UDP-GLUCURONOSYLTRANSFERASES IN HUMAN INTESTINAL-MUCOSA

Citation
A. Radominskapandya et al., UDP-GLUCURONOSYLTRANSFERASES IN HUMAN INTESTINAL-MUCOSA, Biochimica et biophysica acta, L. Lipids and lipid metabolism, 1394(2-3), 1998, pp. 199-208
Citations number
35
Categorie Soggetti
Biology,Biophysics
ISSN journal
00052760
Volume
1394
Issue
2-3
Year of publication
1998
Pages
199 - 208
Database
ISI
SICI code
0005-2760(1998)1394:2-3<199:UIHI>2.0.ZU;2-N
Abstract
While UDP-glucuronosyltransferases (UGTs) are known to be expressed at high levels in human liver, relatively little is known about extrahep atic expression. In the present study, UGT2B family isoforms involved in the glucuronidation of steroid hormones and bile acids have been ch aracterized in microsomes prepared from jejunum, ileum and colon from six human subjects. Glucuronidation of androsterone and testosterone w as 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 sig nificant 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 androste rone- and testosterone-UGT antibodies, whereas UGT2B4, a major hepatic hyodeoxycholic acid-specific UGT, was undetectable using a highly spe cific anti-human UGT2B4 antibody. Screening for RNA expression by RT-P CR 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 and rosterone and testosterone directed isoforms in human intestine is a n ovel finding which supports the idea that the intestinal tract functio ns as a steroid-metabolizing organ and plays a significant role in ste roid hormone biotransformation. (C) 1998 Published by Elsevier Science B.V. All rights reserved.