Abstract
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 μg/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 ileums 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.
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Abbreviations
- DEX:
-
dexamethasone
- PCNA:
-
proliferating cell nuclear antigen
- TUNEL:
-
terminal deoxynucleotide transferase-mediated dUTP nick end labeling
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Acknowledgements
The authors thank Brian Brighton and Ward Jarvis for their technical assistance, Dr. Kay Lund and Dr. Joe Rutledge for their helpful discussions, and Dr. Billie Moats-Staats for her helpful discussions, reading of the manuscript and suggestions.
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Gordon, P., Price, W. & Stiles, A. Dexamethasone Administration to Newborn Mice Alters Mucosal and Muscular Morphology in the Ileum and Modulates IGF-I Localization. Pediatr Res 49, 93–100 (2001). https://doi.org/10.1203/00006450-200101000-00020
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DOI: https://doi.org/10.1203/00006450-200101000-00020
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