caa a22 4500 47712609X CHVBK 20180405111650.0 cr unu---uuuuu 170330e19970901xx s 000 0 eng 10.1023/A:1012130118186 doi (NATIONALLICENCE)springer-10.1023/A:1012130118186 Sex Hormones Differentially Regulate Isoforms of UDP-Glucuronosyltransferase [Elektronische Daten] [Simone Strasser, Sheree Smid, Maurice Mashford, Paul Desmond] Purpose. To investigate the role of sex hormones in the regulation of UDP-glucuronosyltransferase (UGT). Methods. We examined liver from adult, prepubertal, gonadectomised and gonadectomised plus hormone replaced rats of both sexes. Immuno-histochemistry and immunoblots were performed using a polyclonal UGT antibody to a number of family 1 and family 2 UGT isoforms. Northern blot analysis was performed utilising cDNA probes to family 1 and family 2 isoforms. Results. Immunohistochemistry demonstrated variations in intensity and distribution of staining in the hormonally manipulated rats. Immunoblots showed variations in individual band intensity between rat groups. Immunoblots using a more specific antibody (anti-17β-hydroxysteroid UGT, which recognises UGT2B3 and UGT2B2) demonstrated marked differences between male and female rats and significant alterations after gonadectomy and testosterone replacement in the male rats. In northern analysis, UGT2B3 and 2B1 mRNA were significantly higher in adult males than females, and in prepubertal males compared to prepubertal females. In male rats, gonadectomy resulted in a 45−53% reduction in UGT2B3 and 2B1 levels respectively, which increased significantly with testosterone treatment to greater than normal adult levels. No change in UGT2B3 or 2B1 occurred after gonadectomy in females. In contrast, UGT1*1 mRNA tended to be higher in adult female and prepubertal female rats than in their male counterparts. In females, gonadectomy resulted in significant up-regulation of UGT1*1, while gonadectomy plus oestradiol treatment resulted in markedly reduced levels. UGT1*1 mRNA was not significantly altered by gonadectomy in males. Conclusions. This study demonstrates the differential effects of sex hormones on the expression of isoforms from the two phylogenetically distinct UGT families. Plenum Publishing Corporation, 1997 drug metabolising enzyme nationallicence oestradiol nationallicence testosterone nationallicence UDP-glucuronosyltransferase nationallicence Strasser Simone Department of Gastroenterology, St. Vincent's Hospital, Fitzroy, Victoria, Australia aut Smid Sheree Department of Gastroenterology, St. Vincent's Hospital, Fitzroy, Victoria, Australia aut Mashford Maurice Department of Clinical Pharmacology, St. Vincent's Hospital, Fitzroy, Victoria, Australia aut Desmond Paul Department of Clinical Pharmacology, St. Vincent's Hospital, Fitzroy, Victoria, Australia aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/9(1997-09-01), 1115-1121 0724-8741 14:9<1115 1997 14 11095 https://doi.org/10.1023/A:1012130118186 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012130118186 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Strasser Simone Department of Gastroenterology, St. Vincent's Hospital, Fitzroy, Victoria, Australia aut NATIONALLICENCE 700 1- Smid Sheree Department of Gastroenterology, St. Vincent's Hospital, Fitzroy, Victoria, Australia aut NATIONALLICENCE 700 1- Mashford Maurice Department of Clinical Pharmacology, St. Vincent's Hospital, Fitzroy, Victoria, Australia aut NATIONALLICENCE 700 1- Desmond Paul Department of Clinical Pharmacology, St. Vincent's Hospital, Fitzroy, Victoria, Australia aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/9(1997-09-01), 1115-1121 0724-8741 14:9<1115 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer