Alpha 1- and beta-adrenergic receptors in brown adipose tissue and the adrenergic regulation of thyroxine 5'-deiodinase.

The density of alpha 1- and beta-adrenergic receptors and the adrenergic regulation of the type II thyroxine 5'-deiodinase were investigated in brown adipose tissue. The density of the alpha 1- and beta-adrenergic receptors was determined in membranes of brown fat from animals in different physiological states, i.e. in cold-acclimated, neonatal, cafeteria-fed, genetically obese and hypothyroid animals. The density of the alpha 1-adrenergic receptors in brown fat correlated well with the recruitment state of the tissue: the receptor density was increased when the brown fat was recruited and decreased when the brown fat was atrophied. The density of the beta-adrenergic receptors did not correlate with the recruitment state. The regulation of the conversion of thyroxine (T4) to triiodothyronine (T3) by type II 5'-deiodinase in vitro was investigated in brown adipocytes from euthyroid and hypothyroid rats. alpha 1- and beta-adrenergic stimulation enhanced the activity of the 5'-deiodinase in a synergistic way. The primary signal seemed to be beta-adrenergic stimulation and cyclic AMP, whereas the role of the alpha 1-adrenergic receptors was a potentiation of the cyclic AMP effect via Ca2+ and protein kinase C. The maximal response of the 5'-deiodinase needed all these three different signals. Synergistic potentiation of the beta-adrenergic stimulation by alpha 1-adrenergic stimulation was seen especially in brown adipocytes from hypothyroid rats. Also the normal stimulation of the 5'-deiodinase activity as such was enhanced due to hypothyroidism. The role of synergism was investigated further in cell respiration (oxygen consumption) and cyclic AMP accumulation. In brown adipocytes from hypothyroid rats, the beta-adrenergic respiration was potentiated by alpha 1-adrenergic stimulation. An inhibitory effect of the alpha 1-adrenergic antagonist prazosin was found even in the cyclic AMP accumulation in brown adipocytes of hypothyroid rats, although no significant synergism could be demonstrated. It was suggested that the increased density of the alpha 1-adrenergic receptors may be of significance for nonshivering thermogenesis in certain physiological situations (e.g. in cold acclimation) via two different but synergistic mechanisms, i.e. the regulation of thyroxine 5'-deiodinase and of adenylate cyclase.