title: Thyroglobulin suppresses thyroid-specific gene expression in cultures of normal but not neoplastic human thyroid follicular cells.
abstract: BACKGROUND
  It was shown in the rat thyroid that thyroglobulin (Tg) stored in the follicular lumen is a potent regulator of thyroid-specific gene expression to maintain the function of individual follicles. However, the actions of Tg as a regulatory molecule in human thyroid have not been studied.
  
  
  OBJECTIVE
  Our objective was to determine the effect of Tg on gene expression in normal and diseased human thyroid and to examine whether the proposed model of negative-feedback autocrine regulation of thyroid function by Tg is applicable in the human as well as the rat.
  
  
  METHODS
  Primary cultures of human thyrocytes were established from normal thyroid, Graves' disease thyroid, adenomatous goiter, follicular adenoma, and papillary carcinoma tissues obtained during surgery. Cells were stimulated with physiologic (ie, follicular) concentrations of Tg, and mRNA and protein expression of genes involved in thyroid hormonogenesis were evaluated. The effects of Tg on thyroid-specific gene expression were also assessed in 2 human papillary carcinoma cell lines.
  
  
  RESULTS
  Transcript levels of genes participating in thyroid hormone biosynthesis were significantly reduced by Tg in thyrocyte cultures derived from normal and Graves' thyroid, but not in cultures derived from thyroid neoplasms and adenomatous goiter.
  
  
  CONCLUSIONS
  It was confirmed that Tg acts as a negative-feedback regulator of gene expression in human thyrocytes, suggesting that Tg signaling may constitute a common mechanism for maintaining thyroid homeostasis in species with follicular thyroid morphology. However, certain diseases of intrinsic thyroid overgrowth appear to be associated with an escape from the regulatory mechanism of Tg.
authors.affiliation: Laboratory of Molecular Diagnostics (Y.I., Y.L., K.S.), Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo 189-0002, Japan; Thyroid Disease Institute (K.Y., M.K., Y.S., E.Y, T.Y.), Kanaji Thyroid Hospital, Tokyo 114-0015, Japan; and Department of Medicine (D.F.S.), Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ishido
authors.forename: Kazuko
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Kammori
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Sugishita
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Luo
authors.forename: Emiko
authors.initials: E
authors.lastname: Yamada
authors.forename: Tetsu
authors.initials: T
authors.lastname: Yamada
authors.forename: Donald F
authors.initials: DF
authors.lastname: Sellitti
authors.forename: Koichi
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000473:pathology; D000328:Adult; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000235:genetics / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006042:Goiter / Q000235:genetics / Q000473:pathology; D006111:Graves Disease / Q000235:genetics / Q000473:pathology; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D033862:Iron-Binding Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009928:Organ Specificity / Q000235:genetics; D061251:Primary Cell Culture; D013954:Thyroglobulin / Q000494:pharmacology*; D013961:Thyroid Gland / Q000166:cytology* / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D001324:Autoantigens; D033862:Iron-Binding Proteins; D013954:Thyroglobulin; C056658:TPO protein, human; D007453:Iodide Peroxidase