Human hepatoma cells synthesize and secrete insulin-like growth factor Ia prohormone under growth hormone control

C. A. Conover, B. K. Baker, L. K. Bale, J. T. Clarkson, F. Liu, R. L. Hintz

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Nucleotide sequencing of cDNAs encoding human insulin-like growth factor I (IGF-I) predicts the existence of two different prohormone forms of IGF-I. The E peptide regions extend the carboxy-terminus of the 70 amino acid core IGF-I molecule (BCAD domains) by either an additional 35 (IGF-Ia) or 77 (IGF-Ib) amino acids. Employing antiserum directed against a peptide sequence unique to the E peptide region of IGF-Ia prohormone, we have identified EIa immunoreactive material (IR-EIa) in the conditioned medium of a human hepatoma cell line, HepG2. Human growth hormone (GH) had dose-dependent stimulatory effects on IR-EIa secretion; incubation of HepG2 cells with GH at maximal concentrations (1-5 μg/ml) increased specific IR-EIa in 24 h conditioned medium 3-fold. The addition of human placental lactogen, insulin, IGF-I, dexamethasone, β-estradiol, or progesterone had no significant effect. Acid chromatography of HepG2 cell conditioned medium revealed a single elution peak of IR-EIa corresponding to Mr = 12,000-20,000. There was no immunologically detectable 7500 Mr IGF-I peptide in acid-chromatographed conditioned medium under either basal or stimulated conditions. Biosynthetic labelling of HepG2 cell products with [35S]Trans label and immunoprecipitation with antisera specific to the E or to the AD regions of the IGF-Ia molecule indicated a single species of approx. 14,000 Mr. These data indicate that the E peptide region of IGF-Ia is translated and released as part of the larger molecule in cultured HepG2 cells, and that the levels of this prohormone are regulated by GH.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalRegulatory Peptides
Volume48
Issue number1-2
DOIs
StatePublished - Oct 20 1993

Keywords

  • Growth hormone
  • HepG2
  • IGF-Ia

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Clinical Biochemistry
  • Cellular and Molecular Neuroscience

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