Cold exposure induces a rapid increase in uncoupling protein (UCP) concentration in the brown adipose tissue (BAT) of euthyroid, but not hypothyroid, rats. To normalize this response with exogenous 3,5,3′-triiodothyronine (T3), it is necessary to cause systemic hyperthyroidism. In contrast, the same result can be obtained with just replacement doses of thyroxine (T4) and, in euthyroid rats, the normal response of UCP to cold occurs without hyperthyroid plasma T3 levels. Consequently, we explored the possibility that the cold-induced activation of the type II 5′-deiodinase resulted in high levels of nuclear T3 receptor occupancy in euthyroid rats. Studies were performed with pulse injections of tracer T3 or T4 in rats exposed to 4 degrees C for different lengths of time (1 h-3 wk). Within 4 h of cold exposure, we observed a significant increase in the nuclear [125I]T3 derived from the tracer [125I]T4 injections (T3[T4]) and a significant reduction in the nuclear [125I]T3 derived from [125I]T3 injections (T3[T3]). The number of BAT nuclear T3 receptors did not increase for up to 3 wk of observation at 4 degrees C. The mass of nuclear-bound T3 was calculated from the nuclear tracer [125I]T3[T3] and [125I]T3[T4] at equilibrium and the specific activity of serum T3 and T4, respectively. By 4 h after the initiation of the cold exposure, the receptors were greater than 95% occupied and remained so for the 3 weeks of observation. This effect of cold was hindered by prazosin, a drug that prevents the cold-induced activation of 5′-deiodinase. We conclude that the simultaneous activation of the deiodinase with adrenergic BAT stimulation serves the purpose of nearly saturating the nuclear T3 receptors.
Cold exposure rapidly induces virtual saturation of brown adipose tissue nuclear T3 receptors.
Bianco AC, Silva JE. Am J Physiol. October, 1988