STRUCTURE AND FUNCTION OF PREGNANCY RECOGNITION HORMONE

绵羊母体对妊娠的识别依赖于 绵羊滋养层蛋白-1（oTP-1）。在第13天和 oTP-1代表孕体的主要分泌产物， 它负责抑制子宫前列腺素F2 α 分泌物oTP-1诱导的对细胞脉冲性分泌的抑制 前列腺素F2 α通过子宫允许维持体 持续分泌孕酮的黄体。猪和牛 孕体也显示出产生类似的抗黄体溶解 代理商，和人类等效已被假定以及。oTP-1具有 最近显示与α干扰素共享氨基酸同源性。 因此，oTP-1参与了孕体和胎盘之间的相互作用。 母体系统，导致适当的内分泌和 怀孕早期的免疫反应。 我们建议检查怀孕的结构/功能基础 识别和其他生物学效应的oTP-1使用合成的 肽的方法，用于直接受体竞争和产生 针对oTP-1和oTP-1合成肽的单克隆抗体。是 计划通过以下办法实现这一目标： (1)进行竞争性受体结合和功能实验 之间的合成肽和oTP-1，并确定能力， 与oTP-1受体结合的适当肽;特别强调 将被放置在使用较长的肽（可能的结构域）;（2） 通过系统性地修饰在受体竞争中重要的肽， 去除和/或取代氨基酸，以便更精确地 鉴定参与以下功能的oTP-1的序列或区域： (3)产生抗oTP-1的单克隆抗体，并测定其 阻断oTP-1与膜受体的功能和/或结合;（4）映射 这些单克隆抗体的表位特异性使用合成的 肽，其对应于oTP-1分子位于 表面;（5）使用合成肽产生位点特异性单克隆抗体 和多克隆抗体，并确定它们对功能的影响， 通过oTP-1的受体结合：（6）确定 表位，（因此不同区域）的oTP-1的竞争性结合 确定表位的单克隆抗体（及其Fab片段）之间 oTP-1的特异性。这些研究很重要，因为它们 将提供关于怀孕的结构基础的信息， 识别和oTP-1的抗病毒特性。

Maternal recognition of pregnancy in sheep is dependent upon secretion of ovine trophoblast protein-1 (oTP-1) by the conceptus. Between days 13 and 21 of pregnancy, oTP-1 represents the major conceptus secretory product, and it is responsible for inhibition of uterine prostaglandin F2alpha secretion. The oTP-1-induced inhibition of pulsatile secretion of prostaglandin F2alpha by the uterus allows for maintenance of the corpus luteum with continued secretion of progesterone. Porcine and bovine conceptuses have also been shown to produce similar antiluteolytic agents, and a human equivalent has been postulated as well. oTP-1 has recently been shown to share amino acid homology with alpha interferons. Thus, oTP-1 is involved in the interaction between the conceptus and maternal systems which results in appropriate endocrinological and immunological responses in early pregnancy. We propose to examine the structure/function basis for pregnancy recognition and other biological effects of oTP-1 using the synthetic peptide approach for both direct receptor competition and production of monoclonal antibodies to oTP-1 and oTP-1 synthetic peptides. It is planned that the objective be achieved through the following approach: (1) perform competitive receptor binding and functional experiments between synthetic peptides and oTP-1, and determine the ability of appropriate peptides to bind to the oTP-1 receptors; particular emphasis will be placed on the use of longer peptides (possible domains); (2) modify peptides that are important in receptor competition by systematic removal and/or substitution of amino acids in order to more precisely identify sequences or regions of oTP-1 that are involved in functions: (3) generate monoclonal antibodies to oTP-1 and determine their ability to block function and/or binding of oTP-1 to membrane receptors; (4) map the epitope specificity of these monoclonal antibodies using synthetic peptides that correspond to regions of the oTP-1 molecule located on the surface; (5) use synthetic peptides to produce site specific monoclonal and polyclonal antibodies and determine their effect on functions and receptor binding by oTP-1: (6) determine the steric relationship of epitopes, (and thus various regions) of oTP-1 by competitive binding between monclonal antibodies (and their Fab fragments) of defined epitope specificities with oTP-1. The proposed studies are important because they will provide information on the structural basis for pregnancy recognition and the antiviral properties of oTP-1.