Population Council Research that makes a difference

Abstract

α-macroglobulin expression in the liver in response to inflammation is mediated by the testis 
Lui,Wing-Yee; Cheng,Yan Ho; Mruk,Dolores D.; Cheng,Chin Ho; Mo,Meng-Yun; Lee,Will M.; Cheng,Chuen-yan
Journal of Endocrinology 185(3): 497-505
Publication date: 2005


Earlier studies have shown that germ cells or germ cell-conditioned media are capable of regulating α-macroglobulin (α-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 α-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 α-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 α-MG in the liver. However, castration induced a mild but not statistically significant induction of α-MG in the liver in contrast to sham operation or hemicastration alone, when hemicastration alone could induce liver α-MG production by almost fourfold. Perhaps most important of all, hepatectomy accompanied by castration significantly reduced the liver α-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 α-MG response to experimentally induced inflammation in the liver. Interestingly, this lack of response of the liver to surgery-induced inflammation regarding α-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 α-MG expression in response to inflammation possibly via testosterone or testosterone-induced biological factor(s).