HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/5/E856    most recent 00484.2005v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Page, S. T. Articles by Wu, J. D. Search for Related Content PubMed PubMed Citation Articles by Page, S. T. Articles by Wu, J. D.

Effect of medical castration on CD4⁺CD25⁺ T cells, CD8⁺ T cell IFN- expression, and NK cells: a physiological role for testosterone and/or its metabolites

¹Department of Medicine and ⁴Department of Urology, University of Washington; ²Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington; ³National Oregon Primate Research Center, Beaverton, Oregon; and ⁵Fred Hutchinson Cancer Research Center, Seattle, Washington

Submitted 4 October 2005 ; accepted in final form 7 December 2005

The higher prevalence of autoimmune disease among women compared with men suggests that steroids impact immune regulation. To investigate how sex steroids modulate cellular immune function, we conducted a randomized trial in 12 healthy men aged 35–55 yr treated for 28 days with placebo, a GnRH antagonist, acyline to induce medical castration, or acyline plus daily testosterone (T) gel to replace serum T, followed by a 28-day recovery period. Serum hormones were measured weekly and peripheral blood lymphocytes (PBLs) were collected biweekly for analyses of thymus-derived lymphocyte (T cell) subtypes and natural killer (NK) cells. Compared with the other groups and to baseline throughout the drug exposure period, men receiving acyline alone had significant reductions in serum T (near or below castrate levels), dihydrotestosterone, and estradiol (P < 0.05). Medical castration significantly reduced the percentage of CD4⁺CD25⁺ T cells (P < 0.05), decreased mitogen-induced CD8⁺ T cell IFN- expression, and increased the percentage of NK cells without affecting the ratio of CD4⁺ to CD8⁺ T cells and the expression of NK cell-activating receptor NKG2D or homing receptor CXCR1. No changes in immune composition were observed in subjects receiving placebo or acyline with replacement T. These data suggest that T and/or its metabolites may help maintain the physiological balance of autoimmunity and protective immunity by preserving the number of regulatory T cells and the activation of CD8⁺ T cells. In addition, sex steroids suppress NK cell proliferation. This study supports a complex physiological role for T and/or its metabolites in immune regulation.

testosterone replacement; gonadotropin-releasing hormone antagonist; regulatory T cells; interferon-

This article has been cited by other articles:

				L. Arruvito, M. Sanz, A. H. Banham, and L. Fainboim Expansion of CD4+CD25+and FOXP3+ Regulatory T Cells during the Follicular Phase of the Menstrual Cycle: Implications for Human Reproduction J. Immunol., February 15, 2007; 178(4): 2572 - 2578. [Abstract] [Full Text] [PDF]