The hypertensiogenetic steroid 19-nor-progesterone does not influence cortisol inactivation by 11beta-hydroxysteroid dehydrogenase type 2.
19-nor-progesterone (19-nor-P) has the characteristics of a potent mineralocorticoid in adrenalectomized or salt-loaded rats and is capable of causing hypertension. In human placenta, progesterone is converted to 19-hydroxy-progesterone, a precursor of 19-nor-P. In some states of pregnancy hypertension, 19-nor-P may inhibit renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), thus allowing cortisol to bind to the mineralocorticoid receptor (MR). Therefore, we investigated the ability of 19-nor-P to inhibit human 11beta-HSD2. Fetal kidney cells (HEK 293) were transfected with human 11beta-HSD2 and incubated with increasing concentrations of 19-nor-P, labelled and unlabelled cortisol. Steroids were extracted, separated by TLC, and radioactivity was measured using a TLC scanner. 19-nor-P treatment did not significantly reduce 11beta-HSD2 activity (430 to 300 pmol/mg protein/h) in the range of tested concentrations. In conclusion, 19-nor-P did not inhibit human 11beta-HSD2 and seems not to be involved in human hypertension. Nevertheless, 19-nor-P may be converted by extra-adrenal tissues into 19-nor-deoxycorticosterone (DOC) or 19-nor-corticosterone, which are potent mineralocorticoids and may be involved in the pathogenesis of hypertension during pregnancy.
Lepenies
Julia
J
KfH Dialysis Center Bismarckstrasse, Berlin, Germany.
Stewart
Paul M
PM
Quinkler
Marcus
M
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism* / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009653:Norprogesterones / Q000378:metabolism* / Q000494:pharmacology; D014162:Transfection
D009653:Norprogesterones; C030703:19-norprogesterone; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D006854:Hydrocortisone