Comparative fates of intravenously and orally administered aldosterone: evidence for extrahepatic formation of acid-hydrolyzable conjugate in man.

Abstract

It is well established that the liver is a major site of metabolic inactivation of aldosterone. In 1962 Coppage, Island, Cooner, and Liddle (2) reported that the human liver was capable of converting aldosterone both to its acid-hydrolyzable conjugate (AHC) 1 and to tetrahydroaldosterone. The same study also demonstrated that aldosterone was almost completely inactivated during a single passage through the normal liver. More recent studies by Luetscher and associates (4) have indicated that the normal liver extracts about 97%o of the aldosterone delivered to it by the arterial circulation, and the studies of Bougas and co-workers (5, 6) have indicated that in subjects with minimal cardiac dysfunction the rate of splanchnic clearance of aldosterone amounts to about 89%o of the hepatic blood flow.The fact that the liver metabolizes almost all of the aldosterone presented to it does not imply that the liver is the only site of metabolism of aldosterone. Sandor and Lanthier (7) observed that kidney slices could convert aldosterone to AHC. From their analyses of hepatic and peripheral venous plasma after the continuous infusion of tritiated aldosterone into human subjects, Bougas and co-workers (5,6)

A Comparison of the Metabolism of Radioactive 17-Isoaldosterone and Aldosterone Administered Intravenously and Orally to Normal Human Subjects*

“…An analogous explanation has been given by Bledsoe and co-workers (2) feature of structure, such as the acetal at 11,18. The acid lability may be due to a similar structural feature.…”

“…In contrast, after both oral and intravenous administration of aldosterone, about 35 %o is recovered as tetrahydroaldosterone after incubation of the urine with 8-glucuronidase. Also, after oral administration of the natural hormone, only 8%o is released by mild acid hydrolysis as aldosterone (corrected for recovery of the released aldosterone), and after intravenous injection, the corresponding quantity is 10% (2,5,10). The difference in excretion of aldosterone in the acid extract after oral compared to intravenous injection of aldosterone has been postulated as being due to high hepatic extraction of aldosterone with some extrahepatic conversion of the intravenous aldosterone to the acid-labile conjugate (2,14).…”

“…All the radioactive compounds administered 2 were finally purified on a 60-cm column 1 cm in diameter with 28 g Celite and 14 ml methanol-water (1: 1 vol: vol) as the stationary phase. Benzene was the mobile phase.…”

“…The statistical accuracy of the ratio (K7) of "C to 'H for aldosterone in the neutral extract was therefore about 25%. The splanchnic extraction (H) can be calculated as (1 -Kir) 100% (2). For normal subjects with greater than 90% extraction, the standard error in the estimation of H is therefore maximally 3%o.…”

“…The radioactive compound in the pooled fractions of the major peak was administered orally with an intravenous injection of aldosterone-7-3H to normal subjects. This was part of a study on the metabolism of aldosterone using an approach similar in principle to that employed by Bledsoe and co-workers (2).…”