Thyroid hormones (TH) are essential for brain development. However, information 
on if and how this key endocrine factor affects adult neurogenesis is 
fragmentary. We thus investigated the effects of TH on proliferation and 
apoptosis of stem cells in the subventricular zone (SVZ), as well as on 
migration of transgene-tagged neuroblasts out of the stem cell niche. 
Hypothyroidism significantly reduced all three of these processes, inhibiting 
generation of new cells. To determine the mechanisms relaying TH action in the 
SVZ, we analyzed which receptor was implicated and whether the effects were 
played out directly at the level of the stem cell population. The alpha TH 
receptor (TRalpha), but not TRbeta, was found to be expressed in nestin positive 
progenitor cells of the SVZ. Further, use of TRalpha mutant mice showed TRalpha 
to be required to maintain full proliferative activity. Finally, a direct TH 
transcriptional effect, not mediated through other cell populations, was 
revealed by targeted gene transfer to stem cells in vivo. Indeed, TH directly 
modulated transcription from the c-myc promoter reporter construct containing a 
functional TH response element containing TRE but not from a mutated TRE 
sequence. We conclude that liganded-TRalpha is critical for neurogenesis in the 
adult mammalian brain.