The early ontogenesis of thyroid hormone receptor in the rat fetus.

Abstract

We have determined the concentration of thyroid hormone receptor binding sites in nuclear extracts derived from rat fetal organs throughout gestation and the postnatal period. Before day 14 of gestation nuclear extracts were obtained from whole fetuses. No receptor binding activity could be detected at day 12 of gestational age, and small amounts were detected at day 13 (maximum binding capacity less than 50 fmol/mg DNA). The receptor could be measured in pools of individual organs from day 14 (brain) or from day 16 (heart, liver, and lung) onwards. The order of analog binding affinity at 14 days was triiodothyroacetic acid = T3 greater than T4 greater than rT3, suggesting that at 14 days of fetal age the receptor has the same binding specificity as the receptor from mature tissues. In brain, the concentration of binding sites increased from 77 fmol/mg DNA at 14 days to 210 fmol/mg DNA at 17 days, remaining at this level until birth. Receptor concentration was identical whether the binding assays were performed on purified nuclei or nuclear extracts. There was no effect of maternofetal hypothyroidism on receptor concentration in the brain at 21 days of gestational age. Lung concentrations of receptor also remained constant during the fetal period. During the postnatal period, there was an increase in receptor concentration in brain and lung, with maximum levels at day 6. The pattern of receptor development in heart and liver was different, since its concentration increased progressively throughout the fetal and postnatal periods towards the levels found in adult rat tissues. The results suggest that the appearance of the thyroid hormone receptor coincides with that of the first fetal thyroid gland structures, but that it occurs much before thyroid function is fully established. As far as the receptor is concerned, fetal tissues have the potential to respond to thyroid hormone as early as the 13th day of gestational age.