THE EFFECTS OF AGING ON THE EXPRESSION OF GLUTATHIONE S-TRANSFERASES IN THE TESTIS AND EPIDIDYMIS OF THE BROWN-NORWAY RAT

Glutathione S-transferases (GSTs), a family of isoenzymes, catalyze th e conjugation of glutathione to a variety of electrophiles, and protec t cellular constituents from electrophilic and oxidative attack. Aging is associated with an overall increase in oxidative stress and thus f ree radical production. The present study examines the immunocytochemi cal localization of Ya, Yc, Yb-1, Yb-2, Yo, and Yf GST subunits in the testis and epididymis of Brown Norway rats aged 3, 12, 18, and 24 mon ths. In the testis, neither Sertoli nor germ cells showed changes in t he GST staining pattern during aging. At 24 months, two types of Leydi g cells were noted. Some (peritubular) formed a distinct band at the p eriphery of the tubule while others were seen in the interstitial spac e. The peritubular cells were identified as Leydig cells by specific s taining for 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), a Leydig cell-specific marker. Both types of Leydig cells were intensely react ive for all GST subunits at all ages. In the epididymis, principal cel ls of all epididymal regions, except the proximal cauda region, showed no changes in GST expression at all ages examined, At 24 months, some principal cells of this region became greatly enlarged and vacuolated . These cells were unreactive for Yo, Yb-1, Yb-2, and Yc, while adjace nt normal-appearing principal cells maintained the same intensity of e xpression as seen in 3-month controls. In contrast, vacuolated princip al cells were reactive for the Ya subunit, while adjacent normal princ ipal cells were unreactive. These data indicate that selective changes occur in the expression of GSTs at 24 months in principal cells havin g both a normal and a vacuolated appearance. The underlying mechanism responsible for these changes with age is unresolved, but we speculate that they lose the ability to handle oxidative stress. Taken together , these data show that aging affects region-specific changes in GST ex pression in the epididymis and Leydig cell distribution in the testis.