3.甲状腺ホルモン作用

The action of a hormone to the organism can be generally considered in two fashions : the mechanism of its action and its physiological action. The mechanism of the action should include a primary event caused by the hormone in the target cell, followed by a series of successive reactions. The physiological action is composed of functions of the target organ, which are maintained or stimulated by the hormone sercreted or administered. In the strict sense, the mechanism of thyroid hormone action remains obscure though the physiological action implicates stimulations of their growths, maturations and basal metabolic rates, which indicate extensive changes in carbohydrate, lipid and protein metabolisms. The characteristic features of thyroid hormone action are as follows : first, the hormone affects almost all organs except brain, gonads and accessary reproductive organs, secondly, the hormone needs some length of time (the latent period) to exert the apparent action after its administration and thirdly, an optimal dose of the hormone is requeird to maintain the euthyroid state of the organism or to recover it to the normal level. Recently accumulated observations on the effects of minute amounts of thyroid hormone injected to hypothyroid animals were surveyed. Early and marked stimulations by the hormone administration are as follows : liver mitochondria respiration (State 4), synthesis of nuclear and cytoplasmic RNA (mainly r-RNA), RNA polymerase activity, synthesis of membrane phospholipid, incorporation of amino acid into protein by mitochondria and microsome and synthesis of respiratory enzymes which resulted in increased oxygen consumption.<BR>In the connection with the first point, thyroid hormone may act on the target organs directly or indirectly because they affect each other (organ correlation). Among them, a reciprocal interrelationship (a feed back regulation) exists exceptionally between thyroid and adenohypophysis whose oxygen consumption was suppressed by thyroid hormone while stimulated after thyroidectomy. Since 1966, Tonoue and Yamamoto in this laboratory, have made a series of experiments to disclose the mechanism and found that thyroidectomy stimulated α-aminoisobutyric acid transport of rat adenohypophysis and 20 μg T₄ per 100 g body weight injected to thyroidectomized rats suppressed the augmented amino acid transport capacity. A similar finding was also made of experiments on ¹⁴ "C-alanine incorporation into the total protein of the adenohypophysis. Change in the ¹⁴C-alanine incorporation in the thyroid states was distinctly observed in TSH rich granules. The levels of free amino acids in rat adenohypophysis did not change or decrease with a few exception, that is, isoleucine, leucine and proline after thyroidectomy. Adenohypophyses from normal, thyroidectomized and thyroidectomized-and T₄ injected rats were incubated in KRB with ³'H-Phe and ¹⁴C-Arg. Triton X 100 (1%) extracts of the adenohypophyses were analysed with the use of disc electrophoresis. Thyroidectomy decreased markedly growth hormone and prolaction contents. While T₄ injection increased not only growth hormone and prolaction contents but also stimulated ³H-Phe and ¹⁴C-Arg incorporation rates into growth hormone and prolaction. The stimulations were clearly observable 12 hr after T₄ injection. Proteins separated between top of the gel and growth hormone area increased after thyroidectomy and T¹⁴ injection stimulated accumulation of the proteins. After thyroidectomy, marked changes were observed in carbohydrates metabolism of adenohypophysis, that is, increased output of ¹⁴CO₂ from 1-¹⁴C-glucose, decreased formation of lactic acid from glucose and increased glucose consumption followed by increase of leucine incorporation into the total protein.