Insulin-like growth factor-I governs submucosal growth and thickness in the newborn mouse ileum.
Spontaneous intestinal perforations in extremely premature infants are associated with glucocorticoid-induced thinning of the ileal bowel wall. We have previously demonstrated that insulin-like growth factor-1 (IGF-1) is abundant within the submucosa of the newborn mouse ileum but is diminished by glucocorticoid exposure, concomitant with bowel wall thinning. These findings prompted us to hypothesize that IGF-I governs submucosal growth during neonatal gut development and that diminished IGF-I abundance results in submucosal thinning. Heterozygous IGF-I knockout, wild type and homozygous IGF-I over-expresser newborn mice were euthanized at 3 d of life. Additionally, wild type newborn mice received daily dexamethasone (DEX) (1microg/gm/d) or vehicle control on days of life 1 and 2 and were also euthanized at 3 d of life. Their ileums were harvested, fixed and the resulting sections were processed in parallel for IGF-I immunohistochemistry and morphometric measurements of submucosal thickness and bowel diameter. Immunolocalization of IGF-I in each genotype was also compared with that seen in DEX-treated and control mice euthanized at the same time of life. IGF-I heterozygous knockouts had diminished submucosal IGF-I immunolocalization (similar to that seen in DEX-treated newborn mice) whereas homozygous IGF-I over-expressers exceeded that seen within wild type mice. IGF-I genotype and submucosal abundance was positively correlated with ileal submucosal thickness. DEX treatment of newborn mice diminished IGF-I and caused significant thinning of the submucosa compared with controls. Submucosal growth and thickness in the neonatal mouse ileum is governed by IGF-I and is diminished by dexamethasone treatment.
Herman
Andrew C
AC
Division of Neonatology Department of Pediatrics, PO Box 800386, University of Virginia Health System, Charlottesville, VA 22908, USA.
Carlisle
Erica M
EM
Paxton
Jessica B
JB
Gordon
Phillip V
PV
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D017931:DNA Primers; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000502:physiology*; D007413:Intestinal Mucosa / Q000254:growth & development; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010375:Pedigree
D017931:DNA Primers; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone