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.
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