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

Abstract

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).

• Authors: Wing-Yee Lui, Yan Ho Cheng, Dolores D Mruk, Chin Ho Cheng, Meng Yun Mo, Will M Lee, C Yan Cheng
• Journal: The Journal of endocrinology (J Endocrinol) Vol. 185 Issue 3 Pg. 497-505 (Jun 2005) ISSN: 0022-0795 [Print] England
• PMID: 15930176 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

• 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, genetics, metabolism)