A GROWTH HORMONE SECRETAGOGUE RECEPTOR BASED PROTEIN, NUCLEIC ACIDS AND METHODS AND USES THEREOF

摘要

Ghrelin is a peptide hormone that binds its receptor, growth hormone secretatgogue receptor 1a (GHS-R1 a, ghrelin receptor), to promote adiposity and obesity in mammals. Ghrelin and its receptor are targets for therapeutic intervention to treat obesity-related disease and cancer. A soluble decoy GHS-R1 a receptor is developed that binds ghrelin in the periphery, preventing ghrelin from binding GHS-R1 on cells, thereby antagonizing ghrelin to treat obesity-related pathological conditions and cancer. GHS-R1 a is a transmembrane protein comprising an N-terminal extracellular domain (Nt), seven transmembrane regions and three extracellular loops (EC1, EC2 and EC3). The Nt, EC1 and EC2 are linked together, in the absence of the transmembrane regions, and fused to a Fc from an immunoglobulin, to create the decoy GHS-R1 a fusion protein, GHSR-Fc. The GHSR-Fc inhibits adiposity and weight gain in mice on a high fat diet (HFD), while the Nt and ECs on their own have no significant effect.