Possible endogenous regulators of steroid inactivating enzymes and glucocorticoid-induced Na+ retention.
Various endogenous substances which bear similar structural resemblances to glycyrrhetininc acid were screened for inhibitory activity against 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) and 5 beta-reductase (5 beta-R). Among the compounds screened, 3 alpha, 5 beta-tetrahydroprogesterone (3 alpha,5 beta-THP) was a potent inhibitor of 11 beta-OHSD and a moderate inhibitor of 5 beta-R. Of the bile acids tested, chenodeoxycholic acid (CDCA) was the most potent inhibitor of both 11 beta-OHSD and 5 beta-R. Cholic acid (CA), a moderate inhibitor of 11 beta-OHSD was a weak inhibitor of 5 beta-R, whereas deoxycholic acid was a moderate inhibitor of 5 beta-R but a weak inhibitor of 11 beta-OHSD. 3 alpha, 5 beta-THP and bile acids were also tested to determine whether, like GA, they could confer mineralocorticoid actions upon corticosterone (B). In adrenalectomized rats pretreated with CDCA or 3 alpha,5 beta-THP, B caused a significant antinatriuresis; the effect of B plus CDCA was blocked by the antimineralocorticoid, RU 28318. Thus, we report on two structurally similar endogenous substances, 3 alpha, 5 beta-THP and CDCA, which inhibit both 11 beta-OHSD and 5 beta-R activity, and which can confer mineralocorticoid actions upon the glucocorticoid, B.
Latif
S A
SA
Department of Pathology, Miriam Hospital, Providence, Rhode Island 02906.
Hartman
L R
LR
Souness
G W
GW
Morris
D J
DJ
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000315:Adrenalectomy; D000818:Animals; D002635:Chenodeoxycholic Acid / Q000494:pharmacology*; D005938:Glucocorticoids / Q000378:metabolism; D006034:Glycyrrhetinic Acid / Q000494:pharmacology*; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000187:drug effects; D007668:Kidney / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000187:drug effects; D011188:Potassium / Q000378:metabolism / Q000652:urine; D011280:Pregnanolone / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism / Q000652:urine*
D005938:Glucocorticoids; D002635:Chenodeoxycholic Acid; D011374:Progesterone; D012964:Sodium; D011280:Pregnanolone; D010088:Oxidoreductases; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; C021936:3-oxo-5 beta-steroid delta 4-dehydrogenase; D006034:Glycyrrhetinic Acid; D011188:Potassium