Brenner-Gati L, Trowbridge J M, Moucha C S, Gershengorn M C
Department of Medicine, Cornell University Medical College, New York, New York 10021.
Endocrinology. 1990 Mar;126(3):1623-9. doi: 10.1210/endo-126-3-1623.
We reported that TSH, which stimulates cAMP accumulation and proliferation of FRTL-5 thyroid cells, chronically increases the 1,2-diacylglycerol (1,2-DG) content of FRTL-5 cells. Because activation of inositol lipid hydrolysis by a phospholipase-C enzyme would generate 1,2-DG, we compared the effects of TSH on inositol lipid metabolism to TSH-induced increases in 1,2-DG content and stimulation of cAMP accumulation and cell growth. Acute stimulation of inositol lipid hydrolysis did not occur with doses of 1000 microU/ml or lower, but did occur with TSH doses of 3000 microU/ml and higher, with rates between 1-4%/h. More importantly, in cells chronically exposed to TSH, the rate of inositol lipid hydrolysis was increased only at TSH doses of 10,000 microU/ml or greater, and the maximum rate was 4-5%/h. When cells were growth arrested by TSH deprivation, there was no change in the content of inositol phosphates or polyphosphoinositides. In contrast to the high doses of TSH required to stimulate inositol lipid hydrolysis, TSH-induced elevation of 1,2-DG content and stimulation of cAMP accumulation and growth occurred at physiological TSH concentrations, with minimal effective doses in the range of 1-10 microU TSH/ml, and half-maximally effective doses between 50-200 microU TSH/ml. These data suggest that inositol lipid hydrolysis does not mediate the proliferative response to TSH in FRTL-5 cells and is not the mechanism by which increases in 1,2-DG content occur at physiological TSH concentrations.
我们曾报道，促甲状腺激素（TSH）可刺激FRTL-5甲状腺细胞中cAMP的积累及细胞增殖，并能长期增加FRTL-5细胞中1,2 -二酰甘油（1,2 - DG）的含量。由于磷脂酶C可激活肌醇脂质水解并生成1,2 - DG，我们比较了TSH对肌醇脂质代谢的影响与TSH诱导的1,2 - DG含量增加以及对cAMP积累和细胞生长的刺激作用。1000微单位/毫升及以下剂量的TSH不会引起急性肌醇脂质水解，但3000微单位/毫升及以上剂量的TSH会引起肌醇脂质水解，水解速率在1 - 4%/小时之间。更重要的是，在长期暴露于TSH的细胞中，仅在10000微单位/毫升及以上剂量的TSH作用下，肌醇脂质水解速率才会增加，最大速率为4 - 5%/小时。当细胞因TSH剥夺而生长停滞时，肌醇磷酸酯或多磷酸肌醇的含量没有变化。与刺激肌醇脂质水解所需的高剂量TSH相反，TSH诱导的1,2 - DG含量升高以及对cAMP积累和生长的刺激作用在生理TSH浓度下即可发生，最小有效剂量范围为1 - 10微单位TSH/毫升，半最大有效剂量在50 - 200微单位TSH/毫升之间。这些数据表明，肌醇脂质水解并不介导FRTL-5细胞对TSH的增殖反应，也不是在生理TSH浓度下1,2 - DG含量增加的机制。
