Evidence that androgens modulate human thymic T cell output

J Investig Med. 2011 Jan;59(1):32-5. doi: 10.2310/jim.0b013e318200dc98.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Androgens / pharmacology*
  • Androgens / therapeutic use
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • Hormone Replacement Therapy
  • Humans
  • Hypogonadism / drug therapy
  • Leukocyte Common Antigens / metabolism
  • Male
  • Middle Aged
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / drug effects*
  • Thymus Gland / cytology*


  • Androgens
  • Receptors, Antigen, T-Cell
  • Leukocyte Common Antigens