PROGRAM PROJECT IN THE PATHOPHYSIOLOGY OF HUMAN GROWTH

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.