Evolutionary Biology of Prolactins and Somatotropins

这项研究将确定某些荷尔蒙的哪些结构特征可能与它们的生物活性有关。拟研究的激素有催乳素(PRL)、生长激素(GH)及相关蛋白胎盘催乳素。激素片段将通过化学和酶裂解制备，并将使用来自不同器官的膜制剂来测试它们的受体结合活性。同样的问题将用不同的方法来解决。这些被认为具有重要功能的激素片段将使用定点突变技术进行检测。此外，一种激素(如催乳素)的这些片段中的氨基酸将被另一种激素(即生长激素)的同一片段中的氨基酸所取代。然后将对突变的分子进行受体结合和生物活性测试。这些激素与正常和不正常的生长有关。有关其结构特征的信息将有助于生产能够阻止其作用或增强生物活性的类似物。

The research will determine which structural features of certain hormones can be related to their biological activities. The hormones to be studied are prolactin (PRL), and growth hormone (GH), and the related protein placental lactogen. Fragments of the hormones will prepared by chemical and enzymatic cleavage and they will be tested for receptor binding activity using membrane preparations from various organs. The same question will be addressed using a different approach. Segments of these hormones that are thought to be of functional significance will be detected using the techniques of site specific mutagenesis. In addition, the amino acids in such segments of one kind of hormone (e.g. a PRL) will be replaced by he amino acids in the same segment of the other kind of hormone (i.e. GH). The mutant molecules will then be tested for receptor binding and biological activities. These hormones are involved in both normal and abnormal growth. Information on their structural features will be of value in producing analogue that can block their action or that have enhanced biological activities.