Differential effect of cadmium on GSH-peroxidase activity in the Leydig and the Sertoli cells of rat testis. Suppression by selenium and the possible relationship to heme concentration.
In the testes of rats treated with cadmium acetate (7 or 20 mumoles/kg, 24 hr, s.c.), the activity of glutathione (GSH)-peroxidase was increased. At the same time, the activity of glutathione disulfide (GSSG)-reductase and the cellular GSH concentration were decreased significantly. The basal activity of peroxidase in the Leydig and the Sertoli cell populations was comparable. However, the magnitude of increases in the activities markedly differed in the two cell populations, with that of the Sertoli cells increasing to nearly 450% of the control value in response to treatment with 20 mumoles/kg Cd2+. In the Leydig cells, the enzyme activity in response to the same treatment increased to only about 170% of the control value. Cd2+ treatment increased the concentration of heme in the microsomal and the smooth and rough endoplasmic reticulum fractions of the whole testis, as well as in the microsomal fractions of the Leydig and the Sertoli cells. As with the peroxidase activity, the two cell populations vastly differed in their susceptibilities to Cd2+ treatment, with the Sertoli cells being more severely affected by the metal. In the Sertoli cells the microsomal heme concentration was increased by approximately 11-fold, whereas only a 2-fold increase in the Leydig cells was noted. The increase in GSH-peroxidase activity was not due to the peroxidase activity of GSH-S-transferases, insofar as an increase in transferase activity was not observed in the Leydig and the Sertoli cells. Treatment of rats with sodium selenite (10 mumoles/kg, s.c.) 30 min before Cd2+ treatment (20 mumoles/kg) fully suppressed the above-described spectrum of effects of Cd2+ in the testis. Also, sodium selenite at a lower dose of 5 mumoles/kg prevented an increase in GSH-peroxidase activity. It is hypothesized that increased GSH-peroxidase activity in the Leydig and the Sertoli cells constitutes an adaptive response to increased cellular levels of heme and to the free radicals generated by the heme molecule. Selenium prevents the increase in GSH-peroxidase activity by circumventing the increase in cellular heme concentration. The protection is believed to be related, at least in part, to increased production of cellular GSH.
D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000032:analysis*; D005980:Glutathione Reductase / Q000032:analysis; D005982:Glutathione Transferase / Q000032:analysis; D006418:Heme / Q000032:analysis*; D007985:Leydig Cells / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000494:pharmacology*; D012708:Sertoli Cells / Q000187:drug effects / Q000201:enzymology*
D002104:Cadmium; D006418:Heme; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D012643:Selenium