人肠黏膜udp -葡萄糖醛酸转移酶

Anna Radominska-Pandya , Joanna M. Little , Jay T. Pandya , Thomas R. Tephly , Christopher D. King , Gary W. Barone , Jean-Pierre Raufman
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引用次数: 120

摘要

虽然已知udp -葡萄糖醛酸转移酶(UGTs)在人肝脏中高水平表达,但对肝外表达的了解相对较少。在本研究中,参与类固醇激素和胆汁酸糖醛酸化的UGT2B家族异构体在6人的空肠、回肠和结肠制备的微粒体中被表征。雄酮和睾酮的糖醛酸化非常显著,且从近端到远端逐渐增加。相反,羟脱氧胆酸在空肠和回肠中葡萄糖醛酸化水平较低,在结肠中几乎检测不到活性。石胆酸未见明显葡萄糖醛酸化。小酚被葡萄糖醛酸化,活性比肝脏低得多。多克隆抗大鼠雄酮和睾酮UGT抗体检测到高水平的UGT蛋白,而高特异性的抗人UGT2B4抗体检测不到UGT2B4, UGT2B4是一种主要的肝羟脱氧胆酸特异性UGT。通过RT-PCR筛选RNA表达,证实UGT2B4和UGT1A6缺失,UGT2B7(一种显示葡萄糖醛酸雄酮的肝脏异构体)在所有肠段均有表达。据我们所知,人类肠道中功能性雄酮和睾酮定向异构体的存在是一项新发现,它支持了肠道作为类固醇代谢器官并在类固醇激素生物转化中发挥重要作用的观点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
UDP-glucuronosyltransferases in human intestinal mucosa

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.

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