Milk-borne epidermal growth factor modulates intestinal transforming growth factor-alpha levels in neonatal rats.
Epidermal growth factor (EGF) is present in milk from various mammalian species, but its physiologic function in neonatal development remains unclear. Transforming growth factor-alpha (TGF-alpha) is a peptide structurally related to EGF, and its presence is detected in the developing small intestine of rats. The purpose of the present study was to examine the effect of milk-borne EGF on endogenous production of EGF and TGF-alpha in the small intestine of suckling rats. Neonatal rats were fed via gastrostomy either growth factor-free rat milk substitute (RMS) or RMS supplemented with EGF (100 ng/mL of RMS) from 8 to 12 d of age. Artificially reared rats were then compared with their dam-fed littermates. Animals fed the EGF-deficient diet RMS had markedly increased EGF and TGF-alpha mRNA levels in duodenum and ileum compared with dam-fed controls and significantly elevated total intestinal content of TGF-alpha peptide. Intestinal EGF content and EGF serum levels were significantly decreased in the RMS group compared with controls. The addition of EGF to the RMS diet normalized TGF-alpha mRNA levels in the duodenum and ileum, EGF mRNA levels in the ileum, and total intestinal TGF-alpha content and EGF serum levels to the levels measured in dam-fed littermates. Motility studies showed that enteral administration of EGF did not affect stomach emptying and intestinal transit. These studies indicate that exogenous milk-borne EGF modulates endogenous production of TGF-alpha in developing small intestine. It is likely that neither TGF-alpha nor EGF are solely responsible for small intestinal overgrowth of artificially reared neonatal rats.
Dvorak
B
B
Department of Pediatrics and Steele Memorial Children's Research Center, University of Arizona, Tucson 85724-5073, USA.
Williams
C S
CS
McWilliam
D L
DL
Shinohara
H
H
Dominguez
J A
JA
McCuskey
R S
RS
Philipps
A F
AF
Koldovsky
O
O
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001835:Body Weight; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005260:Female; D005769:Gastrointestinal Motility; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D008892:Milk; D051381:Rats; D017207:Rats, Sprague-Dawley; D016211:Transforming Growth Factor alpha / Q000378:metabolism*
D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor