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Regulation of thyroid hormone sensitivity by differential expression of the thyroid hormone receptor during X enopus metamorphosis
Author(s) -
Nakajima Keisuke,
Fujimoto Kenta,
Yaoita Yoshio
Publication year - 2012
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2012.01614.x
Subject(s) - biology , xenopus , thyroid hormone receptor , thyroid , iodothyronine deiodinase , medicine , deiodinase , endocrinology , hormone , metamorphosis , receptor , thyroid hormone receptor beta , morphogenesis , transfection , thyroid hormone receptor alpha , microbiology and biotechnology , triiodothyronine , hormone receptor , nuclear receptor , cell culture , gene , transcription factor , genetics , cancer , botany , breast cancer , larva
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 X enopus tadpoles. The TR ‐transfected tail muscle cells died upon exposure to a low level of thyroxine ( T 4). This cell death was suggested to be mediated by type 2 iodothyronine deiodinase ( D 2) that converts T 4 to T 3—the more active form of TH . D 2 m RNA was induced in the TR ‐overexpressing cells by low levels of TH . D 2 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 D 2 activity and promotes TH signaling. We propose the positive feedback loop model to amplify the cell's ability to respond to low levels of T 4.