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.
Morris
D J
DJ
McDermott
M J
MJ
Freiberger
M
M
Latif
S A
SA
Pacholski
M
M
Brem
A S
AS
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