BIOSYNTHESIS AND GLYCOSYLATION OF THYROTROPIN

重组人促甲状腺激素已生产后，短暂或稳定 将α和hTSH-β小基因转染到各种哺乳动物细胞中 包括中国仓鼠卵巢细胞。 碳水化合物组合物 分析表明，重组TSH具有比重组TSH更多的唾液酸。 常规垂体TSH，延迟其代谢清除率。 重组TSH的大规模生产已经通过使用 中空纤维生物反应器系统以及新的纯化方法。 通过修饰糖基化作用，也可产生各种TSH类似物 或蛋白质结构。 的具体作用 碳水化合物在促甲状腺激素的作用已经阐明了使用 差异糖基化亚基。 通过与Genzyme的合作研发协议 公司（波士顿），该公司和美国国立卫生研究院正在生产重组人 TSH用于甲状腺癌患者的临床研究。 批准 研究性新药申请和临床开始 预计1991年底将在美国国立卫生研究院和其他四个医学中心进行试验。

Recombinant human thyrotropin has been produced after transient or stable transfection of alpha and hTSH-beta minigenes into various mammalian cell lines, including Chinese hamster ovary cells. Carbohydrate composition analysis shows that the recombinant TSH has more sialic acid than conventional pituitary TSH, which delays its metabolic clearance rate. Large scale production of recombinant TSH has been achieved by employing a hollow fiber bioreactor system as well as novel methods of purification. Various analogues of TSH have also been produced by modifying glycosylation or protein structure using site-directed mutagenesis. The specific role of carbohydrate in the action of TSH has been elucidated by use of differentially glycosylated subunits. Through a Cooperative Research and Development Agreement with the Genzyme Corporation (Boston), the Company and NIH are producing recombinant human TSH for clinical studies in patients with thyroid cancer. Approval of the Investigational New Drug Application and the commencement of clinical trials at NIH and four other medical centers is expected in late 1991.