GENDER-RELATED DIFFERENCES IN THE AMOUNT AND FUNCTIONAL-STATE OF RAT-LIVER UDP-GLUCURONOSYLTRANSFERASE

The basis for gender-dependent differences in rates of glucuronidation of xenobiotics is uncertain. To clarify this issue, the glucuronidati on of p-nitrophenol was compared in liver microsomes from adult male a nd female rats. The activity of native UDP-glucuronosyltransferase was 47% higher in microsomes from male than from female rats. Immunoblott ing of microsomal protein with anti-UDP-glucuronosyltransferase antise rum revealed 66% more immunoreactive protein in male microsomes. A kin etic method for measuring glucuronidating enzyme content confirmed the result of the immunoblot. Responses of UDP-glucuronosyltransferase to activation by palmitoyl-lysophosphatidylcholine or high pressure indi cated that the activity of the enzyme was more latent in male than in female microsomes. Differences in enzyme latency could be due to diffe rences in membrane structure. A comparison of microsomal fatty acid co mposition revealed significantly higher levels of oleic and linoleic a cids and lower levels of stearic and docosahexaenoic acids in male tha n in female microsomes. The phospholipid composition, ratio of cholest erol: phospholipid, and membrane fluidity were similar in male and fem ale microsomes. These results indicate that gender-dependent differenc es in UDP-glucuronosyltransferase activity are due to differences in b oth the amount and functional state of the enzyme.