UDP-glucuronosyltransferases in human intestinal mucosa
UDP-glucuronosyltransferases in human intestinal mucosa
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DOI：
10.1016/s0005-2760(98)00115-5
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发表时间：
1998-11-02
期刊：
影响因子：
--
通讯作者：
Raufman, JP
中科院分区：
文献类型：
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作者：
Radominska-Pandya, A;Little, JM;Raufman, JP
虽然UDP-葡萄糖醛酸基转移酶（UGT）已知在人类肝脏中以高水平表达，但对肝外表达知之甚少。在本研究中，已在从6名人类受试者的空肠、回肠和结肠制备的微粒体中表征了参与类固醇激素和胆汁酸葡萄糖醛酸化的UGT 2B家族亚型。雄酮和睾酮的葡萄糖醛酸化非常显著，并且从近端到远端肠增加。相比之下，猪去氧胆酸在空肠和回肠中的葡萄糖醛酸化水平较低，在结肠中几乎检测不到活性。未发现石胆酸的显著葡萄糖醛酸化，小分子酚的葡萄糖醛酸化活性远低于肝脏中的活性。使用多克隆抗大鼠雄酮和睾酮UGT抗体检测到高水平的UGT蛋白，而使用高度特异性抗人UGT 2B 4抗体检测不到UGT 2B 4（一种主要的肝猪去氧胆酸特异性UGT）。通过RT-PCR筛选RNA表达证实了不存在UGT 2B 4和UGT 1A 6，并显示在所有肠段中表达UGT 2B 7，UGT 2B 7是一种显示为葡萄糖醛酸化雄酮的肝脏亚型。据我们所知，在人类肠道中存在功能性雄酮和睾酮定向异构体是一个新的发现，这支持了肠道作为类固醇代谢器官发挥功能并在类固醇激素生物转化中起重要作用的观点。(C)1998年由Elsevier Science B. V.出版，版权所有。
While UDP-glucuronosyltransferases (UGTs) are known to be expressed at high levels in human liver, relatively little is known about extrahepatic expression. In the present study, UGT2B family isoforms involved in the glucuronidation of steroid hormones and bile acids have been characterized in microsomes prepared from jejunum, ileum and colon from six human subjects. Glucuronidation of androsterone and testosterone was highly significant and increased from proximal to distal intestine. In contrast, hyodeoxycholic acid was glucuronidated at a low level in jejunum and ileum and activity was barely detectable in colon. No significant glucuronidation of lithocholic acid was found. Small phenols were glucuronidated with much lower activity than found in liver. High levels of UGT protein were detected with polyclonal anti-rat androsterone- and testosterone-UGT antibodies, whereas UGT2B4, a major hepatic hyodeoxycholic acid-specific UGT, was undetectable using a highly specific anti-human UGT2B4 antibody. Screening for RNA expression by RT-PCR confirmed the absence of UGT2B4 and UGT1A6 and showed expression of UGT2B7, a hepatic isoform shown to glucuronidate androsterone, in all intestinal segments. To our knowledge, the presence of functional androsterone and testosterone directed isoforms in human intestine is a novel finding which supports the idea that the intestinal tract functions as a steroid-metabolizing organ and plays a significant role in steroid hormone biotransformation. (C) 1998 Published by Elsevier Science B.V. All rights reserved.