- Holm, Ann-Charlotte
Membrane transport of triiodothyronine : With particular reference to erythrocytes in health and disease
Doktorsavhandling (övrigt vetenskapligt)abstract
- Cellular T3 uptake was studied in three human cell systems, i.e. cultured lymphocytes, erythrocytes and erythrocyte membrane vesicles.The basic experimental procedure included 1) incubation of cells or membranes with T3 tracer and increasing concentrations of unlabelled T3, 2) separation of unbound hormone from hormone bound to cells or membranes, 3) counting of radioactivity, and 4) calculation of saturable uptake and uptake constants. Variations on this basic experimental theme included a) addition of ATP or metabolic inhibitors, b) competition by T4 analogues, c) changes of vesicular volume and permeability, and d) changes of membrane temperature. Finally, the T3 concentration in the erythrocytes was measured.The uptake of T3 proved to be carrier-mediated. In lymphocytes it seemed to be energy dependent, but not in erythrocytes, although erythrocyte membrane vesicles had the potential to respond with accelerated uptake to increased energy supply from ATP. The mean Vmax was increased in hyperthyroidism and decreased in hypothyroidism (both p<0.01), and one patient with thyroid hormone resistance had a V max value similar to those of hyperthyroid patients. In patients with low serum free T3 from non-thyroidal causes V max was not altered. The mean Km for T3 uptake in erythrocytes was similar in controls and the patient groups examined.Binding of T3 to the membrane sites occurred only in membranes exposed to 25 °C and subsequently to 0 °C. The mean Bmax thus measured was reduced in hypothyroidism (p<0.05).The mean erythrocyte T3 concentration was 220 pM in healthy subjects, !50 pM in pregnancy, approximately 190 pM in non-thyroidal illnesses and 60 pM in hypothyroidism (all p<0.01).The results show that I) human erythrocytes and lymphocytes take up T3 by carrier-mediated transport, 2) the rate of T3 uptake changes in thyroid diesease but not in pregnancy or nonthyroidal illness, and 3) the erythrocyte T3 concentration is reduced in pregnancy and nonthyroidalillness, as in hypothyroidism.