The role of serum binding proteins in determining free thyroid hormone concentrations during development in quail

Japanese quail were used as a model for studying the role of binding proteins in determining free T4 (FT4) and free T3 (FT3) concentrations during development. Adults were used to characterize thyroid hormone binding; developmental stages studied were late embryonic, perinatal, hatchling, and juvenile. Total and free hormones were determined directly by RIA, and free hormones were determined indirectly by equilibrium dialysis. Binding proteins were identified by electrophoresis of serum preincubated with labeled hormones. Serum FT4 and FT3 concentrations in adult quail were equivalent to those in humans. T4 bound principally to albumin and secondarily to prealbumin; T3 bound principally to alpha-globulin and secondarily to albumin and gamma-globulin. A specific T4-binding globulin, as in mammals, was not present. The relative affinity of stripped serum was greater for T4 than for T3. In late embryos, FT4 concentrations rise as a result of a marked increase in total T4 (TT4) and modest increases in binding proteins. The perinatal peak in FT4 reflects the perinatal surge of TT4 without a change in binding proteins. From days 1-6 posthatching, FT4 decreases as a consequence of TT4 decreasing faster than the decrease in binding. In juveniles, FT4 concentrations stabilize as increases in TT4 are paralleled by increases in serum binding. T3 binding shows few significant differences from adult values during development, so FT3 concentrations follow closely the pattern of TT3 changes. These results demonstrate that developmental changes in serum binding proteins play a significant role in determining the pattern of free thyroid hormones, especially for FT4, by modulating the total hormone concentrations controlled by the hypothalamic-pituitary axis.