11 alpha- and 11 beta-hydroxyprogesterone, potent inhibitors of 11 beta-hydroxysteroid dehydrogenase (isoforms 1 and 2), confer marked mineralocorticoid activity on corticosterone in the ADX rat.
The effects of 11 alpha- and 11 beta-hydroxyprogesterone (11 alpha-OHP, 11 beta-OHP), on the activity of the glucocorticoid inactivating enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) were studied. 11 alpha-OHP and 11 beta-OHP were potent inhibitors of both 11 beta-HSD1 in rat liver microsomes and 11 beta-HSD2 in lysates of JEG-3 cells, a human choriocarcinoma cell line. In addition, both progesterone metabolites were markedly potent in conferring mineralocorticoid activity upon B in the adrenalectomized rat. These results provide insight into the structural properties required of inhibitors of 11 beta-HSD activity and indicate a possible role for endogenous 11 beta-HSD inhibitors in the regulation of glucocorticoid-induced Na+ retention.
Souness
G W
GW
Department of Pathology and Laboratory Medicine, Miriam Hospital, Providence, RI.
Latif
S A
SA
Laurenzo
J L
JL
Morris
D J
DJ
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000315:Adrenalectomy; D000818:Animals; D002822:Choriocarcinoma / Q000201:enzymology; D003345:Corticosterone / Q000494:pharmacology*; D006801:Humans; D006908:Hydroxyprogesterones / Q000494:pharmacology*; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D009318:Natriuresis / Q000187:drug effects; D011188:Potassium / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured
D006908:Hydroxyprogesterones; C030228:11-hydroxyprogesterone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D011188:Potassium; D003345:Corticosterone