Insulin-like growth factor (IGF) suppression of IGFBP-1 production: evidence for mediation by the type I IGF receptor

Phillip Lee, Adisak Suwanichkul, Laura A. DePaolis, Mark B. Snuggs, Sheila L. Morris, David R. Powell

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The regulation of insulin-like growth factor binding protein-1 (IGFBP-1) by its ligands, IGF-I and IGF-II, was studied in continuous cultures of HepG2 human hepatoma cells. Both IGF-I and IGF-II in concentrations as low as 1-10 nmol/l caused significant suppression of IGFBP-1 protein levels. This suppression was accompanied by decreased IGFBP-1 mRNA levels occurring within 2-4 h of exposure to IGF-I or IGF-II, and by a significant decrease in IGFBP-1 promoter activity. IGF-I and IGF-II were equipotent in suppressing basal levels of IGFBP-1 protein, mRNA and promoter activity. IGF-I, IGF-II, and IGF-analogs with low IGFBP-1 affinity, (des 1-3)IGF-I and long R3IGF-I, all potently suppressed the previously characterized increase in IGFBP-1 protein levels and promoter activity induced by cAMP and theophylline. In contrast, [Leu-27]IGF-II, which interacts with the type II but not type I IGF receptor, had no effect on IGFBP-1 protein levels or promoter activity. Our data indicate that IGFBP-1 production is inhibited by its ligands, IGF-I and IGF-II, and that this effect is probably mediated at the transcriptional level. The effects of IGF-I and IGF-II apparently occur as a result of binding to the type I IGF receptor, and are similar to the previously characterized suppressive effects of insulin on IGFBP-1 transcription mediated through the insulin receptor. When considered with previous data regarding expression of IGFBP-1 and the type I IGF receptor, our results suggest that IGF regulation of IGFBP-1 may play an as yet undefined role in fetal development and postnatal hepatic regeneration.

Original languageEnglish (US)
Pages (from-to)199-206
Number of pages8
JournalRegulatory Peptides
Volume48
Issue number1-2
DOIs
StatePublished - Oct 20 1993
Externally publishedYes

Fingerprint

Insulin-Like Growth Factor Binding Protein 1
IGF Type 1 Receptor
Somatomedins
Insulin-Like Growth Factor II
Insulin-Like Growth Factor I
Proteins
Ligands
Messenger RNA
Insulin Receptor
Transcription
Theophylline
Fetal Development
Regeneration
Hepatocellular Carcinoma

Keywords

  • IGF
  • Suppression
  • Type I receptor

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Neuroscience(all)

Cite this

Insulin-like growth factor (IGF) suppression of IGFBP-1 production : evidence for mediation by the type I IGF receptor. / Lee, Phillip; Suwanichkul, Adisak; DePaolis, Laura A.; Snuggs, Mark B.; Morris, Sheila L.; Powell, David R.

In: Regulatory Peptides, Vol. 48, No. 1-2, 20.10.1993, p. 199-206.

Research output: Contribution to journalArticle

Lee, Phillip ; Suwanichkul, Adisak ; DePaolis, Laura A. ; Snuggs, Mark B. ; Morris, Sheila L. ; Powell, David R. / Insulin-like growth factor (IGF) suppression of IGFBP-1 production : evidence for mediation by the type I IGF receptor. In: Regulatory Peptides. 1993 ; Vol. 48, No. 1-2. pp. 199-206.
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