Effects of hypothyroidism and hyperthyroidism on thermogenic responses to selective and nonselective beta-adrenergic agonists in rats.

Oxygen consumption (VO2) and mitochondrial guanosine diphosphate (GDP) binding of interscapular brown adipose tissue (BAT) were measured in hypothyroid, hyperthyroid and euthyroid rats after stimulations with selective and nonselective beta-adrenoceptor agonists: BRL 35135A (BRL) and Isoprenaline (ISO). Resting VO2, VO2 increment and mitochondrial GDP binding after beta-adrenergic stimulations were lower in hypothyroid rats than in the euthyroid group. The reduced responses were more marked for ISO than for BRL. Restion VO2 and VO2 increment after beta-adrenergic stimulations were higher in hyperthyroid rats than in the eurthyroid group; the increment was more marked for BRL than for ISO. In hyperthyroidism, mitochondrial GDP binding after BRL and after ISO was in the same magnitude; it was higher in the hyperthyroid than in the euthyroid group after BRL but not after ISO. The different thermogenic responses after ISO and BRL stimulations suggest that BRL is acting on a beta-adrenoceptor differing from the beta-1 and beta-2 adrenoceptors responsible for the effects of ISO. Activation of thermogenesis via the beta-3 adrenoceptor seems to be less dependent on the permissive levels of thyroid hormones than activation via beta-1 and/or beta-2 adrenoceptors. The beta-3 adrenoceptor may be more sensitive to increased levels of thyroid hormones.