Dexamethasone changes the composition of insulin-like growth factor binding proteins in the newborn mouse ileum.
BACKGROUND
Early postnatal glucocorticoid exposure accelerates the maturation of the bowel mucosa but results in bowel wall thinning in the newborn mouse ileum and increases the risk of focal ileal perforation in extremely premature infants. We have previously demonstrated a redistribution of insulin-like growth factor-I (IGF-I) from the submucosa in control animals to the distal villi of those treated with early postnatal dexamethasone, implicating IGF-I as an important mediator of dexamethasone's capacity to alter tissue growth. To investigate the possibility that IGF binding proteins (IGFBPs) might contribute to this process, we characterized the localization and abundance of IGFBP peptides and mRNAs in the same model.


METHODS
Newborn mice received daily intraperitoneal injections of dexamethasone (l microg/g) or phosphate-buffered saline and then were euthanized on day 3 of life. Their ileums were harvested and prepared for microscopy. Tissue sections of ileum from both treatment conditions were processed in parallel for immunolocalization of each of the six IGFBP peptides and for in situ hybridization of each of the six IGFBP transcripts.


RESULTS
Transcripts for IGFBP-1, -2, and -3 were highly abundant and ubiquitous the ileal mucosa, whereas transcripts for IGFBP-4, -5, and -6 were less abundant in epithelial cells. There were no differences in abundance between control and dexamethasone-treated ileum with regard to mRNA localization or abundance for IGFBP-1, -2, -3, and -6. In contrast, mRNA transcripts for IGFBP-4 and -5 were modestly increased with dexamethasone treatment (although only IGFBP-4 was significant). Strikingly different patterns of IGFBP immunolocalization were observed between control and dexamethasone-treated animals. IGFBP-1, -2, -3, and -5 were not detected in control ileum, whereas IGFBP-4 and -6 were both present in the mucosa. In contrast, dexamethasone treatment resulted in dramatic mucosal increases in IGFBP-2, -3, -4, and -5, paralleling the changing distribution of IGF-I that we previously reported.


CONCLUSIONS
Taken together, these findings further implicate the IGF system as an important participant in dexamethasone-induced maturation in the newborn mouse ileum.
Gordon
Phillip V
PV
Division of Neonatology, Department of Pediatrics, University of Virginia Health Sciences, Charlottesville 22908, USA. pvg4n@virginia.edu
Moats-Staats
Billie M
BM
Stiles
Alan D
AD
Price
Wayne A
WA
D000818:Animals; D000831:Animals, Newborn; D003907:Dexamethasone / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D003907:Dexamethasone