Action mechanism of thyroid stimulating hormones (TSH and LATS)

Abstract

TSH stimulates the secretion and synthesis of thyroid hormone, and also stimulates many metabolic pathways i.e, salt and water, carbohydrate, phosphorus and phospholipid, nucleic acid, amino acid and protein metabolism. Evidence has been accumulated that LATS causes a prolong effect on the thyroid and LATS differs in several respects from TSH. Until now the precise role of TSH and LATS at cellular level has not been known and the mode of action of two substances is not clear.In this paper, the metabolic effects of TSH and LATS on the thyroid were examined extensively using both in vitro and in vivo systems. The incorporation of 32P into the thyroid gland after a single injection of LATS and TSH was increased about 2 fold in the thyroxine treated mice. Also specific activities of RNA and phospholipid in the gland were increased remarkably. Experiments using 3H-uridine, TSH and LATS increased the incorporated radioactivity per RNA.A single injection of TSH or LATS into mice falied to stimulate the incorporation of 3H-leucine into thyroidal protein. While the continuous injection of LATS for 5 days caused increased thyroid weight, augmented protein content and increased incorporation of 3H-leucine. Also the specific activity of incorporated radioactivity per mg thyroid protein was significantly increased. Treatment with LATS or TSH for 8 days produced marked goiter formation accompanied by a high I131 thyroidal uptake. LATS stimulates protein synthesis in the gland, as does TSH.Using McKenzie's method, cyclic 3′5′ AMP (C 3′ 5′ AMP) and Dibutyryl cycilic 3′ 5′ AMP (D.C 3′ 5′ AMP) were found to increase thyroid hormone release from mouse thyroid in vivo. Other adenine nuclectides were also active. Simultaneous injection of theophylline and caffeine with C 3' 5' AMP and D.C 3′ 5′ AMP augmented the stimulatory effect of these adenine nucleotides on hormone release, although theophylline or caffeine had only a slight effect alone. No effect was obtained by the injection of NaF with D.C 3′ 5′ AMP. These adenine nucleotides have no enhancing action on hormone release from mouse thyroids during in vitro incubations, and no stimulatory effects were obtained by the nucleotides on the hydrolysis of thyroglobulin in mouse thyroid homogenates. These adenine nucleotides appeared to have no direct action on the enzyme participating in the breakdown of thyroglobulin.According to Pastan's method, the effect of TSH on cyclase activity was determined using beef and rabbit thyroid homogenate, but the increase of cyclic AMP synthesis from 3H-ATP (or 14C-ATP) was not obtained by the large doses of TSH. Similarly also LATS haven't any stimulating action on adenyl cyclase activity. NaF did not elevate adenyl cyclase activity, but inhibited ATP destruction by the inhibition of ATPase. Theophylline inhibited cyclic AMP destruction significantly. Using beef thyroid slices, 3H-adenine was preincubated for 1 hr and then TSH (Armour or NIH) or LATS was incubated for 30 min. with theophylline or NaF. The incorporated radioactivity into cyclic AMP in whole thyroid slice was examined. TSH and LATS similarly stimulated the incorporation of 131H-adenine into cyclic AMP in beef thyroid slice, especially in the presence of theophylline. However, the stimulatory effect of NaF on cyclic AMP formation was very slight.Both TSH and LATS elevated cyclic AMP levels in the gland, however it may be some of effects of both these thyroid stimulator. It is possible that TSH and LATS have similar stimulating action on various metabolism in the thyroid.