小鼠垂体促甲状腺肿瘤细胞在体外过量产生游离α亚基。

Excess production of free alpha subunits by mouse pituitary thyrotropic tumor cells in vitro.

作者信息

Blackman M R, Gershengorn M C, Weintraub B D

出版信息

Endocrinology. 1978 Feb;102(2):499-508. doi: 10.1210/endo-102-2-499.

Abstract

Primary cultures from three serially transplanted mouse pituitary thyrotropic tumors, Furth 97A, 97B, and 97C, and one newly generated tumor, NIH 101A, were shown to secrete free alpha subunits and a beta subunit (TSH-beta) in addition to intact TSH. The three glycopeptides were measured in specific, heterologous radioimmunoassays. Basal secretion of alpha subunit was found to be in excess in all four thyrotropic tumor cultures, ranging from 5.7- to 8.9-fold higher than that of intact TSH and 30- to 35-fold higher than that of free TSH-beta. In cultures from 97A, TRH (10(-7) M) stimulated the secretion of TSH, alpha subunit, and TSH-beta by 175-185% and (T4, 10(-5) M) inhibited TSH to 19%, alpha subunit to 68%, and TSH-beta to 58% of control. Secretion of TSH and its subunits in cultures from 97B was not consistently affected by TRH or T4. In cultures from 97C, TSH and alpha secretion was inhibited in a dose-dependent fashion by T3 from 2.5 x10(-9) to 1.6x10(-7) M. Gel chromatography of incubation media from tumor 97A revealed elution volumes of TSH and alpha similar to those of purified rat glycopeptides and confirmed the excess secretion of free alpha subunit. In contrast, the alpha to TSH ratios in media from cultures of pituitary cells from normal and thyroidectomized rats were 1.6 and 0.8, respectively. The total production of TSH and its subunits was measured in cultures from tumor 97A and confirmed that alpha subunit was synthesized excessively. The ratio of the plasma concentrations of alpha to TSH in tumor-bearing mice was 1.6 compared to 1.3 in thyroidectomized mice, and 0.36 in thyroidectomized rats. The alpha to TSH ratios in extracts of the corresponding thyrotropic tissues (tumor or pituitary) were 2.7, 1.7, and 0.40, respectively. These data are analogous to those reported in humans with thyrotropic and certain other pituitary tumors, and support hypothesis that the subunits of glycoprotein hormones are independently synthesized.

摘要

来自三只经连续移植的小鼠垂体促甲状腺肿瘤（Furth 97A、97B和97C）以及一个新生成的肿瘤（NIH 101A）的原代培养物，除了完整的促甲状腺激素（TSH）外，还分泌游离的α亚基和β亚基（TSH-β）。通过特异性的异源放射免疫测定法对这三种糖肽进行了检测。发现在所有四种促甲状腺肿瘤培养物中，α亚基的基础分泌均过量，比完整TSH的基础分泌高5.7至8.9倍，比游离TSH-β的基础分泌高30至35倍。在来自97A的培养物中，促甲状腺激素释放激素（TRH，10⁻⁷ M）使TSH、α亚基和TSH-β的分泌增加了175%至185%，而甲状腺素（T4，10⁻⁵ M）则使TSH分泌降至对照的19%，α亚基降至68%，TSH-β降至58%。来自97B的培养物中TSH及其亚基的分泌并未受到TRH或T4的持续影响。在来自97C的培养物中，三碘甲状腺原氨酸（T3，浓度从2.5×10⁻⁹至1.6×10⁻⁷ M）以剂量依赖的方式抑制TSH和α亚基的分泌。对肿瘤97A的培养液进行凝胶色谱分析，结果显示TSH和α亚基的洗脱体积与纯化的大鼠糖肽相似，证实了游离α亚基的过量分泌。相比之下，正常大鼠和甲状腺切除大鼠垂体细胞培养物培养液中的α亚基与TSH的比值分别为1.6和0.8。对肿瘤97A的培养物中TSH及其亚基的总产量进行了测定，证实α亚基合成过量。荷瘤小鼠血浆中α亚基与TSH的浓度比为与甲状腺切除小鼠的该比值为1.3，甲状腺切除大鼠的该比值为0.36。相应促甲状腺组织（肿瘤或垂体）提取物中的α亚基与TSH的比值分别为2.7、1.7和0.40。这些数据与在患有促甲状腺肿瘤和某些其他垂体肿瘤的人类中所报道的数据相似，并支持糖蛋白激素亚基是独立合成的这一假说。