SEX-HORMONES DIFFERENTIALLY REGULATE ISOFORMS OF UDP-GLUCURONOSYLTRANSFERASE

Purpose, To investigate the role of sex hormones in the regulation of UDP-glucuronosyltransferase (UGT). Methods, We examined liver from adu lt, prepubertal, gonadectomised and gonadectomised plus hormone replac ed rats of both sexes. Immunohistochemistry and immunoblots were perfo rmed using a polyclonal UGT antibody to a number of family 1 and famil y 2 UGT isoforms. Northern blot analysis was performed utilising cDNA probes to family 1 and family 2 isoforms. Results, Immunohistochemistr y demonstrated variations in intensity and distribution of staining in the hormonally manipulated rats. Immunoblots showed variations in ind ividual band intensity between rat groups. Immunoblots using a more sp ecific antibody (anti-17 beta-hydroxysteroid UGT, which recognises UGT 2B3 and UGT2B2) demonstrated marked differences between male and femal e rats and significant alterations after gonadectomy and testosterone replacement in the male rats. In northern analysis, UGT2B3 and 2B1 mRN A were significantly higher in adult males than females, and in prepub ertal males compared to prepubertal females. In male rats, gonadectomy resulted in a 45-53% reduction in UGT2B3 and 2B 1 levels respectively , which increased significantly with testosterone treatment to greater than normal adult levels. No change in UGT2B3 or 2B 1 occurred after gonadectomy in females. In contrast, UGT11 mRNA tended to be higher i n adult female and prepubertal female rats than in their male counterp arts. In females, gonadectomy resulted in significant up-regulation of UGT11, while gonadectomy plus oestradiol treatment resulted in marke dly reduced levels. UGT11 mRNA was not significantly altered by gonad ectomy in males. Conclusions. This study demonstrates the differential effects of sex hormones on the expression of isoforms from the two ph ylogenetically distinct UGT families.