Richman R, Park S, Akbar M, Yu S, Burke G
Endocrinology. 1975 Jun;96(6):1403-12. doi: 10.1210/endo-96-6-1403.
We studied the effects of TSH on rat thyroid ornithine decarboxylase (ODC) activity. After 1 day of goitrogen treatment, there was an abrupt fall in serum triiodothyronine (T3) a rise in circulating TSH, and a dramatic increase in thyroid ODC activity. Despite the continued rise in TSH and progressive increase in thyroid gland size with further treatment, thyroid ODC activity declined on the third day and remained at submaximal levels. Thyroid ODC activity was also stimulated in a dose-related manner by administration of exogenous TSH. Little TSH effect was noted before 3 h. Maximal ODC activity occurred between 4 and 5 h. The TSH stimulation of ODC could be inhibited by pretreatment with actinomycin D or cycloheximide, suggesting that the increase in ODC activity requires new RNA and protein synthesis. Although pretreatment with agents that alter microtubule structure (e.g., colchicine and vinblastine) prevent stimulation of ODC activity by TSH, additional data suggest, but do not confirm, that hrmone secretion and ODC activation may be dissociable. Further studies were undertaken to determine whether cyclic AMP (cAMP) or prostaglandins played any role in the regulation of thyroidal ODC activity. Dibutyryl cAMP, alone, or together with aminophylline, did not stimulate thyroidal ODC activity in dosages which concomitantly stimulated adrenal enzyme activity. Likewise, prostaglandin E2 (PGE2) did not stimulate thyroidal ODC activity, but did stimulate adrenal enzyme activity in a dose-related manner. However, pre-treatment of rats with inhibitors of prostaglandin synthesis prevented the activation of thyroidal ODC BY TSH. One inhibitor, indomethacin, attenuated the TSH stimulation of enzyme activity in a dose-related manner. Indomethacin pretreatment also resulted in approximately a 10-fold decrease in thyroidal prostaglandin levels. Exogenous PGE9, in dosages as high as 500 pg, did not overcome the inhibitory effect of indomethacin on ODC activation. Although the precise role for endogenous prostaglandins remains to be defined, it does appear that a reduction in thyroidal prostaglandins prevents activation of the enzyme by TSH.
我们研究了促甲状腺激素（TSH）对大鼠甲状腺鸟氨酸脱羧酶（ODC）活性的影响。给予致甲状腺肿药物1天后，血清三碘甲状腺原氨酸（T3）急剧下降，循环中的TSH升高，甲状腺ODC活性显著增加。尽管随着进一步治疗TSH持续升高且甲状腺体积逐渐增大，但甲状腺ODC活性在第三天下降并维持在次最大水平。给予外源性TSH也能以剂量相关的方式刺激甲状腺ODC活性。在3小时之前未观察到明显的TSH效应。最大ODC活性出现在4至5小时之间。放线菌素D或环己酰亚胺预处理可抑制TSH对ODC的刺激，这表明ODC活性的增加需要新的RNA和蛋白质合成。虽然用改变微管结构的药物（如秋水仙碱和长春碱）预处理可阻止TSH对ODC活性的刺激，但其他数据表明（但未证实）激素分泌和ODC激活可能是可分离的。我们进行了进一步研究以确定环磷酸腺苷（cAMP）或前列腺素是否在甲状腺ODC活性调节中起任何作用。单独的二丁酰cAMP或与氨茶碱一起，在能同时刺激肾上腺酶活性的剂量下，并未刺激甲状腺ODC活性。同样，前列腺素E2（PGE2）也未刺激甲状腺ODC活性，但能以剂量相关的方式刺激肾上腺酶活性。然而，用前列腺素合成抑制剂预处理大鼠可阻止TSH对甲状腺ODC的激活。一种抑制剂吲哚美辛能以剂量相关的方式减弱TSH对酶活性的刺激。吲哚美辛预处理还导致甲状腺前列腺素水平降低约10倍。高达500 pg剂量的外源性PGE9并未克服吲哚美辛对ODC激活的抑制作用。尽管内源性前列腺素的确切作用仍有待确定，但甲状腺前列腺素的减少似乎确实会阻止TSH对该酶的激活。
