title: Erythropoietin acts as a trophic factor in neonatal rat intestine.
abstract: BACKGROUND
  Erythropoietin (Epo) receptors are present on enterocytes of fetal and neonatal small bowel but the role of Epo in the bowel is not known.
  
  
  OBJECTIVE
  We tested the following hypotheses: (1) enterally dosed Epo is absorbed from the intestines of neonatal rats, (2) Epo acts as a trophic factor in developing small bowel, and (3) the trophic effects of Epo are dependent on the route of administration.
  
  
  METHODS
  The dose dependent effects of enterally dosed recombinant human erythropoietin (rEpo 0--1000 U/kg/day) were studied in artificially raised rat pups and compared with dam raised controls and dam raised pups given rEpo in rat milk. After one week, reticulocyte counts, haematocrits, and plasma Epo concentrations were measured, and calibrated morphometric measurements of villi were performed. The effects of route of rEpo administration (enteral v parenteral) on erythropoiesis, bowel growth, and disaccharidase activity were studied in nursing pups treated for one and two weeks.
  
  
  RESULTS
  Serum Epo concentrations ranged from undetectable (<0.6 mU/ml) to 8.4 mU/ml in control and enterally dosed pups (median 1.8 mU/ml), and from 4.9 to 82.3 mU/ml (median 20.4 mU/ml) in parenterally dosed animals. No increase in haematocrit or reticulocyte count was noted in enterally treated pups compared with controls after up to two weeks of treatment. Small bowel length was greater in rEpo treated pups, and a dose dependent increase in villus surface area which was independent of the route of dosing and associated with increased BrdU uptake was found.
  
  
  CONCLUSIONS
  rEpo is not enterally absorbed in an intact and functional form from the intestines of neonatal rat pups. Thus enterally dosed rEpo has no erythropoietic effects. However, rEpo acts as a trophic factor in developing rat small bowel whether given enterally or parenterally.
authors.affiliation: Department of Pediatrics, University of Florida College of Medicine, Florida, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Juul
authors.forename: D J
authors.initials: DJ
authors.lastname: Ledbetter
authors.forename: A E
authors.initials: AE
authors.lastname: Joyce
authors.forename: C
authors.initials: C
authors.lastname: Dame
authors.forename: R D
authors.initials: RD
authors.lastname: Christensen
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: V
authors.initials: V
authors.lastname: DeMarco
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D004186:Disaccharidases / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D006400:Hematocrit; D007091:Image Processing, Computer-Assisted; D007408:Intestinal Absorption / Q000502:physiology; D007422:Intestines / Q000187:drug effects* / Q000254:growth & development; D016014:Linear Models; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D017701:Reticulocyte Count
chemical_list: D011994:Recombinant Proteins; D004921:Erythropoietin; D004186:Disaccharidases; D001973:Bromodeoxyuridine