BACKGROUND: Thyroid hormones are involved in developmental and homeostatic 
processes in several tissues. Their action results in different outcomes 
depending on the developmental stage, tissue and/or cellular context. 
Interestingly, their pleiotropic roles are conserved across vertebrates. It is 
largely documented that thyroid hormones act via nuclear receptors, the TRs, 
which are transcription factors and whose activity can be modulated by the local 
availability of the hormone T3. In the "classical view", the T3-induced 
physiological response depends on the expression of specific TR isoforms and the 
iodothyronine deiodinase selenoenzymes that control the local level of T3, thus 
TR activity.
SCOPE OF THE REVIEW: Recent data have clearly established that the functionality 
of TRs is coordinated and integrated with other signaling pathways, specifically 
at the level of stem/progenitor cell populations. Here, we summarize these data 
and propose a new and intriguing role for thyroid hormones in two selected 
examples.
MAJOR CONCLUSIONS: In the intestinal epithelium and the retina, TRα1 and TRβ2 
are expressed at the level of the precursors where they induce cell 
proliferation and differentiation, respectively. Moreover, these different 
functions result from the integration of the hormone signal with other intrinsic 
pathways, which play a fundamental role in progenitor/stem cell physiology.
GENERAL SIGNIFICANCE: Taken together, the interaction of TRs with other 
signaling pathways, specifically in stem/progenitor cells, is a new concept that 
may have biological relevance in therapeutic approaches aimed to target stem 
cells such as tissue engineering and cancer. This article is part of a Special 
Issue entitled Thyroid hormone signalling.