Abstract

The goal of this project is to understand the molecular basis of GH action, using the serine protease inhibitor (Spi) 2 locus in the rats as a model system for the study of the nuclear events following GH signal transduction. Previous studies have demonstrated that Spi 2.1 contains a GH-response element (GHRE), which shows GH-specific binding requiring phosphorylation for activity. The applicant now proposes: 1) To isolate GH-inducible nuclear factor (GHINF) by GHRE affinity chromatography. Peptide sequences of the purified protein will be used to generate oligonucleotides for isolation of a cDNA for GHINF; 2) To characterize GHINF, in terms of similarity to other transcription factors, tissue specificity and ontogeny; 3) To examine the role of GHINF and its phosphorylation in GH action.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK032817-09A3
Application #
2138876
Study Section
Endocrinology Study Section (END)
Project Start
1983-08-01
Project End
1997-11-30
Budget Start
1995-01-01
Budget End
1995-11-30
Support Year
9
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
University of Minnesota Twin Cities
Department
Pediatrics
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455

  Publications

Humbert, J T; Bergad, P L; Masha, O et al. (2000) Growth hormone action in hypothyroid infant rats. Pediatr Res 47:250-5
Bergad, P L; Towle, H C; Berry, S A (2000) Yin-yang 1 and glucocorticoid receptor participate in the Stat5-mediated growth hormone response of the serine protease inhibitor 2.1 gene. J Biol Chem 275:8114-20
Bergad, P L; Schwarzenberg, S J; Humbert, J T et al. (2000) Inhibition of growth hormone action in models of inflammation. Am J Physiol Cell Physiol 279:C1906-17
Berry, S A; Bergad, P L; Stolz, A M et al. (1999) Regulation of Spi 2.1 and 2.2 gene expression after turpentine inflammation: discordant responses to IL-6. Am J Physiol 276:C1374-82
Bergad, P L; Towle, H C; Berry, S A (1999) Definition of a high affinity growth hormone DNA response element. Mol Cell Endocrinol 150:151-9
Bergad, P L; Shih, H M; Towle, H C et al. (1995) Growth hormone induction of hepatic serine protease inhibitor 2.1 transcription is mediated by a Stat5-related factor binding synergistically to two gamma-activated sites. J Biol Chem 270:24903-10
Berry, S A; Bergad, P L; Whaley, C D et al. (1994) Binding of a growth hormone-inducible nuclear factor is mediated by tyrosine phosphorylation. Mol Endocrinol 8:1714-9
Berry, S A; Yoon, J B; List, J et al. (1993) Hepatic fatty acid-binding protein mRNA is regulated by growth hormone. J Am Coll Nutr 12:638-42
Berry, S A; Bergad, P L; Bundy, M V (1993) Expression of growth hormone-responsive serpin mRNAs in perinatal rat liver. Am J Physiol 264:E973-80
Schwarzenberg, S J; Yoon, J B; Seelig, S et al. (1992) Discoordinate hormonal and ontogenetic regulation of four rat serpin genes. Am J Physiol 262:C1144-8

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