Growth hormone rapidly activates insulin-like growth factor I gene transcription in vivo

David P. Bichell, Kiyoshi Kikuchi, Peter Rotwein

Research output: Contribution to journalArticle

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Abstract

Many of the growth-promoting properties of GH are mediated by insulin-like growth factor I (IGF-I), a highly conserved circulating 70-amino acid peptide. Recent studies have shown that multiple mechanisms influence IGF-I gene expression, including transcription from two promoters, alternative RNA splicing, and variable polyadenylation. In order to determine how GH regulates IGF-I gene expression we have analyzed the response of hypophysectomized rats to a single ip injection of recombinant GH. A rise in hepatic IGF-I mRNA was detected within 2 h of GH treatment, with peak values of more than 15-fold above untreated animals by 4 h, and a decline by 16 h. A coordinate increase was seen in all IGF-I mRNA splicing and polyadenylation variants, indicating that neither alternative RNA processing nor differential poly A addition were altered by GH. Transcription run-on experiments using isolated hepatic nuclei and direct analysis of nuclear RNA demonstrated a rise in nascent IGF-I mRNA within 30 min of GH treatment, with peak levels reaching more than 10-fold above background by 2 h and declining by 6 h. As determined by RNase protection assays, transcripts directed by each promoter were coordinately and equivalently activated after GH. A single GH-responsive DNase I hypersensitive site was mapped in chromatin to the second IGF-I intron. This site exhibited rapid kinetics of induction which mirrored the pattern of transcriptional stimulation after GH treatment. These experiments show that GH enhances IGF-I expression in vivo by predominantly transcriptional mechanisms. The rapid kinetics of IGF-I gene activation and the temporally associated chromatin changes demonstrate a direct link between a GH-dependent signal transduction pathway and nuclear events.

Original languageEnglish (US)
Pages (from-to)1899-1908
Number of pages10
JournalMolecular Endocrinology
Volume6
Issue number11
StatePublished - 1992
Externally publishedYes

Fingerprint

Insulin-Like Growth Factor I
Growth Hormone
Genes
Polyadenylation
Messenger RNA
Chromatin
Gene Expression
Nuclear RNA
Poly A
Liver
Deoxyribonuclease I
Alternative Splicing
Ribonucleases
Introns
Transcriptional Activation
Signal Transduction
Therapeutics
RNA
Amino Acids
Peptides

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Growth hormone rapidly activates insulin-like growth factor I gene transcription in vivo. / Bichell, David P.; Kikuchi, Kiyoshi; Rotwein, Peter.

In: Molecular Endocrinology, Vol. 6, No. 11, 1992, p. 1899-1908.

Research output: Contribution to journalArticle

Bichell, DP, Kikuchi, K & Rotwein, P 1992, 'Growth hormone rapidly activates insulin-like growth factor I gene transcription in vivo', Molecular Endocrinology, vol. 6, no. 11, pp. 1899-1908.
Bichell, David P. ; Kikuchi, Kiyoshi ; Rotwein, Peter. / Growth hormone rapidly activates insulin-like growth factor I gene transcription in vivo. In: Molecular Endocrinology. 1992 ; Vol. 6, No. 11. pp. 1899-1908.
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