title: Regulation of the hepatic transferrin receptor in hereditary hemochromatosis.
abstract: The liver is the main site of iron accumulation and pathologic sequelae in hereditary hemochromatosis. Whether this is a result solely of inappropriately increased absorption of iron by the gastrointestinal tract or a more generalized regulatory failure of iron balance is unknown. Using immunohistochemical techniques, we have examined the effects of therapeutic changes in liver iron stores on the expression of the hepatic transferrin receptor in hereditary hemochromatosis. Ten patients with untreated hereditary hemochromatosis had no detectable staining for transferrin receptor in their liver biopsies. All had increased hepatic ferritin (mean = 19.9 micrograms per mg protein, range = 1 to 31.7 micrograms per mg protein) and hepatic iron levels (mean = 36.2 micrograms per mg protein, range = 3.6 to 69.9 micrograms per mg protein). In contrast, hepatocyte transferrin receptor was detected in seven patients in whom hepatic iron stores were markedly depleted by venesection (hepatic ferritin mean = 0.32 microgram per mg protein, range = 0.16 to 0.53 microgram per mg protein; hepatic iron mean = 0.98 microgram per mg protein, range = 0.3 to 2.1 micrograms per mg protein). Sequential data from one patient confirmed the reexpression of receptor in response to therapeutic iron depletion, whereas data from another patient studied during treatment illustrated a reciprocal relationship between liver tissue distribution of iron and expression of transferrin receptor. The finding that appropriate physiologic regulation of the hepatic transferrin receptor operates in hereditary hemochromatosis does not support the concept of a generalized defect in receptor-mediated uptake of transferrin-bound iron.
authors.affiliation: Liver Unit, Kings College Hospital, London, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Lombard
authors.forename: A
authors.initials: A
authors.lastname: Bomford
authors.forename: M
authors.initials: M
authors.lastname: Hynes
authors.forename: N V
authors.initials: NV
authors.lastname: Naoumov
authors.forename: S
authors.initials: S
authors.lastname: Roberts
authors.forename: J
authors.initials: J
authors.lastname: Crowe
authors.forename: R
authors.initials: R
authors.lastname: Williams
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D006432:Hemochromatosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism*; D014168:Transferrin / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D011990:Receptors, Transferrin; D014168:Transferrin; D007501:Iron