MOLECULAR BIOLOGY OF GLYCOPROTEIN HORMONES

目前天然的人类垂体激素如促甲状腺激素 (TSH)只有有限的供应，这些制剂 可能被病理性病毒污染。 因此， 能够制备详细的生物化学，物理化学， 用这些制剂进行生物学或治疗研究。 此外，委员会认为， 控制垂体激素基因表达的因素有 不太了解。 我们最近克隆并测序了 完整的人类TSH-β亚基基因，并已部分确定 它的甲状腺激素调节区。 使用共转染 用人α亚基cDNA和人TSH- β基因组DNA，我们还生产了合成人类 垂体促甲状腺激素 虽然表面上含有更多的唾液酸 与天然TSH相比，这种合成TSH在体外具有同等活性， 将用于定义其他生物化学方面， 激素的治疗作用。 我们还计划定义其他 基因的调控区域，以深入了解 转录控制的基本机制。

Currently natural human pituitary hormones such as thyrotropin (TSH) are available in only limited supply and these preparations may be contaminated with pathologic viruses. Thus is has not been possible to prepare detailed biochemical, physicochemical, biologic or therapeutic studies with such preparations. Moreover, the factors controlling pituitary hormone gene expression are poorly understood. We have recently cloned and sequenced the complete human TSH-beta subunit gene and have partially defined its thyroid hormone regulatory region. Using cotransfection experiments with a human alpha subunit cDNA and human TSH- beta genomic DNA, we have also produced synthetic human pituitary TSH. Although apparently containing more sialic acid than natural TSH, this synthetic TSH is equally active in vitro and will be used to define additional biochemical aspects and therapeutic actions of the hormone. We also plan to define other regulatory regions of the gene to gain insight into the fundamental mechanisms of transcriptional control.