Article
The hypertensiogenetic steroid 19-nor-progesterone does not inhibit renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2)
Das hypertensiogene Steroid 19-nor-Progesteron hemmt nicht die 11beta-Hydroxysteroid Dehydrogenase 2 (11beta-HSD2) in der Niere
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Authors
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M.O. Quinkler
- Charité Campus Mitte, Berlin (Berlin, D)
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I.J. Bujalska
- University of Birmingham, Queen Elizabeth Hospital (Birmingham, GB)
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P.M. Stewart
- University of Birmingham, Queen Elizabeth Hospital (Birmingham, GB)
| Published: | August 8, 2006 |
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Outline
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It was observed that 19-nor-progesterone (19-nor-P) has the characteristics of a potent mineralocorticoid in adrenalectomized or salt-loaded rats and, as such, is capable of causing hypertension. These results seem to be species-specific, because 19-nor-P did not increase blood pressure in sheep. In human placenta progesterone is converted to 19-hydroxy-progesterone, which is a precursor of 19-nor-P. Studies at the human mineralocorticoid receptor (MR) revealed no transactivation properties of 19-nor-P. Nevertheless, 19-nor-P may inhibit renal 11beta-HSD2 in some states of pregnancy hypertension, thus allowing cortisol to bind to the 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 cultured in Eagle medium with 10% fetal calf serum. After reaching 70% confluence, cells were incubated in triplicate in serum-free media with increasing concentrations of 19-nor-P (1-1000 nmol/l), 100,000 cpm tritiated cortisol and 50nmol/l unlabelled cortisol. After 3 hours, steroids were extracted from the supernatant, separated by using thin layer chromatography (TLC) and radioactivity was measured using a TLC scanner. Protein concentrations were measured in each well.
Control cells showed a 11beta-HSD2 activity of 430 pmol/mg protein/h. 19-nor-P treatment reduced 11beta-HSD2 activity, but not significant, to approximately 300 pmol/mg protein/h at a concentration of 10 to 1000nmol/l.
In conclusion, 19-nor-P did not inhibit human 11beta-HSD2. Nevertheless, it is possible that 19-nor-P is converted by extra-adrenal tissues into 19-nor-deoxycorticosterone (DOC) in biologically active quantities. 19-nor-DOC is a potent mineralocorticoid, and may have a role in regulating systemic arterial pressure and may be involved in the pathogenesis of hypertension, especially during pregnancy.
