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Antigenic material in rat plasma reacting with rat transferrin receptor antibodies was identified as an intact receptor molecule complexed with transferrin. Plasma transferrin receptors were measured by ELISA in rats of different age and sex, of different iron status, with different degrees of erythropoiesis, and with inflammation. An inverse relationship between iron status and receptor number was found, whereas a direct relationship existed between erythropoiesis and receptors. These changes in receptor number can be explained by assuming that the number of tissue receptors determined the number of plasma receptors and that the erythroid cells possessed most of the body's receptors. Increases in plasma receptors lagged behind the appearance of circulating reticulocytes, suggesting that receptors were released to the plasma during the terminal phase of erythrocyte maturation.Iron-bearing transferrin in the plasma interacts with specific membrane receptors to deliver iron to cells (1). The process involves the internalization of the complex in a vesicle, the liberation of the iron to the cell's cytoplasm, and the return of the receptor to the cell membrane and of transferrin to the plasma (2). It is well documented in cell culture that the number of cell receptors bears an inverse relationship to the cell's iron status (3). Most of the in vivo transferrin-mediated iron uptake is by the erythroid marrow, so that tissue is assumed to contain most of the functional transferrin receptors and changes in erythropoiesis would affect receptor number. Studies by Kohgo et al. (4) have demonstrated material in human plasma, presumably transferrin receptor, that reacts with receptor antibodies. Kohgo has also shown increases in the amount of plasma receptor material in patients with hemolytic anemia and iron deficiency (5). In this study, we describe the presence in rat plasma of a receptortransferrin complex, reacting with either receptor or transferrin antibody. Results of a quantitative assay of plasma receptor levels under a variety of conditions are reported. METHODSReceptor Characterization Procedures. Electrophoresis was carried out in an electrophoretic cell model 155 (Bio-Rad, Richmond, CA), using 7.5% polyacrylamide gels in a column of 1.4 x 12 cm. 59Fe-labeled rat plasma samples (0.3 ml) were subjected to electrophoresis for 20 hr at 80 V. Thereafter, the gel was cut in slices of 2-mm thickness. The content of each slice was eluted for 48 hr in 1 ml of 0.9o saline containing 0.4% TERIC, and analyzed for receptor content by ELISA. 59Fe was counted in a Packard model 5330 y counter (Packard Instruments).Anti-transferrin antibodies were produced after immunization of rabbits as described (6, 7). Crossed immunoelectrophoresis was carried out by standard procedures (7).Quantitative Measurement of Transferrin Receptors. Antibody production was undertaken by using rat placental receptor-transferrin complexes isolated as described elsewhere (1). The complex had the advantage of possessing greater stability tha...

When exposed to an ambient temperature of 4 degrees C, iron-deficient anemic rats become hypothermic. This lesion is related more to anemia than to tissue iron deficiency, since exchange transfusion to hematocrits over 25 restored normal thermoregulatory performance. Likewise poor cold responses were induced in control rats by transfusion to low hematocrits. Cold sensitivity in all anemic animals was paralleled by poor thyroid responses: there was a significant positive correlation between hematocrit and percent rise in triiodothyronine (r = 0.63) and thyroxine (r = 0.53) during 6 h at 4 degrees C. Basal levels of thyroid-stimulating hormone (TSH) were similar in control and iron-deficient animals: after cold exposure, TSH rose to higher levels in those animals with hematocrits over 25 than in those with lower hematocrits. Diminished O2 delivery to tissues responsible for heat production is probably a major component of the cold sensitivity of anemic rats. The novel finding that thyroid hormone responses are compromised by anemia implies effects on hormonal regulation that may also contribute to this functional lesion.

Most of the references quoted are from the work of research fellows over the past 30 yr. This topic was chosen in order to acknowledge their outstanding contributions and to express my personal gratitude for the privilege of working with them.