help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Quinkler, M.
Right arrow Articles by Diederich, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Quinkler, M.
Right arrow Articles by Diederich, S.
The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 11 4165-4171
Copyright © 1999 by The Endocrine Society

Original Studies

Progesterone Metabolism in the Human Kidney and Inhibition of 11ß-Hydroxysteroid Dehydrogenase Type 2 by Progesterone and Its Metabolites1

Marcus Quinkler, Sarah Johanssen, Claudia Großmann, Volker Bähr, Markus Müller, Wolfgang Oelkers and Sven Diederich

Departments of Endocrinology (M.Q., S.J., C.G., V.B., W.O. S.D.) and Urology (M.M.), Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, 12200 Berlin, Germany

Address correspondence and requests for reprints to: Marcus Quinkler, M.D., Division of Endocrinology, Universitätsklinikum Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.

Progesterone binds with high affinity to the mineralocorticoid (MC) receptor, but confers only very low agonistic MC activity. Therefore, progesterone is a potent MC antagonist in vitro.

Although progesterone reaches up to 100 times higher plasma levels in late pregnancy than aldosterone, the in vivo MC antagonistic effect of progesterone seems to be relatively weak. One explanation for this phenomenon could be local metabolism of progesterone in the human kidney, similar to the inactivation of cortisol to cortisone by the 11ß-hydroxysteroid dehydrogenase (11ß-HSD) type 2. We studied the metabolism of progesterone in the human kidney in vitro and found reduction to 20{alpha}-dihydro (DH)-progesterone as the main metabolite. Ring-A reduction to 5{alpha}-DH-progesterone, 20{alpha}-DH-5{alpha}-DH-progesterone, and 3ß,5{alpha}-tetrahydro (TH)-progesterone was also documented. We further showed for the first time that 17-hydroxylation of progesterone (17{alpha}-OH-progesterone, 17{alpha}-OH, 20{alpha}-DH-progesterone), normally localized in the adrenals and the gonads, occurs in the human adult kidney. We found no formation of deoxycorticosterone from progesterone in the human adult kidney. Using human kidney cortex microsomes, we tested the inhibitory potency of progesterone and its metabolites on the 11ß-HSD type 2. The most potent inhibitor was progesterone itself (IC50 = 4.8 x 10-8 mol/L), followed by 5{alpha}-DH-progesterone (IC50 = 2.4 x 10-7 mol/L), 20{alpha}-DH-progesterone, 3ß,5{alpha}-TH-progesterone, 17{alpha}-OH-progesterone, and 20{alpha}-DH-5{alpha}-DH-progesterone (IC50 between 7.7 x 10-7 mol/L and 1.3 x 10-6 mol/L). The least potent inhibitor was 17{alpha}-OH,20{alpha}-DH-progesterone. In addition to progesterone metabolism by the kidney, the inhibition of 11ß-HSD type 2 by progesterone and its metabolites could be a second explanation for the weak MC-antagonist activity of progesterone in vivo. Inhibition of 11ß-HSD type 2 leads to an increase of intracellular cortisol in a way that the local equilibrium between the MC agonist cortisol and the antagonist progesterone is shifted to the agonist side.




This article has been cited by other articles:


Home page
 EndocrinologyHome page
M. Myers, M. C. Lamont, S. van den Driesche, N. Mary, K. J. Thong, S. G. Hillier, and W. C. Duncan
Role of Luteal Glucocorticoid Metabolism during Maternal Recognition of Pregnancy in Women
Endocrinology, December 1, 2007; 148(12): 5769 - 5779.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
J Bryndova, P Klusonova, M Kucka, K Mazancova-Vagnerova, I Miksik, and J Pacha
Cloning and expression of chicken 20-hydroxysteroid dehydrogenase
J. Mol. Endocrinol., December 1, 2006; 37(3): 453 - 462.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
V. E. Murphy, R. Smith, W. B. Giles, and V. L. Clifton
Endocrine Regulation of Human Fetal Growth: The Role of the Mother, Placenta, and Fetus
Endocr. Rev., April 1, 2006; 27(2): 141 - 169.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
F. Hammer, D. G. Drescher, S. B. Schneider, M. Quinkler, P. M. Stewart, B. Allolio, and W. Arlt
Sex Steroid Metabolism in Human Peripheral Blood Mononuclear Cells Changes with Aging
J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 6283 - 6289.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
M. Quinkler, B. Sinha, J. W Tomlinson, I. J Bujalska, P. M Stewart, and W. Arlt
Androgen generation in adipose tissue in women with simple obesity - a site-specific role for 17{beta}-hydroxysteroid dehydrogenase type 5
J. Endocrinol., November 1, 2004; 183(2): 331 - 342.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Quinkler, B. Meyer, W. Oelkers, and S. Diederich
Renal Inactivation, Mineralocorticoid Generation, and 11{beta}-Hydroxysteroid Dehydrogenase Inhibition Ameliorate the Antimineralocorticoid Effect of Progesterone in Vivo
J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3767 - 3772.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Quinkler and P. M. Stewart
Hypertension and the Cortisol-Cortisone Shuttle
J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2384 - 2392.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Quinkler, C. Bumke-Vogt, B. Meyer, V. Bahr, W. Oelkers, and S. Diederich
The Human Kidney Is a Progesterone-Metabolizing and Androgen-Producing Organ
J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2803 - 2809.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
L. M. Thurston, K. C. Jonas, D. R. E. Abayasekara, and A. E. Michael
Ovarian Modulators of 11{beta}-Hydroxysteroid Dehydrogenase (11{beta}HSD) Activity in Follicular Fluid from Bovine and Porcine Large Antral Follicles and Spontaneous Ovarian Cysts
Biol Reprod, June 1, 2003; 68(6): 2157 - 2163.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. Diederich, E. Eigendorff, P. Burkhardt, M. Quinkler, C. Bumke-Vogt, M. Rochel, D. Seidelmann, P. Esperling, W. Oelkers, and V. Bahr
11{beta}-Hydroxysteroid Dehydrogenase Types 1 and 2: An Important Pharmacokinetic Determinant for the Activity of Synthetic Mineralo- and Glucocorticoids
J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5695 - 5701.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
C. O. Stocco, J. Chedrese, and R. P. Deis
Luteal Expression of Cytochrome P450 Side-Chain Cleavage, Steroidogenic Acute Regulatory Protein, 3{beta}-Hydroxysteroid Dehydrogenase, and 20{alpha}-Hydroxysteroid Dehydrogenase Genes in Late Pregnant Rats: Effect of Luteinizing Hormone and RU486
Biol Reprod, October 1, 2001; 65(4): 1114 - 1119.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
N. Farman and M.-E. Rafestin-Oblin
Multiple aspects of mineralocorticoid selectivity
Am J Physiol Renal Physiol, February 1, 2001; 280(2): F181 - F192.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Odermatt, P. Arnold, and F. J. Frey
The Intracellular Localization of the Mineralocorticoid Receptor Is Regulated by 11beta -Hydroxysteroid Dehydrogenase Type 2
J. Biol. Chem., July 20, 2001; 276(30): 28484 - 28492.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1999 by The Endocrine Society