AJP - Renal Watch the video to see how APS reaches out to developing nations.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Renal Physiol 290: F306-F312, 2006. First published September 27, 2005; doi:10.1152/ajprenal.00062.2005
0363-6127/06 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
290/2/F306    most recent
00062.2005v1
Right arrow Alert me when this article is cited
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 Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (4)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Thomas, C. P.
Right arrow Articles by Vats, H. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Thomas, C. P.
Right arrow Articles by Vats, H. S.

Medroxyprogesterone acetate binds the glucocorticoid receptor to stimulate {alpha}-ENaC and sgk1 expression in renal collecting duct epithelia

Christie P. Thomas,1,2,3 Kang Z. Liu,1 and Hemender S. Vats1

1Department of Internal Medicine and the 2Graduate Program in Molecular Biology, University of Iowa College of Medicine, and the 3Veterans Affairs Medical Center, Iowa City, Iowa

Submitted 13 February 2005 ; accepted in final form 23 September 2005

Medroxyprogesterone acetate (MPA), a widely used synthetic progestational contraceptive, occasionally leads to Cushingoid side effects such as hypertension, fluid retention, and centripetal obesity. We investigated the effect of MPA on classic mineralocorticoid target genes, {alpha}-epithelial Na channel (ENaC) and sgk1, in the collecting duct. In adrenalectomized mice, aldosterone, dexamethasone, and MPA increased {alpha}-ENaC mRNA levels in kidney cortex. MPA and dexamethasone, but not progesterone, dose dependently increased {alpha}-ENaC and sgk1 mRNA in M-1 and in Madin-Darby canine kidney-C7 cells, both collecting duct cell lines. The stimulatory effect of MPA and dexamethasone on {alpha}-ENaC expression was inhibited by RU-38486, a combined glucocorticoid receptor (GR) and progesterone receptor (PR) antagonist, but not by Org31710, a pure PR antagonist. MPA and dexamethasone dose dependently increased {alpha}-ENaC promoter-driven luciferase activity in M-1 cells, which was not inhibited by Org31710, indicating that MPA regulates {alpha}-ENaC in a PR-independent manner. When tested in HT29 cells, MPA could only stimulate {alpha}-ENaC-driven reporter activity when GR was coexpressed, confirming the requirement for functional GR in the transcriptional effect of MPA. The activation of steroid receptors such as GR can explain the apparent glucocorticoid effects of MPA, independent of PR activation.

epithelial sodium channel; Na+ transport; aldosterone; glucocorticoid response element


Address for reprint requests and other correspondence: C. P. Thomas, Division of Nephrology, Dept. of Internal Medicine, Univ. of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242-1081 (e-mail: christie-thomas{at}uiowa.edu)




This article has been cited by other articles:


Home page
 HypertensionHome page
P. A. Arias-Loza, K. Hu, A. Schafer, J. Bauersachs, T. Quaschning, J. Galle, V. Jazbutyte, L. Neyses, G. Ertl, K.-H. Fritzemeier, et al.
Medroxyprogesterone Acetate But Not Drospirenone Ablates the Protective Function of 17{beta}-Estradiol in Aldosterone Salt-Treated Rats
Hypertension, November 1, 2006; 48(5): 994 - 1001.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2006 by the American Physiological Society.