Distribution of Transferrin and Transferrin Receptors in the Rabbit Placenta

Abstract

SUMMARYThe quantity and distribution of transferrin and transferrin-binding sites in the placenta were investigated in rabbits on the 28th-29th days of pregnancy. The animals were injected intravenously with a mixture of 59Fe-121I-labelled rabbit diferric transferrin and 131I-labelled rabbit albumin. The binding of transferrin to placentas removed 3-75 min later was determined by using the 13II-labelled albumin values to correct for tissue content of plasma. Mean values for transferrin binding of 1460 and 560 ,ug/g tissue were obtained 3-15 and 45-75 min after injection, respectively. Gel filtration ofplacental extracts prepared with the non-ionic detergent, Teric 12A9, showed that the 125I-labelled transferrin bound to a large molecular weight component which had the properties of a specific receptor. The receptor had a higher affinity for differic transferrin than for apotransferrin. The subcellular distribution of transferrin binding sites was determined by differential centrifugation of placental homogenates and by electron microscope autoradiography. The results with the former method indicated that the transferrin was bound to the microsomal fraction of the cells. Autoradiography showed that the majority of the transferrin molecules were at intracellular sites, mainly on the membrane of intracellular vesicles. It is concluded that iron-containing transferrin molecules enter the trophoblast cells by endocytosis or via a canalicular system after binding to cell membrane receptors. The higher affinity of the receptors for diferric transferrin than for apotransferrin explains the difference in amount of transferrin binding found within 15 min of injecting labelled diferric transferrin and that found 45-75 min later when much of the iron had been removed from the transferrin.

Iron transport and storage

“…Further, the inhibition of iron uptake by inhibitors of endocytosis is proportional to the inhibition of transferrin endocytosis [l SO] and both transferrin and its receptor are recycled to the cell surface by exocytosis [181] with a recycling time of 3-4 min at 37°C [160]. That receptor binding [182] and endocytosis [183] is also involved in transferrin and iron uptake by placenta is also well established.…”

The placenta: the forgotten essential organ of iron transport

“…Immunohistochemical studies have localized TFR1 and transferrin to the apical membrane of syncytiotrophoblasts. 25,26 Concordantly, immunoelectron microscopy demonstrated the presence of transferrin [26][27][28] and TFR1 29 on the membrane of cellular invaginations and intracellular vesicles, likely representing clathrin-coated endosomes that contain transferrin, 30,31 TFR1, 32 and TFR1-transferrin complexes. 30,32 Kinetic studies in BeWo cells 33 and placental microvillous membrane preparations 17,34,35 showed that diferric transferrin uptake is a specific and saturable process, with binding affinities similar to values reported in K562 erythroleukemia cells 36 and reticulocytes.…”

Effects of nitrogen monoxide and carbon monoxide on molecular and cellular iron metabolism: mirror-image effector molecules that target iron

“…We are not proposing that Fe is exclusively released via ' CO-Fe '. Indeed, apo-Tf and the ferroxidase caeruloplasmin may facilitate Fe release [178,179].…”