Roles of pituitary hormones in the regulation of hepatic cytochrome P450IIE1 in rats and mice
| Autor: | Shu M. Ning, Jinmei Pan, Chung S. Yang, Bing-Li Ma, M. J. Lee, Jun-Yan Hong |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
medicine.medical_specialty
Hypophysectomy Ratón medicine.medical_treatment Biophysics Ketone Bodies Biochemistry Acetone Mice Species Specificity Internal medicine medicine Animals RNA Messenger Molecular Biology NADPH-Ferrihemoprotein Reductase chemistry.chemical_classification Mice Inbred BALB C biology Cytochrome P450 Cytochrome P-450 CYP2E1 Oxidoreductases N-Demethylating Rats Inbred Strains Fasting biology.organism_classification Enzyme assay Rats Pituitary Hormones Endocrinology Enzyme Microsoma chemistry Enzyme Induction Ketone bodies Microsome biology.protein Microsomes Liver |
| Zdroj: | Archives of biochemistry and biophysics. 281(1) |
| ISSN: | 0003-9861 |
| Popis: | Cytochrome P450IIE1 (P450IIE1) is responsible for the metabolic activation of N -nitrosodimethylamine (NDMA), a potent environmental carcinogen. This P450 enzyme displays a high-affinity NDMA demethylase (NDMAd) activity and is known to be induced by fasting and acetone administration. In the present work, the effects of pituitary hormones on the regulation of P450IIE1 in the liver were investigated and compared in rats and mice. There was no difference in liver microsomal NDMAd activity (nmol/min/mg protein) in rats in the intact (0.38 ± 0.12), sham-operated (0.44 ± 0.06), and hypophysectomized (0.52 ± 0.04) groups. However, hypophysectomy caused a 2-fold increase in hepatic P450IIE1 protein levels as determined by immunoblot analysis. The P450IIE1 mRNA level in hypophysectomized rat was also significantly increased. The levels of blood ketone bodies (acetone, acetoacetate, and β-hydroxybutyrate) were not different in the intact, sham-operated, and hypophysectomized groups, suggesting that ketone bodies are not involved in the induction of P450IIE1 protein and its mRNA by hypophysectomy. The discrepancy between the NDMAd activity and the increased P450IIE1 protein in rat liver by hypophysectomy can be partially explained by the lower hepatic NADPH-P450 reductase activity (50% that of the control) in the hypophysectomized rats. Upon the induction of liver NDMAd activity by fasting and acetone, hypophysectomy attenuated the effect of acetone but abolished the effect of fasting completely. Nevertheless, fasting still caused a 3-fold increase in the liver P450IIE1 mRNA level. An involvement of pituitary hormones in the regulation of liver microsomal P450IIE1 in mouse, however, was not observed. There was no difference in constitutive NDMAd activity between genetically growth hormone-deficient ( lit/lit ) mice and their phenotypically normal heterozygotes ( lit /+). Fasting for 48 h caused 1.5- to 2-fold induction and acetone caused 2- to 3-fold induction, in both groups. The above changes in enzyme activity were due to the changes of P450IIE1 levels as verified by the immunoblot analysis. In male BALB/c mice, neither the hepatic NDMAd activity nor the P450IIE1 protein level was altered by hypophysectomy. The effects of acetone on the liver NDMAd activity were also similar in hypophysectomized and sham-operated mice. The results suggest that pituitary hormones are important in the regulation of the expression and activity of hepatic P450IIE1 in rats but not in the mouse strains investigated. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|