摘要
人甲状旁腺素(Parathyroid hormone,PTH)是由人甲状旁腺主细胞分泌的直链肽,含84个氨基酸,是维持体内钙磷平衡的主要激素。PTH通过识别骨骼、小肠和肾脏等细胞表面特异性受体,与降钙素和维生素D共同调节Ca2+,PO43-的代谢,具有明显的成骨作用。研究发现,PTH的N-端34肽(PTH 1-34)具有完全的PTH受体结合能力与生物活性。目前PTH 1-34作为临床治疗骨质疏松症的注射剂已在美国上市,但价格昂贵且需要每天注射给药。而国内关于PTH1-34的临床研究很少,所以有必要通过基因工程手段获取PTH 1-34,降低成本并可大规模制备目的蛋白。本文概述了PTH近年来在国内外的研究情况,利用目前发展较快的毕赤酵母真核表达系统,构建了高效表达PTH 1-34毕赤酵母工程菌。为今后上发酵罐摸清条件。
Parathyroid hormone （PTH） is secreted by parathyroid cell, and it is a kind of straight-chain peptide with 84 amino acids. PTH is the capital hormone to retain the balance of calcium and phosphor. PTH can regulate the metabolism of Ca^2＋, PO4^3- with Calcitionin and Vitamin D by recognizing the specific receptors which are on the surface of bone cell, small intestine cell and kidney cell. By researching we found the N-terminal fragment amino acids 1-34 （PTH 1-34） can play all function of PTH. Now PTH 1-34 has been approved by FDA in USA as a new class of drugs to treat osteoporosis. Whereas it is so expensive and needed everyday, and the domestic clinical study is very few. So it is necessary to adopted gene engineering technology to generate PTH 1-34 in order to reduce the high cost and gain generous protein production. The reported study of PTH and the characteristics of eukaryocyte expression system-Pichia Pastoris system were reviewed in this article to construct the recombinant yeast expression system with PTH 1-34.
