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First published on October 6, 2008; DOI: 10.1124/dmd.108.023598

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Received for publication July 28, 2008.
Revised September 29, 2008.
Accepted for publication October 3, 2008.

Determination of mRNA expression of human UGTs and application for localization in various human tissues by real time RT-PCR

Shuji Ohno 1* Shizuo Nakajin 2

1 Hoshi University 2 Hoshi University School of pharmacy and Pharmaceitical Sciences

* Address correspondence to: E-mail: ohno{at}hoshi.ac.jp

Abstract

An exhaustive real time RT-PCR quantification method was used to determine 15 of the catalytically active human uridine diphospho-glucuronosyltransferase (UGT) isoforms (1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B10, 2B11, 2B15, and 2B17). The specific primers for respective human UGTs were developed for differential determination. The cDNA derived from the 1A7 isoform was detected in the esophagus, the 1A8 and 1A10 isoforms were detected in the small intestine and all other isoforms were detected in at least the liver by PCR. In all cases, single bands of the expected size on the agarose gel were confirmed to correspond with the predicted UGT isoform sequences. Each calibration curve showed linearity between the PCR crossing point and the calibrator copy number. The correlation coefficients were greater than 0.9957 with high reproducibility. This exhaustive measurement method was applied to UGT expression in 23 human tissue types. UGT was mostly expressed in the alimentary system and liver. Surprisingly, extremely high expression in the liver was found for UGT2B4 and 2B15, which had respectively 8.98 and 4.38 times greater expression than UGT2B7 in the liver. In addition, even though expressed at low levels, several UGT isoforms were expressed in steroidogenic tissues, such as the breast, prostate, heart and adrenal. Therefore, this quantification method may provide valuable information about the medical efficacy or pharmacokinetic characteristics of a wide variety of UGT-metabolized drugs.


Key words: distribution, UDP glucuronyltransferases


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