TESTOSTERONE MEDIATES EXPRESSION OF THE SELENOPROTEIN PHGPX BY INDUCTION OF SPERMATOGENESIS AND NOT BY DIRECT TRANSCRIPTIONAL GENE ACTIVATION

Selenium deficiency is known to be associated with male infertility, a nd the selenoprotein PHGPx has been shown to increase in rat testis af ter puberty and to depend on gonadotropin stimulation in hypophysectom ized rats [Roveri et al. (1992) J. Biol. Chem. 267, 6142-6146]. Exposu re of decapsulated whole testis, however, failed to reveal any transcr iptional activation or inhibition of the PHGPx gene by testosterone, h uman chorionic gonadotropin, or forskolin. Nevertheless, it was verifi ed that the specific activity of PHGPx in testis, but not of cGPx, cor related with sexual maturation. Leydig cell destruction in vivo by eth ane dimethane sulfonate (EDS) resulted in a delayed decrease in PHGPx activity and mRNA that could be completely prevented by testosterone s ubstitution. cGPx transiently increased upon EDS treatment, probably a s a result of reactive macrophage augmentation. In situ mRNA hybridiza tion studies demonstrated an uncharacteristic low level of cGPx transc ription in testis, whereas PHGPx mRNA was abundantly and preferentiall y expressed in round spermatids. The data show that the age or gonadot ropinciependent expression of PHGPx in testis does not result from dir ect transcriptional gene activation by testosterone, but is due to dif ferentiation stage-specific expression in late spermatids, which are u nder the control of Leydig cell-derived testosterone. The striking bur st of PHGPx expression at the transition of round to elongated spermat ids suggests an involvement of this selenoprotein in sperm maturation.