Effects of chronic ethanol on growth hormone secretion and hepatic cytochrome P450 isozymes of the rat.
Growth hormone (GH) secretion is sexually dimorphic in the laboratory rat and the plasma GH profile is a determining factor in the regulation of the male-specific cytochrome P450 (CYP) 2C11. Acute ethanol has been reported previously to alter the secretion of GH, and in the present investigation, we have studied the effects of chronic (38 days) ethanol on plasma GH profiles, CYP 2C11 and the major ethanol-inducible cytochrome, CYP 2E1, using a total enteral nutrition system, where 35% of the total calories were ethanol. Ethanol-treated rats had elevated (P < or = .05) CYP 2E1 activities and apoprotein levels and increased steady-state mRNA levels encoding for CYP 2E1. Ethanol-treated rats also had reduced (P < or = .05) hydroxylation of testosterone at positions 2 alpha and 16 alpha, lower 2C11 apoprotein levels and lower steady-state mRNA levels encoding for 2C11. In addition, the plasma GH pulse profiles were altered in chronically treated rats by reducing (P < or = .05) the GH pulse amplitude and mean plasma GH concentrations. Our results suggest that: 1) the reduced CYP 2C11 activities, apoprotein levels and steady-state mRNA levels during chronic alcohol exposure are causally related to the alterations in GH secretion; and 2) chronic alcohol exposure elevated CYP 2E1 activities, apoprotein levels and steady-state mRNA levels, and these changes occurred primarily as the result of ethanol rather than undernutrition or as the combination of ethanol and undernutrition.
Badger
T M
TM
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock.
Ronis
M J
MJ
Lumpkin
C K
CK
Valentine
C R
CR
Shahare
M
M
Irby
D
D
Huang
J
J
Mercado
C
C
Thomas
P
P
Ingelman-Sundberg
M
M
D000728:Androgens / Q000378:metabolism; D000818:Animals; D001059:Apoproteins / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases; D001835:Body Weight / Q000187:drug effects; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D004032:Diet; D004790:Enzyme Induction; D000431:Ethanol / Q000494:pharmacology*; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D007527:Isoenzymes / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D010089:Oxidoreductases, N-Demethylating / Q000187:drug effects / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism; D010288:Parenteral Nutrition; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000187:drug effects / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D013997:Time Factors
D000728:Androgens; D001059:Apoproteins; D007527:Isoenzymes; D012333:RNA, Messenger; D000431:Ethanol; D013739:Testosterone; D013006:Growth Hormone; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D013250:Steroid Hydroxylases; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; D039181:Steroid 16-alpha-Hydroxylase; D010089:Oxidoreductases, N-Demethylating