PROGRAM PROJECT IN THE PATHOPHYSIOLOGY OF HUMAN GROWTH

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The long-term objective of this program project is to characterize mechanisms by which children both grow appropriately and fail to achieve normal stature. Following classification by conventional clinical characteristics, growth hormone and IGF I secretory criteia: (1) potential mutations in hGH and IGF I genes will be sought, polymorphism within and around these genes examined, and the regulation of these genes studied. (2) Structural abnormalities in circulating hGH and IGF peptides will be characterized and their receptor affinities and biologic activities quantified. (3) Structural defects of the hGH receptor will be delineated and the oligosaccharide unit structure, biosynthesis, and turnover of IGF receptors determined. (4) Possible aberrant post-receptor events will be defined, and (5) The in vivo significance and clinical consequences of these disturbances will be investigated with multi-faceted stable-isotope kinetic probes of protein anabolic and catabolic responses to exogenous growth hormone administration.