Response of α2-macroglobulin messenger ribonucleic acid expression to acute inflammation in the testis is different from the response in the liver and brain

Abstract

Recent studies from this laboratory have shown that Sertoli cells derived from 20-day-old rats and cultured in vitro synthesize and secrete a nonspecific protease inhibitor that is structurally and immunologically similar to serum α2-macroglobulin (α2-MG). In contrast to its serum homologue, the testicular α2-MG is not an acute-phase protein in the rat since its protein concentration in the rete-testis fluid does not increase in response to inflammation. In the present study we examined the expression of α2-MG mRNA in the rat testis in comparison to that in the brain and liver following induced inflammation. α2-MG mRNA in the testis did not respond to induced inflammation, whereas its protein concentration in serum and its mRNA level in the brain and liver increased significantly in 20-day-old inflamed rats. In 8-day-old rat testis, where the blood-testis barrier is not yet formed, α2-MG mRNA expression also did not respond to induced inflammation. The mRNA expression of clusterin, another authentic Sertoli cell protein whose secretion appears to be closely related to cell-cell interactions in the seminiferous epithelium, was shown to be unaffected by induced inflammation in the testis, brain, and liver. In view of the unexpected differential expression of α2-MG mRNA to induced inflammation in the testis and liver, we sought to examine whether Sertoli cell α2-MG would respond to FSH and testosterone (T), the major regulators of testicular function. Interestingly, expression of α2-MG and clusterin mRNA in the Sertoli cell was not regulated by FSH, T, or a combination of FSH and T. Since there is an intimate morphological relationship between Sertoli cells and germ cells, we next examined the effect of germ cell-conditioned medium (GCCM) on Sertoli cell α2-MG and clusterin mRNA expression. It was noted that GCCM caused a dose-dependent stimulation of α2-MG and inhibition of clusterin mRNA expression in Sertoli cells, respectively. Therefore, our studies have shown that the regulatory mechanism that modulates the expression of α2-MG mRNA in the rat testis is different from its counterpart in the brain and liver.