosterone was present in free, glucuronide and acid labile conjugation. Human kidney slices, in addition to producing small amounts of A2, did conjugate aldosterone in both the glucuronide and acid labile form. The intravenous infusion of d-aldosterone to an adrenalectomized patient resulted in the urinary excretion of A2-glucuronide, aldosterone-glucuronide and the mild acid labile aldosterone conjugate.