Taskasu N, Sato S, Tsukui T, Yamada T, Miyakawa M
J Clin Endocrinol Metab. 1976 Jul;43(1):69-79. doi: 10.1210/jcem-43-1-69.
Possible differences of the mode of action of TSH and prostaglandin E1 (PGE) on the synthesis of cyclic AMP were studied in normal human thyroids (normal thyroid) and thyroids from thyrotoxic patients (toxic thyroid). TSH was less effective in toxic thyroids than in normal thyroids; whereas PGE1 was equally effective in normal thyroids and toxic thyroids. Since the basal level of cyclic AMP was the same in normal and toxic thyroids, this lower sensitivity of toxic thyroids to TSH was not due to the fact that toxic thyroids were already overactive in terms of cyclic AMP synthesis. The measurement of adenylate cyclase and phosphodiesterase activities in the plasma membranes or homogenates failed to explain this lower sensitivity of toxic thyroids to TSH. Small and large doses of T4 and T3 failed to suppress an increase of cyclic AMP produced by PGE1, in the slices and plasma membranes of normal and toxic thyroids; whereas large doses of T3 depressed an increase of cyclic AMP in response to TSH in the thyroid plasma membrane of toxic thyroids. When both TSH and PGE1 were administered simultaneously, an additive increase of cyclic AMP was found in normal thyroids and in toxic thyroids. From the data accumulated, we suggest that, although TSH and PGE1 stimulate cyclic AMP synthesis in normal and toxic thyroids, the site of action and/or mode of action of these two stimulators may possibly be different, at least in human thyroids.
在正常人甲状腺(正常甲状腺)和甲状腺毒症患者的甲状腺(毒性甲状腺)中,研究了促甲状腺激素(TSH)和前列腺素E1(PGE)对环磷酸腺苷(cAMP)合成的作用方式可能存在的差异。TSH对毒性甲状腺的作用比对正常甲状腺的作用小;而PGE1在正常甲状腺和毒性甲状腺中的作用效果相同。由于正常甲状腺和毒性甲状腺中cAMP的基础水平相同,毒性甲状腺对TSH的这种较低敏感性并非由于毒性甲状腺在cAMP合成方面已经过度活跃。对质膜或匀浆中腺苷酸环化酶和磷酸二酯酶活性的测定未能解释毒性甲状腺对TSH的这种较低敏感性。小剂量和大剂量的T4和T3均未能抑制正常甲状腺和毒性甲状腺切片及质膜中PGE1所产生的cAMP增加;而大剂量的T3可抑制毒性甲状腺质膜中TSH所引起的cAMP增加。当同时给予TSH和PGE1时,在正常甲状腺和毒性甲状腺中均发现cAMP有相加性增加。根据积累的数据,我们认为,尽管TSH和PGE1均可刺激正常甲状腺和毒性甲状腺中cAMP的合成,但这两种刺激物的作用位点和/或作用方式可能不同,至少在人类甲状腺中是这样。