title: 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.affiliation: Population Council, Center for Biomedical Research, 1230 York Avenue, New York, New York 10021, USA.
authors.forename: Wing-Yee
authors.initials: WY
authors.lastname: Lui
authors.forename: Yan Ho
authors.initials: YH
authors.lastname: Cheng
authors.forename: Dolores D
authors.initials: DD
authors.lastname: Mruk
authors.forename: Chin Ho
authors.initials: CH
authors.lastname: Cheng
authors.forename: Meng Yun
authors.initials: MY
authors.lastname: Mo
authors.forename: Will M
authors.initials: WM
authors.lastname: Lee
authors.forename: C Yan
authors.initials: CY
authors.lastname: Cheng
mesh_terms: D000818:Animals; D004343:Drug Implants; D005786:Gene Expression Regulation; D006498:Hepatectomy; D015151:Immunoblotting; D007249:Inflammation; D008099:Liver / Q000378:metabolism*; D008297:Male; D009919:Orchiectomy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013530:Surgical Wound Infection / Q000378:metabolism*; D013737:Testis / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology; D000511:alpha-Macroglobulins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D004343:Drug Implants; D012333:RNA, Messenger; D000511:alpha-Macroglobulins; D013739:Testosterone