The monkey and human uridine diphosphate-glucuronosyltransferase UGT1A9, expressed in steroid target tissues, are estrogen-conjugating enzymes

Considering the physiologic importance of the steroid response, which is re gulated in part by steroid levels in a given tissue, relatively little is k nown about steroid glucuronidation, which is widely accepted as a major pat hway involved in the catabolism and elimination of steroid hormones from th e human body. In a previous study, it was ascertained that the monkey may b e the most appropriate model in which to examine the role of steroid glucur onidation. Northern blot analysis of simian RNA, hybridized with human UGT complementary DNA (cDNA) probes demonstrate the similarity of the transcrip ts. The simian UGT1A09 cDNA isolated from a liver library is 2396 bp and co ntains an open reading frame encoding 530 amino acids. The predicted primar y structure is most homologous to the human UGT1A9 (hUGT1A9) enzyme, which share 93% identity. Stable transfection of the monkey UGT1A09 (monUGT1A09) cDNA into HK293 cells, expresses a microsomal protein with an apparent mole cular mass of 55 kDa. Of the more than 30 endogenous substrates tested, bot h proteins show the highest activity on 4-hydroxyestradiol and 4-hydroxyest rone, followed by a-hydroxyestradiol and estradiol. RT-PCR analysis demonst rate that UGT1A9 transcript is expressed in several tissues, which include the prostate, testis, breast, ovary, and skin of the monkey and humans. The expression of UGT1A9 in extrahepatic estrogen-responsive tissues, and its high activity on estrogens is consistent with this enzyme having a role in estrogen metabolism.