Regulation of the mouse liver cytochrome P450 2B subfamily by sex hormones and phenobarbital
| Autor: | Paavo Honkakoski, Anneli Kojo, Matti A. Lang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1992 |
| Předmět: |
Male
medicine.medical_specialty Subfamily Ovariectomy Molecular Sequence Data Biology Biochemistry Isozyme Mice Cytochrome P-450 Enzyme System Internal medicine Gene expression medicine Animals Testosterone Amino Acid Sequence RNA Messenger Gonadal Steroid Hormones Molecular Biology Messenger RNA Mice Inbred BALB C Sex Characteristics Estradiol Chromosome localization Cytochrome P450 Cell Biology Molecular biology Endocrinology Gene Expression Regulation Liver Steroid 16-alpha-Hydroxylase Mice Inbred DBA Enzyme Induction Phenobarbital biology.protein Female Orchiectomy medicine.drug Hormone Research Article |
| Popis: | The sex-dependent expression and inducibility of the cytochrome P450 2B subfamily was studied in DBA/2 and Balb/c mice, and their F1 recombinants, at the mRNA, protein and activity levels. Analysis of poly(A)+ RNA with specific oligonucleotide probes directed to known mRNAs within the mouse 2B subfamily revealed that the levels of P450 2b-10 and 2b-9 mRNAs were co-regulated with two proteins (56 and 53 kDa) detected by a 2B-specific polyclonal antibody. Other mRNAs related to the 2B subfamily were barely or not at all detectable, and did not coincide with protein expression, suggesting that P450s 2b-9 and 2b-10 are the major 2B isoenzymes present in mouse liver. Specifically, castration of males increased the expression of 2b-9 and 2b-10 mRNAs and protein up to female levels, and testosterone administration to castrated mice reversed these changes. Ovariectomy of females appears to increase the expression of these P450s slightly. 2b-10, but not 2b-9, mRNA and protein were induced by phenobarbital. Based on immunoinhibition studies and the levels of these isoenzymes, P4502b-10 appears to be the major catalyst of 7-pentoxyresorufin O-dealkylation. Both P4502b-9 and P4502b-10 contribute up to 30% of the testosterone 16 alpha-hydroxylation, the balance being catalysed by P450s within the 2D subfamily. These experiments show that the female-predominant expression of the two mouse liver isoenzymes P4502b-9 and P4502b-10 is dependent on sex hormones. The fact that P4502b-9 does not respond to phenobarbital, while P4502b-10 is regulated by both phenobarbital and sex hormones, demonstrates the complexity of P450 expression even within one subfamily. |
| Databáze: | OpenAIRE |
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