Document Detail


The hypertensiogenetic steroid 19-nor-progesterone does not influence cortisol inactivation by 11beta-hydroxysteroid dehydrogenase type 2.
MedLine Citation:
PMID:  19811365     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Julia Lepenies; Paul M Stewart; Marcus Quinkler
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinical and experimental hypertension (New York, N.Y. : 1993)     Volume:  31     ISSN:  1525-6006     ISO Abbreviation:  Clin. Exp. Hypertens.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-10-08     Completed Date:  2010-01-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9305929     Medline TA:  Clin Exp Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  376-9     Citation Subset:  IM    
Affiliation:
KfH Dialysis Center Bismarckstrasse, Berlin, Germany.
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MeSH Terms
Descriptor/Qualifier:
11-beta-Hydroxysteroid Dehydrogenase Type 2 / antagonists & inhibitors,  genetics,  metabolism*
Cell Line
Dose-Response Relationship, Drug
Enzyme Activation / drug effects
Humans
Hydrocortisone / metabolism*,  pharmacology
Hypertension / metabolism
Kidney / cytology,  drug effects,  metabolism
Norprogesterones / metabolism*,  pharmacology
Transfection
Chemical
Reg. No./Substance:
0/Norprogesterones; 472-54-8/19-norprogesterone; 50-23-7/Hydrocortisone; EC 1.1.1.146/11-beta-Hydroxysteroid Dehydrogenase Type 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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