title: Cytosolic T3-binding protein modulates dynamic alteration of T3-mediated gene expression in cells.
abstract: μ-Crystallin (CRYM) is also known as NADPH-dependent cytosolic T3-binding protein. A study using CRYM-null mice suggested that CRYM stores triiodothyronine (T3) in tissues. We previously established CRYM-expressing cells derived from parental GH3 cells. To examine the precise regulation of T3-responsive genes in the presence of CRYM, we evaluated serial alterations of T3-responsive gene expression by changing pericellular T3 concentrations in the media. We estimated the constitutive expression of three T3-responsive genes, growth hormone (GH), deiodinase 1 (Dio1), and deiodinase 2 (Dio2), in two cell lines. Subsequently, we measured the responsiveness of these three genes at 4, 8, 16, and 24 h after adding various concentrations of T3. We also estimated the levels of these mRNAs 24 and 48 h after removing T3. The levels of constitutive expression of GH and Dio1 were low and high in C8 cells, respectively, while Dio2 expression was not significantly different between GH3 and C8 cells. When treated with T3, Dio2 expression was significantly enhanced in C8 cells, while there were no differences in GH or Dio1 expression between GH3 and C8 cell lines. In contrast, removal of T3 retained the mRNA expression of GH and Dio2 in C8 cells. These results suggest that CRYM expression increases and sustains the T3 responsiveness of genes in cells, especially with alteration of the pericellular T3 concentration. The heterogeneity of T3-related gene expression is dependent on cellular CRYM expression in cases of dynamic changes in pericellular T3 concentration.
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Takeshige
authors.forename: Takashi
authors.initials: T
authors.lastname: Sekido
authors.forename: Jun-ichirou
authors.initials: J
authors.lastname: Kitahara
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Ohkubo
authors.forename: Dai
authors.initials: D
authors.lastname: Hiwatashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ishii
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Nishio
authors.forename: Teiji
authors.initials: T
authors.lastname: Takeda
authors.forename: Mitsuhisa
authors.initials: M
authors.lastname: Komatsu
authors.forename: Satoru
authors.initials: S
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003459:Crystallins / Q000378:metabolism / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D051379:Mice; D051381:Rats; D052683:Somatotrophs / Q000187:drug effects / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism* / Q000494:pharmacology*; D000090803:mu-Crystallins; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D003459:Crystallins; D013006:Growth Hormone; D007453:Iodide Peroxidase; D014284:Triiodothyronine; D000090803:mu-Crystallins; D000097564:Iodothyronine Deiodinase Type II; C000716470:Crym protein, mouse; C000716471:Crym protein, rat; C507436:selenodeiodinase type 1, mouse