Identification of 19-norprogesterone in pregnant rat urine

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.

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The Hypertensiogenetic Steroid 19-nor-Progesterone does not Influence Cortisol Inactivation by 11β-Hydroxysteroid Dehydrogenase Type 2

Lepenies¹,

Stewart

Quinkler

2009

Clinical and Experimental Hypertension

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Identification of 19-norprogesterone in pregnant rat urine

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The Hypertensiogenetic Steroid 19-nor-Progesterone does not Influence Cortisol Inactivation by 11β-Hydroxysteroid Dehydrogenase Type 2

The Hypertensiogenetic Steroid 19-nor-Progesterone does not Influence Cortisol Inactivation by 11β-Hydroxysteroid Dehydrogenase Type 2

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