See related article, pages 97–105. seems to be more important in mediating the chronotropic and inotropic effects of TH on the heart (15, 16). The lower body temperature of α1TR-knockout (α1TR-KO), but not βTR-KO, mice (15, 16) appears to implicate the α1TR in the thermogenic effect of TH. Following up on this observation, Ribeiro et al.(9) now show that αTR is essential for TH to restore the levels of a factor in the NE signaling pathway, downstream of the adrenergic receptors, that is limiting in hypothyroidism. They observe that when hypothyroid rats are treated with the βTR-selective analogue GC1 (9), not only does cAMP generation in BAT remain impaired, but the animals’ heart rate fails to increase, in contrast to animals treated with T3. Thus, the α1TR isoform appears to be important for NE signaling in other tissues as well. In turn, this finding suggests that the impaired NE signaling is at the core of the thermoregulatory deficit in the α1TR-deficient mice, a conclusion that is further supported by the fact that FT remains impaired in hypothyroid mice treated with GC1, even though the analogue restores normal levels of UCP. One might argue that the lower body temperature of the α1TR-KO mice at room temperature is also due to the sympathetic deficiency. Since 22–23 C (“room temperature”) is below thermoneutrality for small rodents (28–30 C), mice maintained at 22 C will need to activate FT to maintain their core temperatures. This reasoning, however, does not exclude the participation of α1TR in the maintenance of OT, as discussed below.