Tissue-specific constitutive and inducible expression of rat phenol UDP-glucuronosyltransferase.
To investigate constitutive and inducible expression of rat phenol UDP-glucuronosyltransferase (UGT1A1) in liver and extrahepatic tissues, a selective cDNA probe for its unique exon 1 was utilized. 6-Hydroxychrysene was used as a functional probe of UGT1A1 activity. Constitutive expression of UGT1A1 was low in liver, but high in kidney, testis, epididymis and ovary. After treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 10 micrograms/kg for 7 days) the UGT1A1 mRNA level was markedly increased in liver (ca. 10-fold), and only moderately enhanced (up to 2-fold) in extrahepatic tissues where constitutive enzyme expression was high. UGT activity toward 6-hydroxychrysene was strongly inducible in liver (ca. 9-fold) and only moderately inducible in extrahepatic tissues (up to 2-fold). The results suggest complex tissue-specific regulation of UGT1A1 including positive and negative transcriptional factors and marked inducibility by TCDD in liver.
Münzel
P A
PA
Institute of Toxicology, University of Tübingen, Germany.
Brück
M
M
Bock
K W
KW
D000818:Animals; D002911:Chrysenes / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D002911:Chrysenes; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; C087203:6-hydroxychrysene; D014453:Glucuronosyltransferase