Hormonal regulation of microsomal cytochrome P4502E1 and P450 reductase in rat liver and kidney.
1. The relative roles of pituitary hormones (especially growth hormone) and testicular hormones (especially testosterone) in the regulation of renal and hepatic CYP2E1 and cytochrome P450 reductase have been studied in the male rat. 2. Depletion of pituitary hormones by hypophysectomy (Hx) resulted in 12-14-fold increases in renal CYP2E1 (p < or = 0.05) and a 40% drop in NADPH-dependent cytochrome c reductase activity (p < or = 0.05) compared with 6-fold increases in CYP2E1 (p < or = 0.05) and a 60% drop in P450 reductase apoprotein (p < or = 0.05) in the liver. 3. The increase in hepatic CYP2E1 was associated with increased gene transcription in nuclear run-on experiments. 4. Restoration of renal CYP2E1 to control levels by hormone treatment required both growth hormone and an intact testis, whereas partial restoration of CYP2E1 apoprotein levels in liver was accomplished by growth hormone, but not testosterone. 5. Renal NADPH-dependent cytochrome c reductase activity was restored by growth hormone and testosterone treatment, whereas the hepatic reductase appeared to be regulated by other pituitary hormones. 6. CYP2E1 and P450 reductase appear to be under complex endocrine regulation by pituitary and testicular hormones in a tissue specific manner.
Chen
G F
GF
Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock 72205, USA.
Ronis
M J
MJ
Ingelman-Sundberg
M
M
Badger
T M
TM
D000728:Androgens / Q000378:metabolism; D000818:Animals; D019392:Cytochrome P-450 CYP2E1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013006:Growth Hormone / Q000378:metabolism / Q000494:pharmacology; D006728:Hormones / Q000378:metabolism* / Q000494:pharmacology; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000187:drug effects / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase; D009919:Orchiectomy; D010902:Pituitary Gland / Q000502:physiology / Q000601:surgery; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000097:blood; D014158:Transcription, Genetic; D015430:Weight Gain / Q000187:drug effects
D000728:Androgens; D006728:Hormones; D012333:RNA, Messenger; D013739:Testosterone; D009249:NADP; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D019392:Cytochrome P-450 CYP2E1; D009247:NADH, NADPH Oxidoreductases; D009251:NADPH-Ferrihemoprotein Reductase