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

Abstract

Summary. After intravenous and oral administration of radioactive aldosterone to normal subjects, 7.3 + 0.4 (SE) and 5.4 ± 0.5 (SE) %, respectively, of the dose was recovered from a 48-hour collection of urine as aldosterone released by mild acid hydrolysis (from aldosterone 18-glucuronide), and 35 + 5 (SE) and 39 + 4 (SE) %, respectively, was recovered as tetrahydroaldosterone after incubation with 1e3-glucuronidase.After intravenous and oral administration of 17-isoaldosterone-4-"4C to a similar group of subjects, 35 ± 3 (SE) and 53 ± 4 (SE) %, respectively, of the dose was recovered as 17-isoaldosterone released by acid and less than 5% as total metabolites after incubation with fl-glucuronidase. No detectable radioactivity (< 0.5%) could be recovered as tetrahydroaldosterone or as a compound with the expected chromatographic properties of tetrahydro-17-isoaldosterone. The total radioactivity in the neutral extracts was also relatively small (< 2%) after administration of either labeled aldosterone or 17-isoaldosterone. These results indicated that, due to lack of A-ring reduction of the molecule and the consequent slowing of hepatic clearance, 17-isoaldosterone is converted to an acid-labile conjugate (presumably 17-isoaldosterone 18-glucuronide) as the major metabolite. 17-Isoaldosterone was not secreted or converted to aldosterone to any significant extent in the normal subjects investigated.

The Metabolism and Secretion of Aldosterone in Elderly Subjects*

“…This indicates that the splanchnic extraction is lower in the elderly subjects (12). However, this effect cannot account for the full extent of the lowering of the MCR values (Table III).…”

“…The proportion of the oral compared with the intravenous dose excreted as the aldosterone released from the acid labile conjugate is similar (about 75%) for the young and elderly subjects (Table III). As the acid labile conjugate is the major extrahepatic route of metabolism (16,17), this indicates that the amount of such metabolism is not altered appreciably in elderly subjects (12). It therefore appears that some of the lowering of the MCR must be due to decreased hepatic blood flow.…”

“…In six of the elderly subjects, the MCR was determined in both whole blood and plasma as described elsewhere (11). Some of the data for males have been previously quoted in order to compare the metabolism of aldosterone and 17-isoaldosterone in normal young subjects (12). The aldosterone secretion rate was studied in the same subjects, usually 1 week later.…”

“…ambulatory and active before and after the administration of the radioactive material. One I.c, 0.01 ,ug aldosterone-7-'H was injected intravenously, and 0.35 tIc, 2.3 ,ug aldosterone-4-14C was given orally to the same subject simultaneously as previously described (12). Urine was then collected for 48 hours.…”

“…The methods used to measure the radioactivity as aldosterone in the neutral and acid extracts and tetrahydroaldosterone released by f8-glucuronidase from samples of the 48-hour urinary collection have also been described (12,13). The only difference in the methods of calculation used in this study compared with those of Flood and co-workers (12) was that the "4C/H ratio of aldosterone from the neutral estract was taken from the isotopic ratio of the peak fraction after column chromatography of the aldosterone diacetate I (after acetylation) in the present work. In addition, in the studies reported here, the secretion rate of aldosterone was measured by the method of Flood and co-workers (13) from the specific activity of the aldosterone (micrograms in 24 hours/per cent tritiated dose) released from the acid labile conjugate.…”