Hepatic UDP-glucuronyltransferase(s) activity toward thyroid hormones in rats: induction and effects on serum thyroid hormone levels following treatment with various enzyme inducers.
Induction of hepatic UDP-glucuronyltransferase(s) (hUDP-GT(s] activity toward thyroid hormones and the relationship between the activity and the serum thyroid hormones or the thyroid stimulating hormone (TSH) level were examined in male Sprague-Dawley rats after four consecutive ip doses of various hepatic enzyme inducers at 75-150 mg/kg/day. hUDP-GT activity toward thyroxine (T4; hUDP-GT-T4) was induced by treatment with beta-naphthoflavone, 3-methylcholanthrene (3-MC), polychlorinated biphenyls, or pregnenolone-16 alpha-carbonitrile. However, no significant induction was observed for isosafrole administration and in the cases of phenobarbital and 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane slight decreases were found. The induction profile of hUDP-GT-T4 for these inducers was approximately the same as that of hUDP-GT activity toward triiodothyronine (T3; hUDP-GT-T3), indicating that these two thyroid hormones (T4 and T3) are glucuronidated by the same hUDP-GT(s). Moreover, the induction profile of both hUDP-GT-T4 and hUDP-GT-T3 was similar to that of hUDP-GT toward 1-naphthol, but not chloramphenicol, suggesting that T4 and T3 belong to the so-called group-1 substrates which are preferentially glucuronidated by hUDP-GT(s) inducible by treatment with 3-MC. Decreases in serum T4 levels clearly correlated with an increase in hUDP-GT-T4 activity, indicating that serum T4 levels are directly affected by hUDP-GT-T4 activity. However, no direct correlation between decrease in thyroid hormone levels and compensatory increase in TSH levels was found.
Saito
K
K
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., Osaka, Japan.
Kaneko
H
H
Sato
K
K
Yoshitake
A
A
Yamada
H
H
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004790:Enzyme Induction; D014453:Glucuronosyltransferase / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000033:anatomy & histology / Q000201:enzymology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013961:Thyroid Gland / Q000033:anatomy & histology; D013963:Thyroid Hormones / Q000097:blood*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D013963:Thyroid Hormones; D014284:Triiodothyronine; D013972:Thyrotropin; D014453:Glucuronosyltransferase; D013974:Thyroxine