Alpha2-macroglobulin expression in the liver in response to inflammation is mediated by the testis

J Endocrinol. 2005 Jun;185(3):497-505. doi: 10.1677/joe.1.06136.


Earlier studies have shown that germ cells or germ cell-conditioned media are capable of regulating alpha2-macroglobulin (alpha2-MG, a non-specific protease inhibitor) expression by Sertoli cells and hepatocytes cultured in vitro. These results illustrate a possible physiological link between testes and liver regarding alpha2-MG production. Using a series of surgical procedures including castration, hemicastration, and hepatectomy coupled with Northern blot and immunoblot analyses, we report herein that the surge in alpha2-MG expression in the liver in response to inflammation is indeed regulated, at least in part, by the testis via testosterone. It was found that hepatectomy induced at least a tenfold increase in the steady-state mRNA and protein production of alpha2-MG in the liver. However, castration induced a mild but not statistically significant induction of alpha2-MG in the liver in contrast to sham operation or hemicastration alone, when hemicastration alone could induce liver alpha2-MG production by almost fourfold. Perhaps most important of all, hepatectomy accompanied by castration significantly reduced the liver alpha2-MG response to the surgery-induced inflammation compared with hepatectomy alone, illustrating that the removal of the testicles can induce a loss of signal communications between the testis and the liver, rendering a significant loss of the alpha2-MG response to experimentally induced inflammation in the liver. Interestingly, this lack of response of the liver to surgery-induced inflammation regarding alpha2-MG production following castration could be restored, at least in part, by using testosterone implants placed subdermally 6 days prior to orchiectomy. Collectively, these results illustrate that a physiological link does indeed exist between the testis and the liver, and that testes per se can influence the liver in vivo alpha2-MG expression in response to inflammation possibly via testosterone or testosterone-induced biological factor(s).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Drug Implants
  • Gene Expression Regulation
  • Hepatectomy
  • Immunoblotting
  • Inflammation
  • Liver / metabolism*
  • Male
  • Orchiectomy
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Surgical Wound Infection / metabolism*
  • Testis / metabolism*
  • Testosterone / pharmacology
  • alpha-Macroglobulins / analysis
  • alpha-Macroglobulins / genetics
  • alpha-Macroglobulins / metabolism*


  • Drug Implants
  • RNA, Messenger
  • alpha-Macroglobulins
  • Testosterone