Hepatic UDP-glucuronyltransferase(s) activity toward thyroid hormones in rats: Induction and effects on serum thyroid hormone levels following treatment with various enzyme inducers

Abstract

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 (T 4; hUDP-GT-T 4) was induced by treatment with β-naphthoflavone, 3-methylcholanthrene (3-MC), polychlorinated biphenyls, or pregnenolone-16α-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-T 4 for these inducers was approximately the same as that of hUDP-GT activity toward triiodothyronine (T 3; hUDP-GT-T 3), indicating that these two thyroid hormones (T 4 and T 3) are glucuronidated by the same hUDP-GT(s). Moreover, the induction profile of both hUDP-GT-T 4 and hUDP-GT-T 3 was similar to that of hUDP-GT toward 1-naphthol, but not chloramphenicol, suggesting that T 4 and T 3 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 T 4 levels clearly correlated with an increase in hUDP-GT-T 4 activity, inducating that serum T 4 levels are directly affected by hUDP-GT-T 4 activity. However, no direct correlation between decrease in thyroid hormone levels and compensatory increase in TSH levels was found.