The metabolism of aldosterone in kidney.
Slices of kidney cortex and medulla from adrenalectomized male rats metabolized aldosterone to at least 4 peaks of polar metabolites as well as reduced metabolites. The majority of the products were ring A-reduced and shown chromatographically to consist of 5 alpha-reduced metabolites; significant quantities of 5 beta-reduced metabolites were also synthesized. Approximately half of the 5 alpha-reduced products cochromatographed with 3 beta,5 alpha-THA and the remainder with 5 alpha-DHA and/or 3 alpha,5 alpha-THA. The anti-mineralocorticoids, spironolactone and progesterone, inhibited renal synthesis of 5 alpha-reduced products of aldosterone by 80%. 5 beta-Reduction was also slightly inhibited. Corticosterone slightly inhibited synthesis of the 5 alpha- and 5 beta-reduced products. Corticosterone and progesterone significantly inhibited the renal synthesis of the polar metabolites of aldosterone, but the inhibition was not significant at this dosage of spironolactone. Interestingly, the nuclei and plasma membranes were shown to be the most active fractions for these aldosterone transformations. Importantly significant quantities of 5 alpha-DHA and/or 3 alpha,5 alpha-THA, which possess 1/10 and 1/30, respectively, of the antinatriuretic activity of aldosterone, were synthesized at these subcellular locations.
D000315:Adrenalectomy; D000450:Aldosterone / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003345:Corticosterone / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013148:Spironolactone / Q000494:pharmacology
C013282:tetrahydroaldosterone; D013148:Spironolactone; D000450:Aldosterone; D011374:Progesterone; C018920:5-dihydroaldosterone; D003345:Corticosterone