title: Molecular and cell biological effects of 3,5,3'-triiodothyronine on progenitor cells of the enteric nervous system in vitro.
abstract: BACKGROUND
  Thyroid hormones play important roles in the development of neural cells in the central nervous system. Even minor changes to normal thyroid hormone levels affect dendritic and axonal outgrowth, sprouting and myelination and might even lead to irreversible damages such as cretinism. Despite our knowledge of the influence on the mammalian CNS, the role of thyroid hormones in the development of the enteric nervous system (ENS) still needs to be elucidated. In this study we have analyzed for the first time the influence of 3,5,3'-triiodothyronine (T3) on ENS progenitor cells using cell biological assays and a microarray technique.
  
  
  RESULTS
  In our in vitro model, T3 inhibited cell proliferation and stimulated neurite outgrowth of differentiating ENS progenitor cells. Microarray analysis revealed a group of 338 genes that were regulated by T3 in differentiating enterospheres. 67 of these genes are involved in function and development of the nervous system. 14 of them belong to genes that are involved in axonal guidance or neurite outgrowth. Interestingly, T3 regulated the expression of netrin G1 and endothelin 3, two guidance molecules that are involved in human enteric dysganglionoses.
  
  
  CONCLUSIONS
  The results of our study give first insights how T3 may affect the enteric nervous system. T3 is involved in proliferation and differentiation processes in enterospheres. Microarray analysis revealed several interesting gene candidates that might be involved in the observed effects on enterosphere differentiation. Future studies need to be conducted to better understand the gene to gene interactions.
authors.affiliation: Institute of Anatomy, University of Tuebingen, Oesterbergstrasse 3, 72074 Tuebingen, Germany. Electronic address: rmohr@anatom.uni-tuebingen.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Mohr
authors.forename: Peter
authors.initials: P
authors.lastname: Neckel
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Susanne
authors.initials: S
authors.lastname: Stachon
authors.forename: Katharina
authors.initials: K
authors.lastname: Nothelfer
authors.forename: Karin
authors.initials: K
authors.lastname: Schaeferhoff
authors.forename: Florian
authors.initials: F
authors.lastname: Obermayr
authors.forename: Michael
authors.initials: M
authors.lastname: Bonin
authors.forename: Lothar
authors.initials: L
authors.lastname: Just
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D019334:Endothelin-3 / Q000235:genetics / Q000378:metabolism; D017615:Enteric Nervous System / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D000075385:Netrins; D020411:Oligonucleotide Array Sequence Analysis; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics / Q000378:metabolism; D037042:Thyroid Hormone Receptors beta / Q000235:genetics / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D019334:Endothelin-3; D009419:Nerve Tissue Proteins; D000075385:Netrins; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta; C413653:netrin-G1; D014284:Triiodothyronine