UGT1 family expression in human gastrointestinal tissues by in situ hybridisation

Glucuronide conjugation catalysed by UGT I enzymes is an important determinant of response to xenobiotics and endogenous toxins. Regulation of the human UGTI locus is tissue specific with unique expression of multiple hepatic and extrahepatic enzymes. To precisely define the spatial pattern of UGTI expression in human esophagus and colon, we performed in situ hybridisation analysis using riboprobes transcribed from exon I of UGTIAI, UGTIA3, UGTIA6 and UGTIAIO. The lAl riboprobe is specific for lAl mRNA, the 1A3 probe detects 1A3, 1A4 and 1A5, the 1A6 probe is specific for 1A6 and the lAIO probe detects 1A7, 1A8, 1A9, lAIO. All riboprobes detect UGT mRNA in human colon, with signal predominantly localized to basal cells in the crypts of the colon. UGT mRNA was detected in the surface epithelium of the colon but at reduced levels. All four UGT riboprobes also detected mRNA in the human esophagus, localized to the squamous epithelium. Whereas the basal and paraba-sal cells stain positively for UGT mRNA, more mature cells in the esophagus do not exhibit positive staining. The spatial pattern of UGT expression evident in the present studies is suggestive of a role for UGTI enzymes in the gastrointestinal tract other than xenobiotic detoxification.