PT  - JOURNAL ARTICLE
AU  - Yuki Kutsuno
AU  - Rika Hirashima
AU  - Masaya Sakamoto
AU  - Hiroko Ushikubo
AU  - Hirofumi Michimae
AU  - Tomoo Itoh
AU  - Robert H Tukey
AU  - Ryoichi Fujiwara
TI  - Expression of UDP-Glucuronosyltransferase 1 (UGT1) and Glucuronidation Activity Toward Endogenous Substances in Humanized <em>UGT1</em> Mouse Brain
AID  - 10.1124/dmd.115.063719
DP  - 2015 May 07
TA  - Drug Metabolism and Disposition
PG  - dmd.115.063719
4099  - http://dmd.aspetjournals.org/content/early/2015/05/07/dmd.115.063719.short
4100  - http://dmd.aspetjournals.org/content/early/2015/05/07/dmd.115.063719.full
AB  - While UDP-glucuronosyltransferases (UGTs) are important phase II drug metabolizing enzymes, they are also involved in the metabolism of endogenous. Certain substrates of UGTs, such as serotonin and estradiol, play important roles in the brain. However, the expression of UGTs in human brain has not been fully clarified. Recently, humanized UGT1 mice (hUGT1 mice) in which the original Ugt1 locus was disrupted and replaced with the human UGT1 locus have been developed. In the present study, the expression pattern of UGT1As in brains from human and hUGT1 mice was examined. We found that UGT1A1, 1A3, 1A6, and 1A10 were expressed in human brains. The expression pattern of UGT1As in hUGT1 mouse brains was similar to that in human brains. In addition, we examined the expression of UGT1A1 and 1A6 in cerebellum, olfactory bulbs, midbrain, hippocampus, and cerebral cortex of hUGT1 mice. UGT1A1 in all brain regions and UGT1A6 in cerebellum and cerebral cortex of 6 month-old hUGT1 mice were expressed significantly higher than those of 2 week-old hUGT1 mice. A difference in expression levels between brain regions was also observed. Brain microsomes exhibited glucuronidation activities toward estradiol and serotonin with the mean values of 0.13 pmol/min/mg and 5.17 pmol/min/mg, respectively. In conclusion, UGT1A1 and UGT1A6 might play important role in function regulation of endogenous compounds in region- and age-dependent manner. Humanized UGT1 mice might be useful to study the importance of brain UGTs in vivo.