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苯巴比妥诱导的肝细胞色素P450 2B1和2B2的生长激素依赖性和非依赖性性别二态性调节

Growth hormone-dependent and -independent sexually dimorphic regulation of phenobarbital-induced hepatic cytochromes P450 2B1 and 2B2.

作者信息

Shapiro B H, Pampori N A, Lapenson D P, Waxman D J

机构信息

Laboratories of Biochemistry, University of Pennsylvania School of Veterinary Medicine, Philadelphia 19104-6048.

出版信息

Arch Biochem Biophys. 1994 Jul;312(1):234-9. doi: 10.1006/abbi.1994.1304.

DOI:10.1006/abbi.1994.1304
PMID:8031133
Abstract

Sexually dimorphic regulation of phenobarbital-induced cytochromes P450 2B1 and 2B2 (collectively referred to as P450 2B) as well as P450 2B-dependent monooxygenase activities was studied in multi-hormone-depleted hypophysectomized rats and in growth hormone (GH)-deficient monosodium glutamate (MSG)-treated rats. Our results indicate that endogenous GH suppresses phenobarbital induction of P450 2B and that the feminine pattern of continuous GH secretion is more suppressive than the masculine profile of episodic secretion. Moreover, we have found that it is the height of the GH pulse, and not necessarily its frequency nor the interpulse trough periods, that signals the suppressive effects of GH on P450 2B expression in male rats. Last, irrespective of the presence or absence of circulating GH, the magnitude of phenobarbital induction of P450 2B and associated monooxygenases was consistently lower in female rats, suggesting the presence of some degree of sex-dependent, but GH-independent regulation.

摘要

在多激素耗竭的垂体切除大鼠以及生长激素(GH)缺乏的谷氨酸单钠(MSG)处理大鼠中,研究了苯巴比妥诱导的细胞色素P450 2B1和2B2(统称为P450 2B)的性别二态性调节以及P450 2B依赖性单加氧酶活性。我们的结果表明,内源性GH抑制苯巴比妥对P450 2B的诱导,并且持续GH分泌的女性模式比间歇性分泌的男性模式更具抑制性。此外,我们发现是GH脉冲的峰值,而不一定是其频率或脉冲间期低谷期,表明GH对雄性大鼠P450 2B表达具有抑制作用。最后,无论循环GH是否存在,雌性大鼠中苯巴比妥诱导P450 2B及相关单加氧酶的幅度始终较低,这表明存在某种程度的性别依赖性但GH非依赖性调节。

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