Thyrotropin Receptors in Brown Adipose Tissue: Thyrotropin Stimulates Type II Iodothyronine Deiodinase and Uncoupling Protein-1 in Brown Adipocytes*

Abstract

It has been demonstrated that TSH receptors are expressed not only in thyroid gland but also in extrathyroidal tissues. Brown adipose tissue of guinea pig has been reported to express TSH receptor messenger RNA (mRNA), but the physiological roles of TSH receptors in brown adipose tissue have not been understood. We studied the expression and function of TSH receptors in rat brown adipose tissue and cultured rat brown adipocytes. Northern analysis demonstrated the expression of TSH receptor mRNA in rat brown adipose tissue and cultured rat brown adipocytes. TSH receptor mRNA in rat brown adipose tissue was decreased by cold exposure of the rat, and its mRNA in cultured rat brown adipocytes was also decreased by incubation with TSH or (Bu)(2)cAMP. TSH increased the intracellular cAMP concentration in cultured rat brown adipocytes in a dose dependent manner. Type II iodothyronine deiodinase mRNA, its activity, and uncoupling protein-1 mRNA in cultured rat brown adipocytes were significantly increased by incubation with TSH in a dose-dependent manner. These results suggest the expression of functional TSH receptors in brown adipose tissue, which may be involved in regulation of the expression of type II iodothyronine deiodinase and uncoupling protein-1.

Change in Ucp1 mRNA Expression Following Long-Term Cold Exposure under Normal or High-Fat Diet Regimes in the Cold-Intolerant Mammal, Suncus murinus

“…Even when the period of high-fat diet was shorter, Ucp1 mRNA did not increase in the high-fat diet condition alone (WAHF) in contrast to the high-fat diet condition with cold. In addition, D2 mRNA, which is increased by a mechanism common to Ucp1 [7,16], did not increase significantly in WAHF. This may have been because the level of fat used in the high-fat group was relatively low, weakening the effect of increasing mRNA by a high-fat diet in the warm condition, or because the animals did not like the high-fat chow (ferret food), i.e., diet-induced thermogenesis via direct noradrenergic stimulation of BAT was not induced by overfeeding [1,19].…”

“…We then compared mRNA levels using Northern blot analysis because cold exposure and a high-calorie (carbohydrate and fat) diet are factors that bolster NST by activating Ucp1 mRNA expression which in turn activates the sympathetic nervous system via noradrenergic innervation of BAT [9,14,16,20,24,25,27,31,32]. In addition, we measured changes in mRNA of type II 5'-deiodinase (D2) in BAT, which is a critical enzyme that supplies local triiodothyronine (T 3 ) catalyzed from thyroxine (T 4 ) and rapidly increases upon cold exposure through the activation of the sympathetic nervous system via noradrenergic innervation of BAT [7,9,14,16], because local T 3 production is an effective factor for increasing Ucp1 in BAT [2,3].…”

“…However, we found that mRNA was increased by cold exposure only in the high-fat diet treatment (CAHF). A high-calorie diet is a factor that activates Ucp1 mRNA expression [9,14,16,24,25,30,31]. Even when the period of high-fat diet was shorter, Ucp1 mRNA did not increase in the high-fat diet condition alone (WAHF) in contrast to the high-fat diet condition with cold.…”

Effect of the presence of remnant thyroid tissue on the serum thyroid hormone balance in thyroidectomized patients

“…Moreover, in these reports, the postoperative serum TSH levels were increased compared to preoperative native levels or those of controls (7,8,9). It is possible that TSH stimulates both type 1 (D1) and type 2 (D2) deiodinases, which convert T 4 to T 3 mediated by a cAMP signaling pathway (11,12,13).…”

MECHANISMS IN ENDOCRINOLOGY: The crosstalk between thyroid gland and adipose tissue: signal integration in health and disease

“…The physiologic and pathologic roles played by activation of TSH receptor in white adipocytes remain a matter of investigation. The possibility was also investigated that TSH, by binding to its receptor on brown adipocytes, may stimulate thermogenesis, thus preventing an excessive drop in body temperature in hypothyroidism (54,55,56,57).…”