Influence of iodine-deficiency on thyroid hormones homeostasis in rats.
Little is known about the kinetics and metabolism of thyroid hormones in the hypothyroid state. In order to optimize hormone replacement therapy, it is important to understand variations in the kinetics and metabolism of thyroid hormones. To investigate these factors, we monitored serum thyroxine (T₄) and triiodothyronine (T₃) levels in iodine-deficient diet (ID) rats using online solid-phase extraction liquid chromatography-mass spectrometry/mass spectrometry (Online SPE LC-MS/MS). Furthermore, we evaluated supply and turnover rates of T₄ in ID rats using a stable isotope-labeled T₄ ([¹³C₉]T₄). Although serum T₄ levels gradually declined after beginning ID treatment, T₃ levels were unchanged throughout the experimental period. After intravenous administration of [¹³C₉]T₄ to ID rats, [¹³C₉]T₄ levels were monitored. We previously reported that significant differences of supply and turnover rates for T₄ were observed in surgically thyroidectomized (Tx) rats. Surprisingly, there were no differences of supply and turnover rates for T₄ between ID rats and intact rats. In conclusion, there were significant differences of supply and turnover rates for T₄ between the hypothyroid states of ID and Tx rats. In ID rats, T₃ might be preferentially biosynthesized in the thyroid, and ID treatment might not affect T₄ kinetics. Our method, online SPE LC-MS/MS monitoring using a stable isotope tracer, has the potential to be used as a diagnostic tool to investigate the pathogenesis of thyroid disease and is valuable for optimizing the dosage in thyroid hormone replacement therapy.
Pharmacokinetics Research Department, ASKA Pharmaceutical Co., Ltd., Kawasaki 213-8522, Japan. minato-k@aska-pharma.co.jp
Kouichi
K
Minato
Hidenori
H
Nagao
Tetsuya
T
Imazu
Kenjo
K
Takahashi
D000818:Animals; D006706:Homeostasis; D007455:Iodine / Q000172:deficiency*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013961:Thyroid Gland / Q000378:metabolism; D013965:Thyroidectomy; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood*; D014284:Triiodothyronine / Q000097:blood*
D014284:Triiodothyronine; D013972:Thyrotropin; D007455:Iodine; D013974:Thyroxine