Radominska-Pandya A, Little J M, Pandya J T, Tephly T R, King C D, Barone G W, Raufman J P
Division of Gastroenterology, Department of Internal Medicine, Department of Surgery, University of Arkansas for Medical Sciences, 4301 W. Markham, Slot 567, Little Rock, AR, USA.
Biochim Biophys Acta. 1998 Nov 2;1394(2-3):199-208. doi: 10.1016/s0005-2760(98)00115-5.
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.
虽然已知尿苷二磷酸葡萄糖醛酸基转移酶（UGTs）在人类肝脏中高水平表达，但关于其肝外表达的了解相对较少。在本研究中，对参与类固醇激素和胆汁酸葡萄糖醛酸化的UGT2B家族同工型在六名人类受试者空肠、回肠和结肠制备的微粒体中进行了表征。雄甾酮和睾酮的葡萄糖醛酸化非常显著，且从近端肠道到远端肠道呈增加趋势。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。未发现石胆酸有显著的葡萄糖醛酸化。小分子酚类的葡萄糖醛酸化活性远低于肝脏中的活性。用多克隆抗大鼠雄甾酮和睾酮UGT抗体检测到高水平的UGT蛋白，而使用高度特异性的抗人UGT2B4抗体未检测到主要的肝脏猪去氧胆酸特异性UGT即UGT2B4。通过逆转录聚合酶链反应（RT-PCR）筛选RNA表达证实UGT2B4和UGT1A6不存在，并显示UGT2B7（一种已证明可使雄甾酮葡萄糖醛酸化的肝脏同工型）在所有肠段均有表达。据我们所知，人类肠道中存在功能性的雄甾酮和睾酮导向的同工型是一项新发现，这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起重要作用的观点。
