Phenobarbital, beta-naphthoflavone, clofibrate, and pregnenolone-16 alpha-carbonitrile do not affect hepatic thyroid hormone UDP-glucuronosyl transferase activity, and thyroid gland function in mice

The effects of representative liver enzyme inducers such as clofibrate (CLO ), phenobarbital (PB), pregnenolone-16 alpha-carbonitrile (PCN), and beta-n aphthoflavone (NF) on hepatic microsomal thyroxin (T-4)- UDP-glucuronosyl t ranferase (UGT) and triiodothyronine (T-3)- UGT activities and thyroid func tion were evaluated in OF-1 male mice after a 14-day po administration. CLO , PB, and PCN induced histological liver hypertrophy, increases in liver we ights, in microsomal protein and cytochrome P450 contents as well as increa ses in specific UGT activities. Despite this, no significant changes in T-4 -UGT and T-3-UGT activities occurred after treatment by any of these compou nds. Furthermore, no significant changes in serum T-4 and T-3 levels were o bserved and thyroid histology was not affected. NF treatment induced microv acuolation of hepatocytes but did not affect any of the other tested parame ters. The results show that, in contrast to the widely described effects in rats, liver enzyme inducers do not affect hepatic thyroid hormone metaboli sm and thyroid function in mice, suggesting that this species should be les s sensitive to thyroid tumor promotion by hepatic microsomal enzyme inducer s than rats. (C) 1999 Academic Press.