In vitro regulation of extracellular superoxide dismutase in sertoli cells

Rat Sertoli and germ cells express extracellular superoxide dismutase (SODE X), however, the relative level of SODEX expressed by these cells was not k nown. We report herein germ cells consisting largely of spermatogonia, sper matocytes, and round spermatids expressed only one-third SODEX as that of S ertoli cells when examined by semi-quantitative RT-PCR. While cocultures of germ cells with Sertoli cells failed to induce any changes in SODEX expres sion possibly due to the limited number of cells that can be supported by t he in vitro culture system dissimilar to the in vivo condition, incubation of total germ cell-conditioned medium with Sertoli cells was able to signif icantly inhibit Sertoli cell SODEX expression dose-dependently suggesting a germ cell-derived soluble factor(s) may regulate SODEX in the testis. On t he other hand, cytokines such as TGF-beta(1), beta-NGF, or FGF and steroid hormones such as estradiol-17 beta, progesterone, testosterone, and DHT wer e unable to effect the expression of Sertoli cell SODEX. However, FSH at 10 0 ng/dish was able to induce a significant increase in Sertoli cell SODEX e xpression. While cytokines, the known mediators of the inflammatory respons e, were unable to affect Sertoli cell SODEX expression, the induction of ge neralized inflammation in vivo was able to cause a 2- to 2.5-fold increase in testicular SODEX expression concomitant with a transient increase in the liver but not in the brain. Taken collectively, these results demonstrate that while SODEX is an important antioxidant enzyme protecting the testis f rom reactive oxygen species, the mechanism(s) regulating its expression may involve an array of molecules and is a complicated cellular event. (C) 200 0 Elsevier Science Inc. All rights reserved.