Oxandrolone blocks glucocorticoid signaling in an androgen receptor-dependent manner

Steroids
Jingbo ZhaoChristopher P Cardozo

Abstract

The anabolic steroid oxandrolone is increasingly used to preserve or restore muscle mass in those with HIV infection or serious burns. These effects are mediated, in part, by the androgen receptor (AR). Anti-glucocorticoid effects have also been reported for some anabolic steroids, and the goal of our studies was to determine whether oxandrolone had a similar mechanism of action. Studies with in vitro translated glucocorticoid receptor (GR), however, showed no inhibition of cortisol binding by oxandrolone. Conversely, experiments in cell culture systems demonstrated significant antagonism of cortisol-induced transcriptional activation by oxandrolone in cells expressing both the AR and GR. Inhibition was not overcome by increased cortisol concentration, and no inhibition by oxandrolone was observed in cells expressing GR alone, confirming that non-competitive mechanisms were involved. AR-dependent repression of transcriptional activation by oxandrolone was also observed with the synthetic glucocorticoids dexamethasone and methylprednisolone. Furthermore, the AR antagonists 2-hydroxyflutamide and DDE also repressed GR transactivation in an AR-dependent manner. A mutant AR lacking a functional nuclear localization signal (AR(4RKM)...Continue Reading

References

Nov 1, 1975·The American Journal of Physiology·M Mayer, F Rosen
Sep 1, 1992·The Journal of Steroid Biochemistry and Molecular Biology·J A SimentalE M Wilson
Aug 1, 1987·Journal of Steroid Biochemistry·A J SymsR G Smith
Sep 1, 1973·Clinical Pharmacology and Therapeutics·A KarimH I Maibach
Dec 1, 1993·The Journal of Steroid Biochemistry and Molecular Biology·N WarriarM V Govindan
Jan 15, 1996·The Journal of Clinical Investigation·G TiaoP O Hasselgren
Dec 10, 1998·The Journal of Endocrinology·P Sohoni, J P Sumpter
Apr 20, 1999·JAMA : the Journal of the American Medical Association·A StrawfordM K Hellerstein
Jul 22, 1999·The European Respiratory Journal·R H van BalkomC L van Herwaarden
Aug 24, 1999·Current Opinion in Clinical Nutrition and Metabolic Care·P O Hasselgren
Apr 17, 2001·Annals of Surgery·D W HartD N Herndon
Jun 19, 2001·Molecular and Cellular Endocrinology·C SultanJ Nicolas
Feb 21, 2002·Molecular Biology of the Cell·Steven M MarkusMichael J Garabedian
Mar 30, 2002·Molecular Endocrinology·Helmut DotzlawAria Baniahmad
Aug 13, 2002·Chest·Shing-Shing YehUNKNOWN M012 Study Group
Oct 31, 2002·JPEN. Journal of Parenteral and Enteral Nutrition·Carrie P EarthmanWanda H Howell
Feb 1, 2003·Archives of Biochemistry and Biophysics·Christopher P CardozoAvrom J Caplan
Nov 18, 2003·Proceedings of the National Academy of Sciences of the United States of America·Inez RogatskyKeith R Yamamoto
Nov 11, 2006·Lung·David R GrimmMarvin Lesser

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Citations

Nov 9, 2004·Pediatric Research·James G Tidball, Michelle Wehling-Henricks
May 25, 2005·Annals of Surgery·C T PereiraD N Herndon
Mar 19, 2009·ILAR Journal·Zejing WangRainer Storb
Jul 22, 2009·Journal of Strength and Conditioning Research·Jay R HoffmanAlan D Rogol
Oct 6, 2009·Advances in Chronic Kidney Disease·Kirsten L Johansen
Jul 2, 2008·The Journal of Steroid Biochemistry and Molecular Biology·Huei-Ju Ting, Chawnshang Chang
Oct 31, 2006·The Journal of Steroid Biochemistry and Molecular Biology·Sara SaponaroFrancesca Silvagno
Feb 10, 2006·Annals of the New York Academy of Sciences·Jonathan P Jarow, Barry R Zirkin
Jul 3, 2013·Biochemical and Biophysical Research Communications·Yong WuChristopher Cardozo
Jun 9, 2018·International Journal of Molecular Sciences·Dana M OtzelJoshua F Yarrow
Apr 12, 2011·Current Opinion in Endocrinology, Diabetes, and Obesity·Stephanie T Page
Jan 23, 2008·Arquivos brasileiros de endocrinologia e metabologia·Rodrigo S FortunatoDenise P de Carvalho
Feb 11, 2020·Trends in Endocrinology and Metabolism : TEM·Jan KroonOnno C Meijer

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