gms | German Medical Science

29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Hochdruckliga e. V. DHL ® - Deutsche Hypertonie Gesellschaft Deutsches Kompetenzzentrum Bluthochdruck

23. bis 25.11.2005, Berlin

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

Meeting Abstract

Suche in Medline nach

  • M.O. Quinkler - Charité Campus Mitte, Berlin (Berlin, D)
  • I.J. Bujalska - University of Birmingham, Queen Elizabeth Hospital (Birmingham, GB)
  • P.M. Stewart - University of Birmingham, Queen Elizabeth Hospital (Birmingham, GB)

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP8

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2005/05hoch008.shtml

Veröffentlicht: 8. August 2006

© 2006 Quinkler et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

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.