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United States Department of Agriculture-Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030
Our objective was to determine how dexamethasone
(Dex) affects gastrointestinal protein metabolism and growth in
neonatal pigs. Two-day-old pigs were given daily subcutaneous
injections of either Dex (1 mg/kg body wt,
n = 7) or saline (control,
n = 6) for 7 days. In vivo protein
synthesis was measured after 7 days with a bolus of
[3H]phenylalanine.
Tissue protein contents were measured in an initial control group of
2-day-old pigs and in control and Dex pigs after 7 days to estimate
protein accretion and degradation. In control pigs, the protein
accretion in the ileum was nearly sixfold greater than in the jejunum
during the 7-day period. Dex nominally altered stomach growth but
completely blocked the accretion of protein and DNA in the jejunum and
ileum, with reduced villus height in the ileum. Dex increased the
fractional protein degradation rate in the ileum (28%) and decreased
the absolute protein synthesis rate in the jejunum and ileum by 17 and
21%, respectively. Dex resulted in a 40% lower total intestinal
lactase activity compared with controls via reductions in both specific
activity and tissue mass, especially in the ileum. Dex significantly
decreased the circulating concentrations of insulin-like growth factor
(IGF) I and IGF-binding protein (IGFBP)-1, -2, and -3. However, the tissue abundance of the IGF-I receptor in the stomach and ileum was
greater in Dex pigs than controls. Our results suggest that Dex
significantly inhibits small intestinal growth via both increased degradation and decreased synthesis of protein. Furthermore, the inhibition of intestinal growth resulted in significantly decreased lactose digestive capacity.
protein synthesis; glucocorticoids; insulin-like growth factor I; insulin-like growth factor-binding proteins; lactase
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