The effects of antimineralocorticoids on synthesis of aldosterone metabolites in target tissues.
[3H]Aldosterone is transformed into several metabolites by subcellular fractions of rat kidney. 80-90% of the metabolites synthesized by nuclei and plasma membranes are 5 alpha-DHAldo and 3 alpha,5 alpha-THAldo in ratios of 1:2 and 1:1 respectively; small quantities of 3 beta,5 alpha-THAldo are also synthesized. In contrast, kidney cytosol metabolizes Aldo principally to 5 beta-reduced products with co-chromatograph with 5 beta-DHAldo and 3 alpha,5 beta-THAldo. Several polar neutral metabolites, as well as sulfate and acidic metabolites are also synthesized by the cytosol fraction. Similar 5 alpha-reduced metabolites, 5 alpha-DHAldo, 3 alpha,5 alpha-THAldo and 3 beta,5 alpha-THAldo are also synthesized when [3H]aldosterone is incubated in vitro with toad urinary bladder for 1 and 5 h. Significant quantities of 5 beta- and 20 beta-reduced products and sulfate and acidic metabolites are also synthesized. The metabolism of [3H]aldosterone in both target tissues is significantly inhibited by aldosterone antagonists. Several of the reduced metabolites of aldosterone synthesized in kidney and toad bladder possess significant mineralocorticoid activity. 5 alpha-DHAldo and 3 alpha,5 alpha-THAldo possess 1/10 and 1/30 and 3 alpha,5 beta possesses 1/80-1/100 of the antinatriuretic activity of Aldo. It is suggested that the metabolism of Aldo in its target tissues may be linked to regulation or expression of the hormone's actions.
D J
DJ
Morris
M J
MJ
McDermott
M
M
Freiberger
S A
SA
Latif
M
M
Pacholski
A S
AS
Brem
D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D002025:Bufonidae; D002191:Canrenoic Acid / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D014316:Tritium; D001743:Urinary Bladder / Q000378:metabolism
D000451:Mineralocorticoid Receptor Antagonists; D014316:Tritium; D000450:Aldosterone; D011374:Progesterone; D002191:Canrenoic Acid; D003345:Corticosterone