Differential regulation of male rat liver glutathione S-transferases: Effects of orchidectomy and hormone replacement

The effects of orchidectomy and hormone replacement on glutathione S-transferase activities in adult male rat liver were investigated. Due to the overlapping yet distinct substrate specificities of the hepatic glutathione S-transferases, we measured activity in cytosol toward four substrates: 1-chloro-2,4-dinitrobenzene, 1,2-dichloro-4-nitrobenzene, trans-4-phenylbut-3-en-2-one and p-nitrobenzyl chloride. Orchidectomy resulted in a decrease in transferase activity toward 1-chloro-2,4-dinitrobenzene, trans-4-phenylbut-3-en-2-one and p-nitrobenzyl chloride to 76, 64 and 70% of control. In contrast, transferase activity toward 1,2-dichloro-4-nitrobenzene was increased to 137% of control. To determine the role of specific androgens in the hormonal dependence of the glutathione S-transferases, rats were subcutaneously implanted for 4 weeks with either blank or steroid-filled sustained-release capsules at the time of orchidectomy. Transferase activities toward 1-chloro-2,4-dinitrobenzene or p-nitrobenzyl chloride were increased to control levels by testosterone but not by any of its 5α-reduced metabolites. Transferase activity toward trans-4-phenylbut-3-en-2-one was increased to control level by either dihydrotestosterone or 5α-androstan-3-α, 17β-diol. Activity toward 1,2-dichloro-4-nitrobenzene was decreased to control level by all of the androgens studied, testosterone, dihydrotestosterone, 5α-androstan-3β,17β-diol or 5α-androstan-3α,17β-diol. Thus, the hepatic glutathione S-transferases are under separate control and are differentially regulated by testosterone and its 5α-reduced metabolites.