Erythropoietin acts as a trophic factor in neonatal rat intestine

Background - Erythropoietin (Epo) receptors are present on enterocytes of f etal and neonatal small bowel but the role of Epo in the bowel is not known . Aims - We tested the following hypotheses: (1) enterally dosed Epo is absor bed 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 dependant on the route of administration. Methods - The dose dependant effects of enterally dosed recombinant human e rythropoietin (rEpo 0-1000 U/kg/day) were studied in artificially raised ra t 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 (ente ral upsilon 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 in crease 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 associ ated with increased BrdU uptake was found. Conclusions - rEpo is not enterally absorbed in an intact and functional fo rm from the intestines of neonatal rat pups. Thus enterally dosed rEpo has no erythropoietic effects. However, rEpo acts as a trophic factor in develo ping rat small bowel whether given enterally or parenterally.