DIFFERENTIAL EXPRESSION OF GLUTATHIONE-S-TRANSFERASE ISOFORMS IN COMPARTMENTS OF THE TESTIS AND SEGMENTS OF THE EPIDIDYMIS OF THE RAT

Specific cell types of the mammalian testes demonstrate varying suscep tibility to toxic insult by chemical agents. The mammalian testis is d ivided into two major compartments: seminiferous tubules, the site of spermatogenesis, and interstitium, which contains the Leydig cells. Gl utathione S-transferase (GST) expression was examined in isolated comp artments of the rat testis and in segments of the epididymis. Western blot analysis revealed the presence of GST class alpha, mu, and pi ban ds in each of the isolated compartments of the testis, and HPLC analys is of monomeric isoforms provided evidence for differential expression of multiple GST isoforms in testicular compartments. All major isofor ms (e.g., forms 1, 2, 3, 4, 6, 7, 8, 9, and 11) were detected in the c ytosol of whole testis. Isoform subunit 4 was the major form in the tu bule, whereas isoform subunit 11 is the dominant form in the Leydig ce lls. Isoform subunits 3, 4, and 6 were enriched in the tubules as comp ared to interstitial or Leydig cells. The preferential action of repro ductive toxicants at specific stages of aging may be due to an age-dep endent expression of the activating or detoxifying enzymes in the repr oductive tract. Therefore, the age-dependent expression of testicular GST isoforms was also examined. Expression of isoform subunits 2 and 4 displayed an age dependence, with the largest increase in these subun its occurring between ages 4 and 15 weeks. Isoform expression did not correlate with serum testosterone levels. HPLC analysis of the GST iso forms in the longitudinal segments of the epididymis and vas deferens revealed differential expression within these segments. Total GST prot ein and catalytic activity was highest in the caput epididymis and pro gressively decreased toward the vas deferens. Isoform subunit 2 was th e major form expressed in the epididymis. The results of this study in dicate that the GSTs are differentially expressed in testicular compar tments and epididymal segments, and that this may contribute to suscep tibility of different cell types to xenobiotic damage.