ROLE OF INHIBIN AND FRP PROTEINS IN ERYTHROPOIESIS

总的目标是调查最近两个 纯化的蛋白质在人类红细胞生成中的作用。 抑制素a 选择性抑制分泌的促垂体激素 卵泡刺激素（FSH），已被定性为 由α和β多肽组成的异二聚体蛋白质。 FSH释放蛋白（FRP）显示为二聚体，由以下组成： 两条甜菜碱β链 有人建议，它们可以构成 一种新的体液调节控制红细胞生成涉及两个 蛋白质二聚体具有功能上相反的效果。 基于我们 最近的研究结果表明，它们对红细胞分化的影响， 建议进行以下分析，以深入了解它们的作用 在人类红细胞生成中。 1. 为了进一步表征FRP和纤维增强塑料对 类红细胞祖细胞：它们的剂量反应，依赖于 促红细胞生成素和特异性。 的可能依赖性 观察到的对辅助细胞的影响将通过使用细胞 消耗和重建实验，并通过使用富集 低细胞密度的骨髓祖细胞。 此外，可能的 还将通过使用无血清骨来分析对血清的依赖性 骨髓培养 2. 为了确定FRP效应的谱系特异性， 通过探索它们对其他祖细胞的影响， 造血谱系以及它们可能的协同或 与各种重组因子的拮抗相互作用。 3. 为了鉴定表达FRP和/或BMP 2的细胞类型， S1核酸酶分析和RNA原位杂交。 的 将检查生产的FRP/垃圾箱的功能实体， 生物测定和放射免疫测定。 4. 研究观察到的效应的作用机制 通过检测其对细胞增殖的影响， 骨髓红系祖细胞及其与 K562细胞的表面受体。

The overall objective is to investigate the role of two recently purified proteins in human erythropoiesis. Inhibin, a hypophysiotropic hormone which selectively suppresses the secretion of follicle-stimulating hormone (FSH), had been characterized as a heterodimeric protein consisting of alpha- and beta-polypeptides. FSH releasing protein (FRP) was shown to be a dimer consisting of two inhibin beta-chains. It is proposed that they may constitute a new humoral regulatory control for erythropoiesis involving two protein dimers with functionally opposite effects. Based on our recent findings of their effects on erythroid differentiation, the following analyses are proposed to provide insight into their roles in human erythropoiesis. 1. To further characterize the effects of FRP and inhibin on erthroid progenitors: their dose response, dependency upon erythropoietin and specificity. The possible dependency of the observed effects on accessory cells will be examined by using cell depletion and reconstitution experiments, and by using enriched marrow progenitors at low cell density. Furthermore, the possible dependency on serum will also be analyzed byu-sing serum-free bone marrow culture. 2. To determine the lineage specificity for the effects of FRP and inhibin by exploring their effects on progenitor cells of other hematopoietic lineages and also their possible synergistic or antagonistic interactions with various recombinant factors. 3. To identify the types of cells which express FRP and/or inhibin with S1 nuclease analysis and in situ RNA hybridization. The functional entities of FRP/inhibin produced will be examined with bioassay and radioimmunoassay. 4. To investigate the mechanism of action for the observed effects of FRP and inhibin by examining their effects on proliferation of erythroid progenitor cells of bone marrow and their binding with putative surface receptors in K562 cells.