Nuclear thyroid hormone receptors: ontogeny and thyroid hormone effects in sheep.

Abstract

To investigate the mechanism(s) responsible for the paucity of fetal thyroid hormone effects, thyroid hormone nuclear receptor (T3NR) binding characteristics were quantified in liver and brain of fetal and neonatal sheep. Maximal binding capacities [MBC; mean +/- SE fmol 3,5,3'-triiodothyronine (T3)/mg DNA] in liver increased from values of 68 +/- 14 at 80 days gestation to 684 +/- 152 at term. Liver T3NR MBC in newborn and adult sheep were comparable to values in term fetuses. Liver T3NR binding affinities were similar in all animals, averaging 1.68 +/- 0.05 X 10(9) M-1. Brain T3NR MBC were comparable at all fetal ages studied (410 +/- 55 fmol T3/mg DNA), increasing to 1,517 +/- 315 fmol T3/mg DNA during the 1st postnatal week and returning to comparable fetal values (368 +/- 37 fmol T3/mg DNA) in the 3rd week after birth. Brain T3NR binding affinities were comparable in all animals studied (7.5 +/- 2.1 X 10(9) M-1), and the mean value was significantly greater than mean liver T3NR affinity. T3NR binding of T3 analogues in six term fetal animals were qualitatively similar for both brain and liver and showed T3 = triiodothyroacetic acid greater than thyroxine greater than reverse T3. Like T3 binding affinity, T3NR analogue binding affinities in brain tissue were five- to sevenfold greater than those in liver. Fetal hypothyroidism induced by thyroidectomy at either 99-107 or 129-132 days of gestation was not associated with changes in brain or liver T3NR binding characteristics. The heterogenous ontogeny and binding characteristics of brain and liver T3NR is compatible with the hypothesis that different thyroid hormone receptors are expressed in these tissues.