Thyroid-stimulating activity of chorionic gonadotropin and luteinizing hormone.

Thyroid-stimulating activity of chorionic gonadotropin and luteinizing hormone.
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绒毛膜促性腺激素和黄体生成素的甲状腺刺激活性。

DOI:
10.1210/jcem-47-4-855
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发表时间:
1978
期刊:
The Journal of clinical endocrinology and metabolism
影响因子:
--
通讯作者:
B. Nisula
B. Nisula
中科院分区:
--
文献类型:
--
作者:
G. Taliadouros;R. Canfield;B. Nisula

文献摘要

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虽然最近的证据表明hCG分子具有内在的促甲状腺活性(TSA),但尚不清楚除hCG外的促甲状腺分子是否在粗的或高度纯化的hCG中有一些明显的TSA。为了确定在hCG纯化过程中是否从粗尿hCG中排除促甲状腺因子,测定了用于hCG制备的起始材料以及高度纯化的hCG制剂中的间质细胞刺激活性(ICSA)与TSA的比值。这两种生物活性的比例在纯化过程中没有明显变化,这表明除了hCG本身之外,没有其他因素存在于粗hCG中。在Sephadex G-100上对高纯度hCG进行凝胶过滤,并将主蛋白峰分成三个部分。各组分中TSA与ICSA的比值相同,进一步表明这些活性是同一分子固有的。如果hCG具有固有的促甲状腺活性,正如这些数据所表明的那样,那么促甲状腺活性可能是LH的次生生物活性,因为LH和hCG在结构和功能上有很强的相似性。为了评估LH分子对固有TSA的影响,通过重组具有最小TSH免疫反应性的亚基,制备了具有最小TSH污染的LH制剂。由高度纯化的hCG α和羊LH β亚基重组形成的LH分子在生物测定中显示的TSA比基于免疫反应性TSH污染的预期高25倍。没有证据支持除hCG外的促甲状腺因子存在于粗制或高纯化的hCG制剂中。我们的研究发现,结构类似hCG的混合LH分子具有强ICSA,也表现出固有的TSA,进一步扩展并支持了TSA是hCG分子固有特性的假设。
While recent evidence indicates that the hCG molecule has intrinsic thyroid-stimulating activity (TSA), it is not clear whether a thyrotropic molecule other than hCG accounts for some of the TSA apparent in the crude or highly purified hCG. To determine if a thyrotropic factor is excluded from crude urinary hCG during purification of hCG, the ratio of interstitial cell-stimulating activity (ICSA) to TSA was determined in the starting material used for hCG preparation as well as in the highly purified hCG preparation. The ratio of the two biological activities did not change significantly during purification, suggesting that no factor present in crude hCG other than hCG itself accounts for the TSA. The highly purified hCG preparation was gel-filtered on Sephadex G-100 and the main protein peak was divided into three fractions. The ratio of TSA to ICSA was the same in each fraction, further indicating that these activities are intrinsic to the same molecule. If hCG has intrinsic thyrotropic activity, as these data indicate, then thyrotropic activity would be expected to be a secondary biological activity of LH, since there are strong structural and functional similarities between LH and hCG. In order to assess the LH molecule for intrinsic TSA, an LH preparation with minimal TSH contamination was prepared by recombining subunits exhibiting minimal TSH immunoreactivity. The LH molecule formed from the recombination of highly purified hCG alpha and ovine LH beta subunits exhibited TSA in the bioassay that was 25 times greater than that expected based on the immunoreactive TSH contamination. There was no evidence to support the existance of a thyrotropic factor other than hCG in either crude or highly purified hCG preparations. Our finding that a hybrid LH molecule structurally similar to hCG with potent ICSA also exhibits intrinsic TSA further extends and supports the hypothesis that TSA is an intrinsic property of the hCG molecule.