Differential regulation of insulin-like growth factor binding protein secretion from human decidual cells by IGF-I, insulin, and relaxin

K. M. Thrailkill, D. R. Clemmons, W. H. Busby, S. Handwerger

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Several growth hormone-independent 25-31,000 kD insulin-like growth factor binding proteins (IGF-BPs) have been identified in plasma, extravascular fluids, and various cell-conditioned media. Cultured human decidual cells release three IGF-BPs with 24,000, 30,000, and 34,000 M(r). Using ligand blot analysis and an RIA for the 30,000-M(r) form (IGF-BP-1), we examined the effects of IGF-I (10-1,000 ng/ml), insulin (10-10,000 ng/ml), and relaxin (10-250 ng/ml) on decidual cell IGF-BP release after 120 h of hormone exposure. IGF-I inhibited release of both IGF-BP-1 and the 24,000 M(r) form. Inhibition of IGF-BP-1 release was noted after 48 h of treatment and was progressive throughout the subsequent 120 h. Insulin stimulated a fourfold increase in release of the 24,000-M(r) protein while inhibiting IGF-BP-1 release comparable to IGF-I. α-IR3, a monoclonal antibody to the IGF-I receptor, blocked ~33% of the IGF-I response but had no effect on insulin-mediated IGF-BP-1 inhibition. Relaxin stimulated a 2.4-fold increase in release of the 24,000-M(r) form and a 16-fold increase in the 30,000-M(r) protein after 120 h. Stimulation of the 30,000-M(r) protein was inhibited by the addition of cycloheximide (50 μg/ml). Both IGF-I and insulin also blocked the relaxin-mediated increase in IGF-BP-1. These studies suggest that three structurally related proteins differentially regulate IGF-BP secretion possibly via activation of distinct receptor subtypes.

Original languageEnglish
Pages (from-to)878-883
Number of pages6
JournalJournal of Clinical Investigation
Volume86
Issue number3
DOIs
StatePublished - 1990

Keywords

  • IGF-BPs
  • decidua
  • insulin-like growth factors
  • relaxin

ASJC Scopus subject areas

  • Medicine (all)

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