title: Bioavailability of granulocyte colony-stimulating factor administered enterally to suckling mice.
abstract: The developing fetal and neonatal gastrointestinal (GI) tract is influenced by many growth factors, including epidermal growth factor (EGF), insulin-like growth factor (IGF), transforming growth factor (TGF), and erythropoietin (Epo). Granulocyte colony-stimulating factor (G-CSF), typically regarded as a hematopoietic growth factor, might also be included because it exists in high concentrations in amniotic fluid, colostrum, and human milk, and because granulocyte CSF receptors (G-CSF-R) are abundantly expressed on the villous enterocytes of the developing intestine. As a first step toward understanding whether the effects of G-CSF on the GI tract were local or systemic, we sought to determine whether recombinant human G-CSF (rhG-CSF) administered enterally to suckling mice, is absorbed into the circulation, and if so, whether the G-CSF-R is essential for this absorption. We enterally administered rhG-CSF to suckling mice, selecting a daily dose based on the amount of G-CSF normally swallowed by the fetus and neonate (3 ng), or in other mice, a dose of G-CSF 100 times larger (300 ng). Pups were tested at either 5-7 days of age, or at 14-16 days of age. C57BL/6 x 129SvJ mice were used. Some mice had a targeted null mutation in the G-CSF-R gene, producing a non-functional G-CSF-R protein. At intervals following the enteral G-CSF dosing, G-CSF concentrations in plasma were measured by specific ELISA. The bioavailability of G-CSF was invariably <1%, regardless of the dose of rhG-CSF given, the age of the pups, or whether they had a functional G-CSF-R. After enteral administration of rhG-CSF to suckling mice, only minimal quantities of G-CSF are absorbed into the circulation, and the G-CSF-R is not essential for this absorption.
authors.affiliation: Department of Pediatrics, Division of Neonatology, University of Florida, Gainesville, FL 32610-0296, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Gersting
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Kotto-Kome
authors.forename: Yan
authors.initials: Y
authors.lastname: Du
authors.forename: Robert D
authors.initials: RD
authors.lastname: Christensen
authors.forename: Darlene A
authors.initials: DA
authors.lastname: Calhoun
mesh_terms: D000367:Age Factors; D000818:Animals; D000833:Animals, Suckling / Q000378:metabolism*; D019540:Area Under Curve; D001682:Biological Availability; D004750:Enteral Nutrition / Q000379:methods; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins
chemical_list: D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor