Distribution of uridine diphosphate-glucuronosyltransferase (UGT) expression and activity in cynomolgus monkey tissues: Evidence for differential expression of steroid-conjugating UGT enzymes in steroid target tissues

Based on the similarity of pathways and enzymes involved in steroid metabol ism, simians represent a relevant animal model to study steroid elimination by glucuronidation. In this study the tissue distribution of UDP-glucurono syltransferase (UGT) transcripts, proteins, and enzymatic activities were e xamined in 24 different cynomolgus monkey tissues. RT-PCR and Western blot analysis on total RNA and microsomal proteins demonstrated the presence of UGT1A and UGT2B transcripts and proteins in a wide range of tissues includi ng steroid target tissues. Glucuronidation activity on eugenol, 5 alpha-and rostane-3 alpha,17 beta-diol, androsterone, and 4-hydroxyestradiol was meas ured using tissue homogenates and radiolabeled [C-14]UDP- glucuronic acid. All tissues contained conjugation activity on these substrates, but glucuro nidation rates were significantly lower in steroid target tissues than in l iver, kidney, or gut. Rowever, the ratio of steroid glucuronidation vs, eug enol glucuronidation was higher in steroid target tissues, suggesting a dif ferential expressionofsteroidconjugating enzymes in these tissues. Taken to gether, these results clearly demonstrate the presence of steroid glucuroni dation enzymes in extrahepatic steroid target tissues and support the hypot hesis that steroid glucuronidation is an important intracrine pathway invol ved in termination of steroid signaling.