GENDER-SPECIFIC CHANGES IN THYROID HORMONE-GLUCURONIDATING ENZYMES INRAT-LIVER DURING SHORT-TERM FASTING AND LONG-TERM FOOD RESTRICTION

Glucuronidation is a major pathway of thyroid hormone metabolism in ra ts, involving at least three different hepatic UDP-glucuronyltransfera ses (UGTs): bilirubin UGT, phenol UGT and androsterone UGT. We have st udied the effects of short-term (3 days) fasting and long-term (3 week s) food restriction to one-third of normal intake (FR33) on hepatic UG T activities for thyroxine (T-4), triiodothyronine (T-3), bilirubin an d androsterone in male and female Wistar rats with either a functional (high activity, HA) or a defective (low activity, LA) androsterone UG T gene. Because food deprivation is known to induce centrally mediated hypothyroidism in rats, results were compared with those obtained in methimazole (MMI)-induced hypothyroid rats. Both fasting and FR33 prod uced largely parallel increases in T-4 and bilirubin UGT activities. T hese effects were greater in males than in females, and were reproduce d in MMI-treated rats. In male and female HA rats, fasting induced ins ignificant increases in T-3 UGT activity and had no effect on androste rone UGT activity. In male HA rats, FR33 was associated with an increa se in T-3 UGT activity, while androsterone UGT activity showed little change. However, in female HA rats both T-3 and androsterone UGT activ ities were markedly decreased by FR33. Triiodothyronine UGT activity i n LA rats was strongly decreased compared with HA rats, but was not fu rther decreased by FR33 in female LA rats, supporting the importance o f androsterone UGT for T-3 glucuronidation. These results demonstrate different sex-dependent effects of food deprivation on hepatic T-4 and T-3 glucuronidation that are associated with changes in the expressio n of bilirubin UGT and androsterone UGT, respectively. For the increas ed T-4 and bilirubin UGT activities at least, these effects appear to be mediated by the hypothyroid state of the (semi)starved animals.