REGULATION OF RAT HEPATIC CYTOCHROME-P-450 - AGE-DEPENDENT EXPRESSION, HORMONAL IMPRINTING, AND XENOBIOTIC INDUCIBILITY OF SEX-SPECIFIC ISOENZYMES
REGULATION OF RAT HEPATIC CYTOCHROME-P-450 - AGE-DEPENDENT EXPRESSION, HORMONAL IMPRINTING, AND XENOBIOTIC INDUCIBILITY OF SEX-SPECIFIC ISOENZYMES
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DOI：
10.1021/bi00337a023
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发表时间：
1985-01-01
期刊：
影响因子：
2.9
通讯作者：
GUENGERICH, FP
中科院分区：
文献类型：
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作者：
WAXMAN, DJ;DANNAN, GA;GUENGERICH, FP
采用催化和免疫化学方法研究了年龄、性别和激素水平对8种大鼠肝细胞色素P-450 （P-450）同工酶表达的影响。p - 4502c的雄性特异性。/UT-A，主要微粒体类固醇16。非诱导大鼠肝脏-羟化酶[Waxman， D.J.(1984)]反映了其。在雄性大鼠的青春期有30倍的诱导作用，而雌性大鼠没有。P-450 2d的女性特异性（.female.）/ ut - 1在雌性中反映了其发育诱导作用。P-450 PB-2a/PCN-E介导。gtoreq。85%微粒体类固醇6 -。羟化酶活动;该P-450的雄性特异性在很大程度上反映了其在雌性大鼠中的发育抑制作用。新生儿性腺切除术和激素替代实验证实，新生儿雄激素印记或程序雄性大鼠发育诱导P-450 2c。/UT-A，用于维持P-450 PB-2a/PCN-E，并抑制P-450 2d（.雌性）。/ ut - 1，所有这些都发生在青春期的雄性大鼠身上。P-450同工酶PB-1/PB-C、3/UT-F、PB-4/PB-B、ISF-G和。β的表达水平。NF-B基本上不受大鼠年龄、性别和荷尔蒙状况的影响。对P-450诱导的性别特异性研究表明，后5种同工酶对P-450诱导剂苯巴比妥、β。-napthoflavone,孕烯醇酮- 16. -α。-碳腈和异黄樟醇在女性和男性体内的质量和数量是相同的。虽然这些药物都没有诱导P-450 2d（雌性）。/ ut - 1在男性或诱导P-45- 2c（.男性）。/UT-A在女性中，孕烯素-16。-碳腈管理导致了一个。在雌性大鼠肝脏中70倍诱导P-450 PB-2a/PCN-E，从而消除这种类固醇6. β的性别特异性表达。羟化酶p - 450。参与外源化合物代谢的多种大鼠肝脏P-450活性受到生理因素的独立调节，进一步揭示了外源化合物暴露对P-450催化的大鼠肝组织类固醇激素羟基化的复杂影响。
The influence of age, sex and hormonal status on the expression of 8 rat hepatic cytochrome P-450 (P-450) isoenzymes was evaluated by both catalytic and immunochemical methods. The male specificity of P-450 2c .male./UT-A, the major microsomal steroid 16.alpha.-hydroxylase of uninduced rat liver [Waxman, D.J. (1984)] was shown to reflect its .gtoreq. 30-fold induction at puberty in male but not in female rats. The female specificity of P-450 2d (.female.)/UT-I was shown to reflect its developmental induction in females. P-450 PB-2a/PCN-E was shown to mediate .gtoreq. 85% of microsomal steroid 6.beta.-hydroxylase activity; the male specificity of this P-450 largely reflects its developmental suppression in female rats. Neonatal gonadectomy and hormonal replacement experiments established that neonatal androgen imprints or programs the male rat for developmental induction of P-450 2c (.male.)/UT-A, for maintenance of P-450 PB-2a/PCN-E, and for suppression of P-450 2d (.female.)/UT-I, all of which occur in male rats at puberty. The expressed levels of P-450 isoenzymes PB-1/PB-C, 3/UT-F, PB-4/PB-B, ISF-G, and .beta.NF-B were mostly unaffected by the rats'' age, sex and hormonal status. Studies on the sex specificity of P-450 induction established that the response of these latter 5 isoenzymes to the P-450 inducers phenobarbital, .beta.-napthoflavone, pregnenolone-16.alpha.-carbonitrile, and isosafrole is qualitatively and quantitatively equivalent in females as in males. Although none of these agents effected an induction of P-450 2d (.female.)/UT-I in males or an induction of P-45- 2c (.male.)/UT-A in females, pregnenoline-16.alpha.-carbonitrile administration led to a .gtoreq. 70-fold induction of P-450 PB-2a/PCN-E in female rat liver, thereby abolishing the sex-specific expression of this steroid 6.beta.-hydroxylase P-450. The multiple rat liver P-450 active in foreign compound metabolism are independently regulated by physiological factors and further serve to highlight the complex influences of foreign compound exposure on P-450-catalyzed steroid hormone hydroxylations in rat hepatic tissue.