Insulin-like growth factors (IGFs) stimulate and dexamethasone inhibits IGF binding protein (BP)-5 expression in a mouse pituitary cell line

P. J. Fielder, J. P. Tauber, K. F. Wilson, H. M. Pham, R. G. Rosenfeld

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The mouse pituitary cell line AtT-20 was found to secrete two low MW IGFBPs into conditioned medium (CM). The major IGFBP migrated at approximately 29 kDa and a minor IGFBP of 24 kDa was also present on western ligand blots (WLB). Both IGFBPs were purified from CM by IGF-affinity chromatography followed by reverse phase-FPLC. N-terminal analysis revealed that the first 10 amino acids of the 29 kDa and the 24 kDa IGFBPs were homologous to corresponding sequences of both human and rat IGFBP-5 and IGFBP4, respectively. The 24 kDa IGFBP also crossreacted with a new antiserum specific for rodent IGFBP-4. The concentrations of both IGFBPs were increased by the addition of IGF-I, IGF-II, or insulin to the cell cultures, with IGFBP-5 demonstrating the greatest hormonal stimulation. The effects of IGF-I on IGFBP-5 expression were both time and dose dependent, with IGF-I being more potent than IGF-II, and IGF-II more potent than insulin. The relative potencies of these hormones in stimulating IGFBP-5 production were consistent with the peptides acting through the type-I IGF receptor. Similarly, the IGF-II analog [Leu 27]-IGF-II, which has very low affinity for the type-I receptor, only slightly stimulated an increase in IGFBP-5. Addition of dexamethasone to the cultures decreased both basal and IGF-stimulated IGFBP-5 production. Northern blotting demonstrated that IGF-I increased the expression of the mRNA for IGFBP-5, whereas dexamethasone decreased it. Together, these data suggest that the IGFs can increase IGFBP-5 production at both the protein and mRNA level.

Original languageEnglish (US)
Pages (from-to)226-234
Number of pages9
JournalGrowth regulation
Volume3
Issue number4
StatePublished - 1993

Keywords

  • AtT-20 cells
  • Dexamethasone
  • IGF-I
  • IGF-II
  • IGFBP-4
  • IGFBP-5

ASJC Scopus subject areas

  • Neuroscience(all)

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