Abstract

The overall objective of this project is to determine the physiologic role of somatomedin-C (Sm-C) and other circulating forms of somatomedin in the regulation of growth. Specifically, we will clone and sequence the gene for the somatomedin-C precursor in order to study the mechanisms involved in the biosynthesis of somatomedin-C and the subsequent processing of the gene product. These studies will be carried out in human tumor cell lines which we have identified as producers of somatomedin-C-like activity. We will use the monoclonal antibodies which we have obtained against somatomedin-C production or storage. We will passively immunize young animals with these antibodies to determine the role of somatomedin-C in growth. The contributions of somatomedin-C to the mitogenic activity of serum will also be identified by immunoneutralization. We will continue to fractionate large quantities of human plasma to produce somatomedin-C, IFG-II, and related substances. We will determine the role of somatomedin-C in the feedback mechanisms controlling the secretion of growth hormone and other pituitary hormones and the mechanisms by which somatomedin-C interacts with other peptide growth factors in regulating cell replication.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM001022-30
Application #
3150673
Study Section
Endocrinology Study Section (END)
Project Start
1976-09-01
Project End
1987-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
30
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Hernandez, E R; Resnick, C E; Svoboda, M E et al. (1988) Somatomedin-C/insulin-like growth factor I as an enhancer of androgen biosynthesis by cultured rat ovarian cells. Endocrinology 122:1603-12
Hynes, M A; Van Wyk, J J; Brooks, P J et al. (1987) Growth hormone dependence of somatomedin-C/insulin-like growth factor-I and insulin-like growth factor-II messenger ribonucleic acids. Mol Endocrinol 1:233-42
Casella, S J; Smith, E P; van Wyk, J J et al. (1987) Isolation of rat testis cDNAs encoding an insulin-like growth factor I precursor. DNA 6:325-30
Adashi, E Y; Resnick, C E; Svoboda, M E et al. (1986) Synergistic interactions of somatomedin-C with adenosine 3',5'-cyclic monophosphate-dependent granulosa cell agonists. Biol Reprod 34:81-8
Adashi, E Y; Resnick, C E; Svoboda, M E et al. (1986) Follicle-stimulating hormone enhances somatomedin C binding to cultured rat granulosa cells. Evidence for cAMP dependence. J Biol Chem 261:3923-6
Van Wyk, J J (1986) Peptide growth factors: a new frontier for pediatric endocrinology. Acta Endocrinol Suppl (Copenh) 279:71-81
Lund, P K; Moats-Staats, B M; Hynes, M A et al. (1986) Somatomedin-C/insulin-like growth factor-I and insulin-like growth factor-II mRNAs in rat fetal and adult tissues. J Biol Chem 261:14539-44
Casella, S J; Han, V K; D'Ercole, A J et al. (1986) Insulin-like growth factor II binding to the type I somatomedin receptor. Evidence for two high affinity binding sites. J Biol Chem 261:9268-73
Adashi, E Y; Resnick, C E; Svoboda, M E et al. (1986) Somatomedin-C as an amplifier of follicle-stimulating hormone action: enhanced accumulation of adenosine 3',5'-monophosphate. Endocrinology 118:149-55
Adashi, E Y; Resnick, C E; Svoboda, M E et al. (1985) Somatomedin-C synergizes with follicle-stimulating hormone in the acquisition of progestin biosynthetic capacity by cultured rat granulosa cells. Endocrinology 116:2135-42

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