Milk-Borne Epidermal Growth Factor Modulates Intestinal Transforming Growth Factor-α Levels in Neonatal Rats

Abstract

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.

Differential expression of EGF receptor in the pig duodenum during the transition phase from maternal milk to solid food

“…The presence of biologically active peptides, including EGF, in the milk of a number of mammals is well established, 1,9,10,23 but little is known about changes in cellular distribution of the EGF-R during the early weaning period of pigs when the transition from maternal milk to solid food occurs. The main purpose of the present study was to investigate differences in the expression of EGF-R and its effects possibly caused by food transition.…”

“…[5][6][7][8] This molecule has also been found in the milk, urine, and plasma of several species (e.g., humans and pigs) in various concentrations. 1,9,10 The receptor for EGF binding (EGF-R) belongs to the classical receptor tyrosine kinase family, the members of which are involved in a large range of physiological effects, such as proliferation, differentiation, and cell survival. 11,12 Furthermore, it is involved in the turnover of proteins of the extracellular matrix and plays a role in the malignant transformation of some cells.…”

“…Several growth-stimulating factors, such as insulin-like growth factor (IGF), transforming growth factor-α (TGFα), and epidermal growth factor (EGF) are thought to play an important role in the development of the intestine of newborn animals. [1][2][3][4] Epidermal growth factor, a short polypeptide of 53 amino acids, is produced in various tissues such as brain and the urogenital and gastrointestinal tracts. [5][6][7][8] This molecule has also been found in the milk, urine, and plasma of several species (e.g., humans and pigs) in various concentrations.…”

Early Postnatal Dexamethasone Diminishes Transforming Growth Factor α Localization within the Ileal Muscularis Propria of Newborn Mice and Extremely Low-birth-weight Infants

“…In addition, EGF is also secreted into the duodenal lumen by Brunner's glands. Messenger RNA (mRNA) for both EGF and transforming growth factor ␣ (TGF-␣) is expressed in the intestines of growing animals [15]. In rat pups, the abundance of EGF mRNA is much greater in the proximal bowel than in the ileum.…”

Evaluation of the Growth Promoting Potency of 6 Different Synthetic Peptides Using Rama-27 Cell-Line

“…insulin-like growth factor (IGF) and epidermal growth factor (EGF) are present in the mammalian milk i.e. human, mouse, rat and swine [12,[20][21][22] . Their physiological mechanism of action typically depends upon acting as signalling molecules between cells e.g.…”