Roles of erythropoietin in human milk

Abstract

Erythropoietin (Epo) is one of many biologically active growth factors present in human and animal milk. Accumulating evidence shows important developmental roles for these milk‐borne growth factors. Although Epo is present in biologically relevant amounts in mammalian milk, the roles of Epo in milk are incompletely defined. A significant proportion of milk‐borne Epo resists proteolytic degradation. Epo receptors (EpoR) have been found on gastric mucosa and intestinal mucosa, and in mesenteric vessel endothelium. Evidence to date shows that intact Epo reaches these local organs, as well as distal organs. After feeding Epo, local gastrointestinal physiological effects are seen in suckling rats. In humans and rats, short‐term feeding of high‐dose Epo increases reticulocytes, but it is unclear whether sustained treatment increases red cell mass. Conclusion: Further work towards understanding the physiological and potential pharmacological roles of enterally administered Epo is necessary. Summary Evidence to date supports the theory that Epo is present in biologically relevant amounts in mammalian milk, is protected from gastrointestinal proteolytic degradation and probably plays a role in local neonatal gastrointestinal development. Animal data show that milk from hypoxic mothers appears to stimulate erythropoiesis better than pharmacological doses of Epo added to normal milk or formula. The lack of efficacy of pharmacological doses of rhEpo in studies to date may be secondary to several factors, including local utilization of the hormone, the need for Epo to work in conjunction with another hematopoietic growth factor in milk, or nutritional factors, such as iron deficiency, interfering with the rhEpo response. Whether milk‐borne Epo plays a significant role in stimulating erythropoiesis is still unclear and more work is necessary to determine the physiological and pharmacological roles of milk‐borne Epo.

Erythropoietin: A Hormone with Multiple Functions

“…High concentrations of EPO are present in human milk [71][72][73] and milk from other species, such as the rat [74] , suggesting that it plays a role in the erythropoiesis, neurodevelopment, and gut maturation of neonates. …”

Erythropoietin and Its Receptor in Breast Cancer: Putting Together the Pieces of the Puzzle

“…3), after Epo binding, the heterodimeric EpoR complex may be efficiently internalized without either the binding/activation/phosphorylation of JAK2 or the ubiquitination process, thus not involving the protein kinase cascade/network [41,48]. The internalization process of the Epo-EpoR complex probably occurs either by conformational changes induced by Epo binding or by caveolae/ clathrin-dependent pathway(s).…”

Characterization of Developing Bowel Transplanted from Transgenic Erythropoietin Receptor-Deficient Mouse Embryos

“…Functional erythropoietin (Epo) receptors (EpoR) are present in developing human and rodent bowel, and activation of EpoR signaling by recombinant Epo (rEpo) has trophic and antiapoptotic effects in cultured enterocytes, and neonatal rat bowel [1][2][3][4] . Endogenous Epo is thought to work in concert with other somatic growth factors to influence the growth and development of fetal organs that express EpoR [5] .…”

“…Fetal enterocytes are exposed to circulating Epo, and to intraluminal Epo from amniotic fluid that is continually swallowed by the fetus [11,12] . Postnatal exposure continues from Epo in breast milk [4,10,13] . Thus, the EpoR is present on enteric cells, the receptor is functional, and Epo is available during both preand postnatal development.…”