title: Intrinsic regulation of thyroid function by thyroglobulin.
abstract: BACKGROUND
  The established paradigm for thyroglobulin (Tg) function is that of a high molecular weight precursor of the much smaller thyroid hormones, triiodothyronine (T3) and thyroxine (T4). However, speculation regarding the cause of the functional and morphologic heterogeneity of the follicles that make up the thyroid gland has given rise to the proposition that Tg is not only a precursor of thyroid hormones, but that it also functions as an important signal molecule in regulating thyroid hormone biosynthesis.
  
  
  CONCLUSIONS
  Evidence supporting this alternative paradigm of Tg function, including the up- or downregulation by colloidal Tg of the transcription of Tg, iodide transporters, and enzymes employed in Tg iodination, and also the effects of Tg on the proliferation of thyroid and nonthyroid cells, is examined in the present review. Also discussed in detail are potential mechanisms of Tg signaling in follicular cells.
  
  
  CONCLUSIONS
  Finally, we propose a mechanism, based on experimental observations of Tg effects on thyroid cell behavior, that could account for the phenomenon of follicular heterogeneity as a highly regulated cycle of increasing and decreasing colloidal Tg concentration that functions to optimize thyroid hormone production through the transcriptional activation or suppression of specific genes.
authors.affiliation: 1 Department of Medicine, Uniformed Services University of the Health Sciences , Bethesda, Maryland.
authors.forename: Donald F
authors.initials: DF
authors.lastname: Sellitti
authors.forename: Koichi
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000502:physiology; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D015870:Gene Expression; D006706:Homeostasis; D006801:Humans; D008954:Models, Biological; D011956:Receptors, Cell Surface / Q000502:physiology; D015398:Signal Transduction; D013954:Thyroglobulin / Q000235:genetics / Q000502:physiology*; D013961:Thyroid Gland / Q000033:anatomy & histology / Q000166:cytology / Q000502:physiology*; D013963:Thyroid Hormones / Q000096:biosynthesis; D014157:Transcription Factors / Q000235:genetics
chemical_list: D037263:Asialoglycoprotein Receptor; D011956:Receptors, Cell Surface; D013963:Thyroid Hormones; D014157:Transcription Factors; C032198:thyroglobulin receptor; D013954:Thyroglobulin