Serum acetone and liver acetone monooxygenase activity in pregnant rats, fetuses, and neonates: reversible pretranslational reduction of cytochrome P450IIE1 (P450IIE1) during pregnancy.
Serum acetone in neonates was found to increase from < 20 microM at 20 days gestation to 377 +/- 107 microM 1 day after birth. This increase in acetone occurs concurrently with the initial expression of liver P450IIE1 in rat (Song et al., 1986, J. Biol. Chem. 261:16689-16697). Treating pregnant rats with drinking water containing 1% acetone did not result in a premature induction of liver acetone monooxygenase, a P450IIE1 catalyzed activity, in fetuses sacrificed at 20 days gestation. The data indicate that increased serum acetone levels are not responsible for the initial induction of P450IIE1 in neonates. However, acetone monooxygenase activity in their mothers was significantly less than acetone-treated females which were not pregnant, indicating a reduced activity of P450IIE1 during pregnancy although its induction by acetone was still observed. Acetone monooxygenase activity in 20 day pregnant rats given untreated drinking water was also less than in nongravid rats. These findings are supported by immunoblot data which show significant and progressive reductions in liver P450IIE1 in both untreated and acetone-treated rats during pregnancy. Northern mRNA blot analysis further revealed that the decreases in P450IIE1 activity and protein content were mainly due to pretranslational suppression with reduced level of its mRNA. However, their levels rapidly returned to the control level after parturition (within 1 day). Repeated administration of several exogenous hormones (estriol, pregnanediol, thyroxine) or peptide hormones (placental lactogen, prolactin, chorionic gonadotropin) failed to suppress P450IIE1 in nonpregnant rats, indicating a possibility of another factor(s) responsible for the P450IIE1 suppression during pregnancy.
Casazza
J P
JP
Laboratory of Metabolism, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20852.
Sohn
D H
DH
Park
K S
KS
Song
B J
BJ
D000096:Acetone / Q000097:blood*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D015152:Blotting, Northern; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004790:Enzyme Induction; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006133:Growth Substances / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology; D008099:Liver / Q000196:embryology / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D006133:Growth Substances; D006728:Hormones; D012333:RNA, Messenger; D000096:Acetone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019392:Cytochrome P-450 CYP2E1; C045704:acetone monooxygenase; D010089:Oxidoreductases, N-Demethylating