Regulation of thyroid hormone sensitivity by differential expression of the thyroid hormone receptor during Xenopus metamorphosis.
During amphibian metamorphosis, a series of dynamic changes occur in a predetermined order. Hind limb morphogenesis begins in response to low levels of thyroid hormone (TH) in early prometamorphosis, but tail muscle cell death is delayed until climax, when TH levels are high. It takes about 20 days for tadpoles to grow from early prometamorphosis to climax. To study the molecular basis of the timing of tissue-specific transformations, we introduced thyroid hormone receptor (TR) expression constructs into tail muscle cells of Xenopus tadpoles. The TR-transfected tail muscle cells died upon exposure to a low level of thyroxine (T4). This cell death was suggested to be mediated by type 2 iodothyronine deiodinase (D2) that converts T4 to T3-the more active form of TH. D2 mRNA was induced in the TR-overexpressing cells by low levels of TH. D2 promoter contains a TH-response element (TRE) with a lower affinity for TR. These results show that the TR transfection confers the ability to respond to physiological concentrations of TH at early prometamorphosis to tail muscle cells through D2 activity and promotes TH signaling. We propose the positive feedback loop model to amplify the cell's ability to respond to low levels of T4.
Division of Embryology and Genetics, Institute for Amphibian Biology, Graduate School of Science, Hiroshima University, Higashihiroshima 739-8526, Japan.
Keisuke
K
Nakajima
Kenta
K
Fujimoto
Yoshio
Y
Yaoita
D000818:Animals; D016923:Cell Death; D024202:Electrophoretic Mobility Shift Assay; D025461:Feedback, Physiological; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006614:Hindlimb / Q000378:metabolism; D007453:Iodide Peroxidase / Q000378:metabolism; D007814:Larva / Q000235:genetics / Q000254:growth & development; D008675:Metamorphosis, Biological; D008845:Microinjections; D032342:Muscle Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D013623:Tail / Q000166:cytology / Q000378:metabolism; D013974:Thyroxine / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D059467:Transcriptome; D014162:Transfection; D014284:Triiodothyronine / Q000378:metabolism; D014982:Xenopus laevis / Q000235:genetics / Q000254:growth & development; D000097564:Iodothyronine Deiodinase Type II
D049452:Green Fluorescent Proteins; D007453:Iodide Peroxidase; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D013974:Thyroxine; D014284:Triiodothyronine; D000097564:Iodothyronine Deiodinase Type II