α2-Macroglobulin expression in the liver in response to inflammation is mediated by the testis

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Article (peer-reviewed)

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Earlier studies have shown that germ cells or germ cell-conditioned media are capable of regulating α2-macroglobulin (α2-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 α2-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 α2-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 α2-MG in the liver. However, castration induced a mild but not statistically significant induction of α2-MG in the liver in contrast to sham operation or hemicastration alone, when hemicastration alone could induce liver α2-MG production by almost fourfold. Perhaps most important of all, hepatectomy accompanied by castration significantly reduced the liver α2-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 α2-MG response to experimentally induced inflammation in the liver. Interestingly, this lack of response of the liver to surgery-induced inflammation regarding α2-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 α2-MG expression in response to inflammation in vivo possibly via testosterone or testosterone-induced biological factor(s).






Probing Studies in Male Contraception