Changes in the expression of intestinal iron transport and hepatic regulatory molecules explain the enhanced iron absorption associated with pregnancy in the rat

• Published in: Gut 2004-05, Vol.53 (5), p.655-660
• Main Authors: Millard, K N, Frazer, D M, Wilkins, S J, Anderson, G J
• Format: Article
• Language: English
• Subjects: Animals; Antimicrobial Cationic Peptides - metabolism; Biological and medical sciences; Cation Transport Proteins - metabolism; Dcytb; divalent metal transporter 1; DMT1; duodenal cytochrome b; Duodenum - metabolism; Female; Fetuses; GAPDH; Gastroenterology. Liver. Pancreas. Abdomen; Gene expression; glyceraldehyde 3-phosphate dehydrogenase; Hemochromatosis Protein; Hepcidins; hephaestin; hereditary haemochromatosis; HFE; Histocompatibility Antigens Class I - metabolism; Homeostasis - physiology; Intestinal Absorption - physiology; IRE; Ireg1; Iron; Iron - metabolism; iron regulated mRNA (also known as ferroportin 1); iron regulation; iron responsive element; Iron-Binding Proteins - metabolism; Liver - metabolism; Medical research; Medical sciences; Membrane Proteins - metabolism; Metabolism; non-pregnant; Placenta; post-partum; Pregnancy; Pregnancy, Animal - metabolism; Pregnancy, Animal - physiology; Protein expression; Proteins; Rats; Rats, Sprague-Dawley; Receptors, Transferrin - metabolism; ribonuclease protection assay; Rodents; RPA; Small Intestine; Studies; TfR; the gene mutated in the most prevalent form of hereditary haemochromatosis; transferrin receptor
• ISSN: 0017-5749; 1468-3288; 1458-3288
• DOI: 10.1136/gut.2003.031153

Background: Iron absorption increases during pregnancy to cater for the increased iron requirements of the growing fetus. Aims: To investigate the role of the duodenal iron transport molecules and hepatic regulatory molecules in coordinating the changes in iron absorption observed during pregnancy. Methods: Rats at various days of gestation and 24–48 hours post-partum were examined for hepatic expression of hepcidin, transferrin receptors 1 and 2, and HFE (the gene mutated in the most prevalent form of hereditary haemochromatosis), and duodenal expression of divalent metal transporter 1 (DMT1), duodenal cytochrome b (Dcytb), iron regulated mRNA (Ireg1), and hephaestin (Hp) by ribonuclease protection assay, western blotting, and immunohistochemistry. Results: Decreased hepatic non-haem iron and transferrin saturation and increased expression of transferrin receptor 1 in the liver indicated a progressive reduction in maternal body iron stores during pregnancy. Duodenal expression of the iron transport molecules DMT1, Dcytb, and Ireg1 increased during pregnancy, and this corresponded with a reduction in hepcidin, HFE, and transferrin receptor 2 expression in the liver. Expression of all molecules returned towards control values by 24–48 hours post-partum. Conclusions: These data indicate that increased expression of key iron transport molecules is responsible for the elevated iron absorption associated with pregnancy, and implicate hepcidin, HFE, and transferrin receptor 2 in determining how the maternal iron homeostatic machinery responds to the increased iron demands accompanying gestation.