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.