Matzuk M M, Kornmeier C M, Whitfield G K, Kourides I A, Boime I
Department of Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110.
Mol Endocrinol. 1988 Feb;2(2):95-100. doi: 10.1210/mend-2-2-95.
TSH is a member of a family of heterodimeric glycoprotein hormones which have a common alpha-subunit but differ in their hormone-specific beta-subunit. To study the posttranslational processing and assembly of human TSH, eukaryotic expression vectors were constructed that contained either the human TSH beta gene only or both the TSH beta and alpha-genes. These vectors were transfected into Chinese hamster ovary cells and stable cell lines synthesizing TSH beta or TSH dimer were isolated. The kinetics of secretion of TSH beta and the rate of assembly of TSH dimer were compared to the known secretion and assembly of human LH and human CG. In the absence of the alpha-subunit, CG beta is secreted efficiently, but TSH and LH beta-subunits are slowly degraded intracellularly (t1/2 approximately equal to 6 h) and less than 10% is secreted into the medium. In the presence of the alpha-subunit CG beta was also secreted efficiently as dimer but only 50% of the LH beta appeared in the medium as LH dimer. However, unlike LH beta, the alpha-subunit efficiently combines with TSH beta since greater than 95% was secreted as TSH dimer. Thus, the determinants for human TSH beta secretion and assembly are unique from the other human glycoprotein hormone beta-subunits.
促甲状腺激素（TSH）是异源二聚体糖蛋白激素家族的一员，这些激素具有共同的α亚基，但激素特异性β亚基不同。为了研究人TSH的翻译后加工和组装，构建了真核表达载体，这些载体要么仅包含人TSHβ基因，要么同时包含TSHβ和α基因。将这些载体转染到中国仓鼠卵巢细胞中，并分离出合成TSHβ或TSH二聚体的稳定细胞系。将TSHβ的分泌动力学和TSH二聚体的组装速率与已知的人促黄体生成素（LH）和人绒毛膜促性腺激素（CG）的分泌和组装情况进行了比较。在没有α亚基的情况下，CGβ能有效分泌，但TSH和LHβ亚基在细胞内缓慢降解（半衰期约为6小时），不到10%分泌到培养基中。在有α亚基存在的情况下，CGβ也能作为二聚体有效分泌，但只有50%的LHβ以LH二聚体形式出现在培养基中。然而，与LHβ不同，α亚基能有效地与TSHβ结合，因为超过95%以TSH二聚体形式分泌。因此，人TSHβ分泌和组装的决定因素与其他人糖蛋白激素β亚基不同。
