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Horm Metab Res 2004; 36(6): 381-386
DOI: 10.1055/s-2004-814572
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© Georg Thieme Verlag Stuttgart · New York

The Role of Progesterone Metabolism and Androgen Synthesis in Renal Blood Pressure Regulation

M.  Quinkler1 , S.  Diederich1 , V.  Bähr1 , W.  Oelkers1
  • 1Division of Medical Sciences, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham, UK and Division of Endocrinology, Charité, Klinikum Benjamin Franklin, Freie Universität Berlin, Germany
Further Information

Publication History

Received 1 December 2003

Accepted after Revision 10 February 2004

Publication Date:
07 July 2004 (online)

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Abstract

11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) plays a crucial role in converting hormonally active cortisol into inactive cortisone, conferring specificity onto the human mineralocorticoid receptor (MR). Progesterone binds with even higher affinity to the MR, but acts as an MR antagonist. How aldosterone is able to keep its function as predominant MR ligand in clinical situations with high progesterone concentrations, such as pregnancy, is not clear. We have shown in vitro that the human kidney possesses an effective enzyme system that metabolizes progesterone to inactive metabolites in a process similar to the inactivation of cortisol by 11β-HSD2. In studies on patients with adrenal insufficiency, we have shown that the in vivo anti-mineralocorticoid activity of progesterone is diminished by inactivating metabolism of progesterone, local formation of the deoxycorticosterone mineralocorticoid from progesterone, and inhibition of 11β-HSD2 by progesterone and its metabolites resulting in decreased inactivation of cortisol and hence increased MR binding by cortisol. The enzymes involved in progesterone metabolism are also responsible for the capability of the human kidney to convert pregnenolone to DHEA and androstenedione leading to the formation of active androgens, testosterone and 5α-DH-testosterone. Locally produced androgens might be responsible for the observed difference in blood pressure between men and women and higher susceptibility to hypertension in men.

Key words

Progesterone - Androgens - Human kidney - Hypertension

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Dr. M. Quinkler, M. D.

Division of Medical Sciences · University of Birmingham · Queen Elizabeth Hospital

Edgbaston · Birmingham B15 2TH · UK

Phone: + 44 (121) 414 2764

Fax: + 44 (121) 415 8712

Email: M.O.Quinkler@bham.ac.uk