INTRODUCTION: 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.
CONCLUSION: 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.