EFFECTS OF THYROID-HORMONE ON NOREPINEPHRINE SIGNALING IN BROWN ADIPOSE-TISSUE .1. BETA(1)-ADRENERGIC AND BETA(2)-ADRENERGIC RECEPTORS AND CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE GENERATION

Brown adipose tissue (BAT) thermogenesis is activated by the sympathet ic nervous system. BAT responses to norepinephrine are blunted in hypo thyroidism and are rapidly restored by thyroid hormone. We examined in rats the effects of thyroid hormone on BAT beta(1)- and <beta(2)-adre nergic receptors (AR) expression and capacity to generate cAMP in resp onse to adrenergic stimulation. Both are reduced in hypothyroidism. Th e reduction in cAMP generation is equal to or greater than that in bet a(1,2)-AR; it is the same whether cAMP production is stimulated with n orepinephrine, selective beta(3)-AR agonists, or forskolin; and it is not affected by the inhibition of phosphodiesterase. Both beta(1,2)-AR and the capacity to generate cAMP were slowly corrected by thyroid ho rmone. T-3 normalized beta(1,2)-AR between 1 and 2 days, whereas the i mprovement in cAMP generation lagged 1 or 2 days behind. Within 2 days of acclimation of athyreotic rats at 30 C, the number of beta(1,2)-AR reached the euthyroid level, whereas exposure to 4 C decreased these receptors. We reached the following conclusions: 1) BAT beta(1,2)-AR a nd capacity to generate cAMP are reduced in hypothyroidism; 2) the lat ter, however, is not explained by the reduction in beta(1,2)-AR, but, rather, reflects a fault at the postreceptor level; 3) the reduction i n beta(1,2)-AR number is largely caused by the cold stress derived fro m the low metabolic rate of the hypothyroid state; and 4) the slow res toration of both receptor number and capacity to generate cAMP after T -3 are not consistent with these defects being a significant factor in the previously reported blunted uncoupling protein responses to adren ergic stimulation in hypothyroidism.