Article Text

PDF
Evidence That Androgens Modulate Human Thymic T Cell Output
  1. Nancy J. Olsen*,
  2. William J. Kovacs
  1. From the *Divisions of Rheumatology, and †Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The Pennsylvania State University, College of Medicine, Milton S. Hershey Medical Center, Hershey,PA.
  1. Received August 23, 2010, and in revised form October 7, 2010.
  2. Accepted for publication October 8, 2010.
  3. Reprints: William J. Kovacs, MD, Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The Pennsylvania State University, College of Medicine, Milton S. Hershey Medical Center, H044, 500 University Dr, Hershey, PA 17033-0850. E-mail: wkovacs{at}hmc.psu.edu.
  4. These studies were supported by a grant (AG 029999) from the National Institutes of Health.

Abstract

Background The thymus has long been recognized as a target for the actions of androgenic hormones, but it has only been recently recognized that alterations in circulating levels of gonadal steroids might affect thymic output of T cells. We had the opportunity to examine parameters of thymic cellular output in several hypogonadal men undergoing androgen replacement therapy.

Methods Circulating naive (CD4+CD45RA+) T cells were quantitated by flow cytometric analysis of peripheral blood mononuclear cells. Cells bearing T-cell receptor excision circles were quantitated using real-time polymerase chain reaction amplification of DNA isolated from peripheral blood mononuclear cells from healthy men and from hypogonadal men before and after testosterone replacement therapy.

Results CD4+CD45+ (naive) T cells comprised 10.5% of lymphocytes in healthy males; this proportion was greatly increased in 2 hypogonadal men (35.5% and 44.4%). One man was studied sequentially during treatment with physiologic doses of testosterone. CD4+CD45RA+ cells fell from 37.36% to 20.05% after 1 month and to 12.51% after 7 months of normalized androgen levels. In 2 hypogonadal patients, T-cell receptor excision circle levels fell by 83% and 78% after androgen replacement therapy.

Conclusions Our observations indicate that the hypogonadal state is associated with increased thymic output of T cells and that this increase in recent thymic emigrants in peripheral blood is reversed by androgen replacement.

Key Words
  • androgens
  • thymus
  • recent thymic emigrants
  • T cells

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.