Dexamethasone administration to newborn mice alters mucosal and muscular morphology in the ileum and modulates IGF-I localization.
Glucocorticoid exposure accelerates the maturation of small bowel mucosa. We hypothesized that IGF-I, a mitogen and differentiating peptide expressed in small bowel, mediates steroid-induced change within the developing ileum. To investigate this possibility, we intraperitoneally administered 1 microg/gm/d of dexamethasone (DEX) or equal volumes of saline to litter-mate newborn mice. The animals were killed on d 1-3 of life and their ilea were harvested and prepared for microscopy. Tissue sections of ileum were examined for morphologic analyses, mucin staining, immunolocalization of IGF-I and -II, proliferating cell nuclear antigen (PCNA), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and in situ hybridization for IGF-I transcripts. Morphologic comparisons showed increases in goblet cell number, total cell number, and TUNEL-positive cells within the mucosa of DEX-treated animals. In contrast, the number of smooth muscle nuclei per cross-section was unchanged with DEX treatment despite a reduction in the number of PCNA-positive nuclei and an increased bowel circumference. These findings suggest the muscularis stretches to accommodate increasing bowel diameter. IGF-I peptide was localized to the mesenchyme of all control animals. After 48 h of DEX treatment, IGF-I was detected in the epithelia whereas mesenchymal IGF-I localization appeared diminished. In situ hybridization analyses for IGF-I transcripts showed no differences in localization between the groups. We conclude that DEX administration differentially affects adjacent tissues in the newborn ileum and that the associated changes in IGF-I localization are consistent with its participation in this process.
Gordon
P V
PV
Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of North Carolina at Chapel Hill, 27599-7596, USA.
Price
W A
WA
Stiles
A D
AD
D000818:Animals; D000831:Animals, Newborn; D003907:Dexamethasone / Q000008:administration & dosage* / Q000494:pharmacology; D007082:Ileum / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics
D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone