Growth Factors (GFs), such as Epidermal Growth Factor (EGF) and insulin- like Growth Factors (IGFs)-I and -II are present in most mammalian milks in concentrations sufficient to have biological effects. The preceding Project #1 (PI: O. Koldovsky) dealt with the sources of the mentioned GFs for the neonate. The purpose of this project is to examine the hypothesis that milk-borne GFs influence both growth and differentiation of the gastrointestinal tract (GI) of the suckling, and also have effects at sites distal to the GI tract. Studies dealing specifically with the effect on the liver and its function are the subject of Project #3 (PI: R. McCuskey). To test the hypothesis that milk-borne GFs affect the growth and development of the gastrointestinal (GI) tract and beyond, we will feed suckling rats either RMS or RMS supplemented with EGF, IGF-I and IGF- II individually, and in combination, in doses corresponding to the intake of these GF-s in milk. We hypothesize that feeding of GF-supplemented RMS to suckling rats will produce dose dependent changes in the growth of specific organs, including the liver, brain, cardiac and striated muscle, stomach and small bowel, and that IGFs and/or EGF fed to sucklings will stimulate cellular differentiation both locally (GI tract) and distally (eye, ear, etc.) To test the hypothesis that milk-borne GFs significantly alter a number of specific GI tract functions when given to the suckling chronically, we will study changes in several specific GI functions; namely, gastric evacuation, intestinal propulsive motility, and intestinal transport in suckling rats fed with RMS or RMS supplemented with GFs. Furthermore, we will explore the mechanisms involved in the absorption of GFs by the neonatal GI tract. The specificity of the inhibitable process for GF absorption from the GI tract will be tested by determining effects of excess EGF, TGFa, and IGFs on GF peptide absorption using the jejunal and ileal loop models of in vivo absorption. Since rat milk is known to contain factors that inhibit degradation of several peptide hormones by rat gastric and intestinal juices in vitro, we will characterize further (using HPLC) the fractions of rat milk responsible for this protective property and analyze their role in the mechanism of GI absorption of GF in suckling rats. We will also test the hypothesis that an enterohepatic circulation of IGFs exists, contributing to the increase of effectiveness of milk-borne and endogenously produced IGFs. Lastly, we will test the hypothesis that a milk-borne source of epidermal growth factor and insulin-like growth factors functions in the regulation of whole body long-chain fatty acid oxidation capacity in the suckling rat.
| Sørensen, Karen Kristine; Simon-Santamaria, Jaione; McCuskey, Robert S et al. (2015) Liver Sinusoidal Endothelial Cells. Compr Physiol 5:1751-74 |
| Kling, Pamela J; Willeitner, Andrea; Dvorak, Bohuslav et al. (2008) Enteral erythropoietin and iron stimulate erythropoiesis in suckling rats. J Pediatr Gastroenterol Nutr 46:202-7 |
| McCuskey, Robert S (2008) The hepatic microvascular system in health and its response to toxicants. Anat Rec (Hoboken) 291:661-71 |
| Kling, Pamela J; Taing, K Muy; Dvorak, Bohuslav et al. (2006) Insulin-like growth factor-I stimulates erythropoiesis when administered enterally. Growth Factors 24:218-23 |
| Dvorak, Bohuslav; Halpern, Melissa D; Holubec, Hana et al. (2004) Rat milk decreases necrotizing enterocolitis in a rat model. Adv Exp Med Biol 554:471-3 |
| Dvorak, Bohuslav; Fituch, Camellia C; Williams, Catherine S et al. (2004) Concentrations of epidermal growth factor and transforming growth factor-alpha in preterm milk. Adv Exp Med Biol 554:407-9 |
| Kling, Pamela J; Hutter, John J (2003) Hematologic abnormalities in severe neonatal necrotizing enterocolitis: 25 years later. J Perinatol 23:523-30 |
| Dvorak, Bohuslav; Fituch, Camellia C; Williams, Catherine S et al. (2003) Increased epidermal growth factor levels in human milk of mothers with extremely premature infants. Pediatr Res 54:15-9 |
| Halpern, Melissa D; Dominguez, Jessica A; Dvorakova, Katerina et al. (2003) Ileal cytokine dysregulation in experimental necrotizing enterocolitis is reduced by epidermal growth factor. J Pediatr Gastroenterol Nutr 36:126-33 |
| Halpern, Melissa D; Holubec, Hana; Dominguez, Jessica A et al. (2003) Hepatic inflammatory mediators contribute to intestinal damage in necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol 284:G695-702 |
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