Amyloid Formation by Human Growth Hormone

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The tendency of proteins to form amyloid is proposed to be inherent that can either perform native functions in a host such as providing mechanical strength (e.g.: spider silk), storage (e.g.: hormone storage), or can result in fatal effects like the plaques formed in amylodosis in human. Recently it was reported that, hormones are stored in secretory granules as amyloid- like fibrils (Maji et al., 2009). But the conditions necessary for amyloid formation varies for different hormones. Here, growth hormone (GH) is taken to study the amyloid formation and its role in hormone storage within the secretory granule of anterior pituitary. Analysis of GH protein sequence using TANGO and WALTZ algorithms showed that it has amyloidogenic potential. Further the conditions for GH aggregation were studied in presence and absence of various solvents, denaturants, glycosaminoglycans, salts and cations. It was found that GH in presence of equimolar concentration of Zn2+ ions formed amyloid like aggregates as observed by secondary structural changes by CD and ability to bind amyloid specific dyes such as congo red and thioflavin T. These aggregates showed fibril-like morphology observed under TEM. The role of Zn2+ ions in GH aggregation was further probed by NMR analysis.The involvement of Zn2+ in amyloid formation is confirmed as incubation of GH in presence of Zn2+ ions and EDTA didn’t result in any amyloid formation. Additionally GH fibrils formed with Zn2+ ions destabilizes when incubated with EDTA and results in release of monomers. This data suggests possible mechanism of GH storage and release in somatotrophs of anterior pituitary which could further help in understanding GH deficiency caused due to faults in storage of GH in secretory granules.