title: Effects of triiodothyronine on turnover rate and metabolizing enzymes for thyroxine in thyroidectomized rats.
abstract: OBJECTIVE
  Previous studies in rats have indicated that surgical thyroidectomy represses turnover of serum thyroxine (T4). However, the mechanism of this process has not been identified. To clarify the mechanism, we studied adaptive variation of metabolic enzymes involved in T4 turnover.
  
  
  METHODS
  We compared serum T4 turnover rates in thyroidectomized (Tx) rats with or without infusion of active thyroid hormone, triiodothyronine (T3). Furthermore, the levels of mRNA expression and activity of the metabolizing enzymes, deiodinase type 1 (D1), type 2 (D2), uridine diphosphate-glucuronosyltransferase (UGT), and sulfotransferase were also compared in several tissues with or without T3 infusion.
  
  
  RESULTS
  After the T3 infusion, the turnover rate of serum T4 in Tx rats returned to normal. Although mRNA expression and activity of D1 decreased significantly in both liver and kidneys without T3 infusion, D2 expression and activity increased markedly in the brain, brown adipose tissue, and skeletal muscle. Surprisingly, hepatic UGT mRNA expression and activity in Tx rats increased significantly in comparison with normal rats, and returned to normal after T3 infusion.
  
  
  CONCLUSIONS
  This study suggests that repression of the disappearance of serum T4 in rats after Tx is a homeostatic response to decreased serum T3 concentrations. Additionally, T4 glucuronide is a storage form of T4, but may also have biological significance. These results suggest strongly that repression of deiodination of T4 by D1 in the liver and kidneys plays a major role in thyroid hormone homeostasis in Tx rats, and that hepatic UGT also plays a key role in this mechanism.
authors.affiliation: Pharmacokinetics Research Department of ASKA Pharmaceutical Co., Ltd., Kawasaki, Japan. Electronic address: nagao-h@aska-pharma.co.jp.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Nagao
authors.affiliation: Pharmacokinetics Research Department of ASKA Pharmaceutical Co., Ltd., Kawasaki, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Pharmacokinetics Research Department of ASKA Pharmaceutical Co., Ltd., Kawasaki, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Imazu
authors.affiliation: Department of Analytical Research, ASKA Pharma Medical Co., Ltd., Kawasaki, Japan.
authors.forename: Kenjo
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Pharmacokinetics Research Department of ASKA Pharmaceutical Co., Ltd., Kawasaki, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Aoki
authors.affiliation: Pharmacokinetics Research Department of ASKA Pharmaceutical Co., Ltd., Kawasaki, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Minato
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D005965:Glucuronates / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013965:Thyroidectomy; D013974:Thyroxine / Q000031:analogs & derivatives / Q000097:blood* / Q000378:metabolism; D014284:Triiodothyronine / Q000008:administration & dosage / Q000097:blood*
chemical_list: D005965:Glucuronates; D012333:RNA, Messenger; D014284:Triiodothyronine; C054785:thyroxine glucuronide; D014453:Glucuronosyltransferase; D013974:Thyroxine
keywords: Deiodinases; Isotope tracer; On-line SPE LC-MS/MS; Sulfotransferases; Thyroid hormones; Thyroidectomy; Turnover rate; UDP-glucuronosyltransferases