Hormonal regulation of microsomal cytochrome P4502E1 and P450 reductase inrat liver and kidney

1. The relative roles of pituitary hormones (especially growth hormone) and testicular hormones (especially testosterone) in the regulation of renal a nd hepatic CYP2E1 and cytochrome P450 reductase have been studied in the ma le rat. 2. Depletion of pituitary hormones by hypophysectomy (Hx) resulted in 12-14 -fold increases in renal CYP2E1 (P less than or equal to 0.05) and a 40% dr op in NADPH-dependent cytochrome c reductase activity (p less than or equal to 0.05) compared with 6-fold increases in CYP2E1 (p less than or equal to 0.05) and a 60% drop in P450 reductase apoprotein (p less than or equal to 0.05) in the liver. 3. The increase in hepatic CYP2E1 was associated with increased gene transc ription in nuclear run-on experiments. 4. Restoration of renal CYP2E1 to control levels by hormone treatment requi red both growth hormone and an intact testis, whereas partial restoration o f CYP2E1 apoprotein levels in liver was accomplished by growth hormone, but not testosterone. 5. Renal NADPH-dependent cytochrome c reductase activity was restored by gr owth hormone and testosterone treatment, whereas the hepatic reductase appe ared to be regulated by other pituitary hormones. 6. CYP2E1 and P450 reductase appear to be under complex endocrine regulatio n by pituitary and testicular hormones in a tissue specific manner.