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长期胆碱缺乏对雌性大鼠肝脏微粒体细胞色素P-450介导的类固醇和外源性物质羟化酶的影响。

Effects of long-term choline deficiency on hepatic microsomal cytochrome P-450-mediated steroid and xenobiotic hydroxylases in the female rat.

作者信息

Murray M, Cantrill E, Frost L, Mehta I, Farrell G C

机构信息

Department of Medicine, University of Sydney, Westmead Hospital, N.S.W., Australia.

出版信息

Biochem Pharmacol. 1988 Apr 1;37(7):1187-92. doi: 10.1016/0006-2952(88)90769-1.

DOI:10.1016/0006-2952(88)90769-1
PMID:3355592
Abstract

Total cytochrome P-450 levels decreased to about 80% of control in hepatic microsomes from female rats maintained for 30 weeks on a choline-deficient diet. Livers from these rats were fibrotic and had extensive fatty infiltration but, unlike livers of male rats on the same regimen, were not cirrhotic. Steroid hydroxylase activities were assessed in microsomes of female rats that received the choline-deficient diet and it was noted that the activity of the cytochrome P-450 UT-F-mediated steroid 7 alpha-hydroxylase was decreased to about 50% of the activity present in choline-supplemented control rat microsomes. Similar decreases were observed for microsomal androstenedione 6 beta-hydroxylase and aniline 4-hydroxylase activities. In female rat hepatic microsomes these two activities are probably mediated by the isozyme cytochrome P-450 ISF-G. In contrast to these findings, the activities of four other xenobiotic metabolising enzymes, as well as rates of microsomal steroid 16 alpha- and 16 beta-hydroxylation, were unchanged from control. Thus, in hepatic microsomes from choline-deficient female rats, it appears likely that levels of the non-sexually differentiated cytochromes P-450 UT-F and ISF-G are decreased. Unlike the situation in male rats, long term choline deficiency does not appear to influence levels of sexually-differentiated P-450 enzymes in the female rat.

摘要

在胆碱缺乏饮食中维持30周的雌性大鼠肝脏微粒体中,细胞色素P-450的总水平降至对照的约80%。这些大鼠的肝脏出现纤维化并伴有广泛的脂肪浸润,但与接受相同饮食方案的雄性大鼠肝脏不同,未出现肝硬化。对接受胆碱缺乏饮食的雌性大鼠微粒体中的类固醇羟化酶活性进行了评估,结果发现细胞色素P-450 UT-F介导的类固醇7α-羟化酶活性降至补充胆碱的对照大鼠微粒体中活性的约50%。微粒体雄烯二酮6β-羟化酶和苯胺4-羟化酶活性也出现了类似程度的下降。在雌性大鼠肝脏微粒体中,这两种活性可能由细胞色素P-450 ISF-G同工酶介导。与这些发现相反,其他四种外源化合物代谢酶的活性以及微粒体类固醇16α-和16β-羟化率与对照相比没有变化。因此,在胆碱缺乏的雌性大鼠肝脏微粒体中,非性别分化的细胞色素P-450 UT-F和ISF-G的水平似乎降低了。与雄性大鼠的情况不同,长期胆碱缺乏似乎不会影响雌性大鼠中性别分化的P-450酶的水平。

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