Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD020805-04
Application #
3096943
Study Section
Maternal and Child Health Research Committee (HDMC)
Project Start
1986-01-01
Project End
1990-11-30
Budget Start
1989-01-01
Budget End
1990-11-30
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130

  Publications

Umayahara, Y; Billiard, J; Ji, C et al. (1999) CCAAT/enhancer-binding protein delta is a critical regulator of insulin-like growth factor-I gene transcription in osteoblasts. J Biol Chem 274:10609-17
Umayahara, Y; Ji, C; Centrella, M et al. (1997) CCAAT/enhancer-binding protein delta activates insulin-like growth factor-I gene transcription in osteoblasts. Identification of a novel cyclic AMP signaling pathway in bone. J Biol Chem 272:31793-800
Mittanck, D W; Kim, S W; Rotwein, P (1997) Essential promoter elements are located within the 5' untranslated region of human insulin-like growth factor-I exon I. Mol Cell Endocrinol 126:153-63
Pike, L J; Casey, L (1996) Localization and turnover of phosphatidylinositol 4,5-bisphosphate in caveolin-enriched membrane domains. J Biol Chem 271:26453-6
Rotwein, P; Bichell, D P; Kikuchi, K (1993) Multifactorial regulation of IGF-I gene expression. Mol Reprod Dev 35:358-63;discussion 363-4
Bichell, D P; Rotwein, P; McCarthy, T L (1993) Prostaglandin E2 rapidly stimulates insulin-like growth factor-I gene expression in primary rat osteoblast cultures: evidence for transcriptional control. Endocrinology 133:1020-8
Daughaday, W H; Trivedi, B (1992) Heterogeneity of serum peptides with immunoactivity detected by a radioimmunoassay for proinsulin-like growth factor-II E domain: description of a free E domain peptide in serum. J Clin Endocrinol Metab 75:641-5
Daughaday, W H; Trivedi, B (1992) Measurement of derivatives of proinsulin-like growth factor-II in serum by a radioimmunoassay directed against the E-domain in normal subjects and patients with nonislet cell tumor hypoglycemia. J Clin Endocrinol Metab 75:110-5
Kim, S W; Lajara, R; Rotwein, P (1991) Structure and function of a human insulin-like growth factor-I gene promoter. Mol Endocrinol 5:1964-72
Daughaday, W H; Trivedi, B (1991) Clinical aspects of GH binding proteins. Acta Endocrinol (Copenh) 124 Suppl 2:27-32

Showing the most recent 10 out of 12 publications