Effects of pregnant mare serum gonadotrophin and oestradiol benzoate on enzymes associated with xenobiotic metabolism in immature and hypophysectomized female rats.

Treatment of immature (22-day-old) female Sprague-Dawley rats with pregnant mare serum gonadotrophin (PMSG) resulted in a significant increase in hepatic microsomal cytochrome P-450 concentrations when compared with animals treated with 0.9% (w/v) NaCl solution. Cytochrome P-450 concentrations in microsomes from control and PMSG-treated animals were 0.49 +/- 0.07 and 0.78 +/- 0.18 nmol/mg microsomal protein respectively (mean +/- S.D.). When hypophysectomized rats were treated with PMSG no significant difference was observed between saline-treated and PMSG-treated animals (0.84 +/- 0.06 vs 0.88 +/- 0.08 nmol/mg microsomal protein). Cytochrome b5 concentration and NADPH-cytochrome c reductase and ferricyanide reductase activities were not significantly affected by PMSG treatment. Similar results were obtained when immature and hypophysectomized rats were treated with oestradiol benzoate. Hepatic glutathione (GSH) S-transferase activity was significantly stimulated over control values when hypophysectomized or immature animals were treated with PMSG, oestradiol benzoate or 3-methylcholanthrene. Treatment of animals simultaneously with PMSG or oestradiol benzoate and 3-methylcholanthrene resulted in higher transferase activity than did either treatment alone. Oestradiol benzoate or PMSG treatment of immature female rats resulted in an approximate twofold increase in hepatic aryl hydrocarbon hydroxylase (AHH) activity. However, AHH activity in hypophysectomized animals was not significantly increased by PMSG or oestradiol benzoate treatment. It is concluded that PMSG or oestradiol benzoate treatment of immature female rats resulted in increased total cytochrome P-450 concentration and AHH activity in hepatic microsomes. Glutathione S-transferase activity was also stimulated. Neither PMSG nor oestradiol benzoate stimulated cytochrome P-450 levels or AHH activity in hypophysectomized rats.(ABSTRACT TRUNCATED AT 250 WORDS)