Phenobarbital, beta-naphthoflavone, clofibrate, and pregnenolone-16alpha-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-16alpha-carbonitrile (PCN), and beta-naphthoflavone (NF) on hepatic microsomal thyroxin (T4)- UDP-glucuronosyl transferase (UGT) and triiodothyronine (T3)- UGT activities and thyroid function were evaluated in OF-1 male mice after a 14-day po administration. CLO, PB, and PCN induced histological liver hypertrophy, increases in liver weights, in microsomal protein and cytochrome P450 contents as well as increases in specific UGT activities. Despite this, no significant changes in T4-UGT and T3-UGT activities occurred after treatment by any of these compounds. Furthermore, no significant changes in serum T4 and T3 levels were observed and thyroid histology was not affected. NF treatment induced microvacuolation of hepatocytes but did not affect any of the other tested parameters. The results show that, in contrast to the widely described effects in rats, liver enzyme inducers do not affect hepatic thyroid hormone metabolism and thyroid function in mice, suggesting that this species should be less sensitive to thyroid tumor promotion by hepatic microsomal enzyme inducers than rats.
Faculté de Médecine et de Pharmacie, Laboratoire de Biologie Cellulaire, 4 place Saint-Jacques, Besançon, 25030, France.
C
C
Viollon-Abadie
D
D
Lassere
E
E
Debruyne
L
L
Nicod
N
N
Carmichael
L
L
Richert
D000818:Animals; D002994:Clofibrate / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D010634:Phenobarbital / Q000494:pharmacology*; D011285:Pregnenolone Carbonitrile / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013961:Thyroid Gland / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D013963:Thyroid Hormones / Q000378:metabolism*; D019324:beta-Naphthoflavone / Q000494:pharmacology*
D013963:Thyroid Hormones; D011285:Pregnenolone Carbonitrile; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; D002994:Clofibrate; D010634:Phenobarbital