Impaired metabolic response to nerve stimulation in brown adipose tissue of hypothyroid rats

In brown adipose tissue of the rat, chemically or surgically induced hypothyroidism caused the following effects. A large decrease of the magnitude of the metabolic response to electrical nerve stimulation. The deactivation half-time of the response was reduced to 70% of the control value, with no change in catechol O-methyltransferase activity. Pre-incubation of tissues with norepinephrine, 10(-5) M, increased the response to subsequent nerve stimulation almost to that of the controls. The catecholamine analogue dose-response curves were shifted to the right. The shift was very pronounced for isoproterenol (K50 426 nM versus 2 nM), somewhat less marked for norepinephrine (7373 nM versus 194) and very slight for phenylephrine (2803 nM versus 1649); there was almost no change in Emax values. An increase of octanoate oxidative capacity. A decrease of the capacity of the stereoselective binding of (-)-[3H]dihydroalprenolol of the high-affinity (Kd 2.0 nM) sites to a fourth of the control value and an increase by a factor of 2.9 of the Kd of the low-affinity binding sites. This decrease of binding to the beta-receptors was not sufficient quantitatively to explain the decrease in the metabolic response, suggesting the existence of an additional defective reaction which could occur between the binding to the beta-receptors and the activation of the triglyceride lipase. These results show that the sharp decrease of the metabolic response of brown adipose tissue to nerve stimulation has multiple causes. The findings are discussed in the context of the drastic decrease of cold resistance in hypothyroid rats.