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.
AuthorsJulia Lepenies, Paul M Stewart, Marcus Quinkler
JournalClinical and experimental hypertension (New York, N.Y. : 1993) (Clin Exp Hypertens) Vol. 31 Issue 4 Pg. 376-9 (Jun 2009) ISSN: 1525-6006 [Electronic] England
PMID19811365 (Publication Type: Journal Article)
Chemical References
  • Norprogesterones
  • 19-norprogesterone
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2
  • Hydrocortisone
  • 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

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