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Some signs of hyperthyroidism, including enhanced responses to external stimulation and elevation of basal metabolic rate, are reminiscent of increased sympathetic activity. The possibility has been raised that the action of thyroid hormones is mediated through catecholamines. 1 2 Furthermore, hypothyroid- ism is associated with depressed sympathetic responses to catecholamines. 3The possibility that the thyroid hormones increase the rate of norepinephrine (NE) synthesis is not supported by a recent study from this laboratory showing that the turnover rate of cardiac NE is the same in normal and hyperthyroid mice. 4Published reports indicate that the exposure of hyperthyroid rats to cold or the injection of these animals with catecholamines elicits an exaggerated rise in plasma FFA. 5 In contrast, the responses to these stimuli are greatly diminished in thyroidectomized rats but are restored by treatment of the animals with thyroid hormones. Similarly, epinephrine elicits an exaggerated lipolytic response on incubation xith epididymal fat pads from hyperthyroid rats, while the cate- cholamine elicits almost no response from fat pads of hypothyroid rats. 6-8Again the lipolytic response is restored if the adipose tissue is taken from hypo- thyroid rats after treatment with thyroid hormone. Since NE, epinephrine, isoproterenol, and corticotropin, added to adipose tissue in vitro, all stimulate lipolysis to almost the same maximum degree, 9' 10 it is generally assumed that the rate of this process is limited by the amount of lipase in adipose tissue. Thyroxine is usually thought to enhance the lipolytic effects of catecholamines by increasing the amount of catecholamine-sensitive lipase in adipose tissue. 6Recent findings from this laboratory'1 12 have demonstrated that the total lipase activity of adipose tissue is much higher than heretofore considered. This conclusion is based on experiments showing that NE in high concentrations induces only a fraction of the lipolytic response produced when phosphodiesterase is blocked by high concentrations of theophylline. From these results it was inferred that the maximal effects of theophylline are caused by a rise in cyclic 3', 5'-AXIP to a level that completely activates lipase, while the effects of NE are limited by the level of cyclic 3',. 5'-A1 produced when adenyl cyclase is completely activated. The present study concerns the effects of theophylline and norepinephrine in adipose tissue from hypothyroid, hyperthyroid, and euthyroid rats. The results support the hypothesis that thyroxine enhances the action of catecholamines on the lipolytic system by increasing the amount of adenyl cyclase and not by in- creasing the total lipase activity. Materials and Methods. -Experiments were carried out on male Sprague-Dawley rats. Animals were made hyperthyroid by injection of 1-thyroxine (1 mg/kg s. c. ) each day for
Krishna et al. (Fri,) studied this question.