This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bamberger, C. M. Articles by Schulte, H. M. Search for Related Content PubMed PubMed Citation Articles by Bamberger, C. M. Articles by Schulte, H. M.

Dissociative Glucocorticoid Activity of Medroxyprogesterone Acetate in Normal Human Lymphocytes¹

Department of Medicine (C.M.B., F.U.B.) and Institute for Pathology (A.-M.B.), University Hospital Eppendorf, 20246 Hamburg; and the IHF Institute for Hormone and Fertility Research, University of Hamburg (C.M.B., T.E., H.M.S.), 22529 Hamburg, Germany

Address all correspondence and requests for reprints to: Christoph M. Bamberger, M.D., Department of Medicine, University Hospital Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany. E-mail: bamberger{at}uke.uni-hamburg.de

The immunosuppressive effects of glucocorticoids (GC) have led to their wide application in the treatment of inflammatory and autoimmune states. However, long term GC treatment is associated with severe side-effects. The development of agents displaying a more favorable ratio of wanted and unwanted GC effects, is, therefore, a major goal of pharmacological and clinical research. In this study, the progesterone receptor agonist medroxyprogesterone acetate (MPA), which also binds to the glucocorticoid receptor (GR), was tested with regard to its immunosuppressive properties. Using a recently established electroporation protocol, we show that MPA (but not progesterone) can suppress a human interleukin-2 (IL-2) promoter-luciferase construct to the same extent as the synthetic GC dexamethasone in normal human lymphocytes. MPA also markedly suppressed IL-2 (as well as IL-1 and IL-6) release, as assessed by specific enzyme-linked immunosorbent assays. In contrast, a highly dexamethasone-inducible glucocorticoid response element-driven promoter construct was only marginally stimulated by MPA in both normal human lymphocytes and HeLa cells. RT-PCR and Western blot analysis of normal human lymphocytes revealed that they do not express progesterone receptor messenger ribonucleic acid and protein, respectively. In contrast, the GR protein was clearly detectable in all samples and was shown to mediate the effects of MPA in transfected Jurkat T lymphoma cells. Our data indicate that 1) MPA can transrepress the human IL-2 gene in normal human lymphocytes in the absence of significant trans-activation; and 2) this effect is mediated by GR. Because of its dissociative GC activity, MPA is a highly promising substance for the treatment of inflammatory/autoimmune states.

This article has been cited by other articles:

				C Dosiou, A E Hamilton, Y Pang, M T Overgaard, S Tulac, J Dong, P Thomas, and L C Giudice Expression of membrane progesterone receptors on human T lymphocytes and Jurkat cells and activation of G-proteins by progesterone J. Endocrinol., January 1, 2008; 196(1): 67 - 77. [Abstract] [Full Text] [PDF]

				M. Schumacher, R. Guennoun, A. Ghoumari, C. Massaad, F. Robert, M. El-Etr, Y. Akwa, K. Rajkowski, and E.-E. Baulieu Novel Perspectives for Progesterone in Hormone Replacement Therapy, with Special Reference to the Nervous System Endocr. Rev., June 1, 2007; 28(4): 387 - 439. [Abstract] [Full Text] [PDF]

				J. L. Turgeon, M. C. Carr, P. M. Maki, M. E. Mendelsohn, and P. M. Wise Complex Actions of Sex Steroids in Adipose Tissue, the Cardiovascular System, and Brain: Insights from Basic Science and Clinical Studies Endocr. Rev., October 1, 2006; 27(6): 575 - 605. [Abstract] [Full Text] [PDF]

				C. P. Thomas, K. Z. Liu, and H. S. Vats Medroxyprogesterone acetate binds the glucocorticoid receptor to stimulate {alpha}-ENaC and sgk1 expression in renal collecting duct epithelia Am J Physiol Renal Physiol, February 1, 2006; 290(2): F306 - F312. [Abstract] [Full Text] [PDF]

				T. P. Burris and V. Krishnan Estrogen: A Mitochrondrial Energizer That Keeps on Going Mol. Pharmacol., October 1, 2005; 68(4): 956 - 958. [Abstract] [Full Text] [PDF]

				P. Smit, H. Russcher, F. H. de Jong, A. O. Brinkmann, S. W. J. Lamberts, and J. W. Koper Differential Regulation of Synthetic Glucocorticoids on Gene Expression Levels of Glucocorticoid-Induced Leucine Zipper and Interleukin-2 J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2994 - 3000. [Abstract] [Full Text] [PDF]

				K. Pazol, M. E. Wilson, and K. Wallen Medroxyprogesterone Acetate Antagonizes the Effects of Estrogen Treatment on Social and Sexual Behavior in Female Macaques J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2998 - 3006. [Abstract] [Full Text] [PDF]

				J. L. Turgeon, D. P. McDonnell, K. A. Martin, and P. M. Wise Hormone Therapy: Physiological Complexity Belies Therapeutic Simplicity Science, May 28, 2004; 304(5675): 1269 - 1273. [Abstract] [Full Text] [PDF]

				K. De Bosscher, W. Vanden Berghe, and G. Haegeman The Interplay between the Glucocorticoid Receptor and Nuclear Factor-{kappa}B or Activator Protein-1: Molecular Mechanisms for Gene Repression Endocr. Rev., August 1, 2003; 24(4): 488 - 522. [Abstract] [Full Text] [PDF]

				T. A. Henderson, P. T. K. Saunders, A. Moffett-King, N. P. Groome, and H. O. D. Critchley Steroid Receptor Expression in Uterine Natural Killer Cells J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 440 - 449. [Abstract] [Full Text] [PDF]

				D. Rachon, A. Wakatsuki, Y. Okatani, N. Ikenoue, and T. Fukaya The Antiinflammatory Properties of Medroxyprogesterone Acetate * Response Circulation, November 26, 2002; 106 (22): e185 - e185. [Full Text] [PDF]