Stimulatory actions of insulin-like growth factor-I and transforming growth factor-α on intestinal neurotensin and peptide YY

Heung Man Lee, Vidyavathi Udupi, Ella W. Englander, Srinivasan Rajaraman, Robert J. Coffey, George H. Greeley

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Proliferation of the gastrointestinal mucosa is stimulated by the growth factors, insulin-like growth factor-I (IGF-I) and transforming growth facter-α (TGF-α), or the closely related epidermal growth factor (EGF), as well as the gastrointestinal hormones, gastrin, neurotensin (NT), and peptide YY (PYY). The stimulatory actions of these growth factors or gastrointestinal hormones on the gastrointestinal mucosa may be direct or mediated in part by gastrointestinal peptides or the growth factors, respectively. The purpose of these studies therefore was to examine the effects of IGF-I and TGF-α on stomach gastrin and intestinal NT and PYY gene expression [i.e. messenger RNA (mRNA), peptide levels] and secretion. Mice were given recombinant human IGF-I (3, 6 mg/kg BW/day x 14 days). Transgenic mice with the rat TGF-α gene linked to a metallothionein promoter were used as a model of chronic TGF-α excess. IGF-I and TGF-α did not affect gastrin gene expression. Steady-state intestinal NT and PYY mRNA and peptide levels were elevated in a dose-related manner by IGF. TGF-α also increased intestinal expression of NT and PYY peptide, but not mRNA levels. Basal serum levels of PYY were elevated by IGF-I and TGF-α. IGF-I and TGF-α did not increase intestinal chromogranin A (CGA) gene expression, a marker of endocrine cells, or the density of PYY-containing cells in the colon, indicating that the elevations in intestinal gut peptide gene expression by IGF-I and TGF-α are not due simply to an increased number of enteroendocrine cells. IV infusion of EGF also stimulated release of PYY in the dog. Together, these findings indicate that IGF-I and TGF-α may cause secretion of gut hormones and exert a major upregulatory influence on the regulation of intestinal peptide hormone homeostasis.

Original languageEnglish (US)
Pages (from-to)4065-4069
Number of pages5
JournalEndocrinology
Volume140
Issue number9
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Endocrinology

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