Identification and Characterization of Nuclear 3,5,3′- Triiodothyronine-Binding Sites in Fetal Human Lung*

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Abstract
Thyroid hormones were implicated in the prenatal lung development of several species. To investigate the possibility that thyroid hormones could play a role in human lung development, nuclei from fetal human lung were examined for the presence of high affinity T3[triiodothyronine]-binding sites. A single class of high affinity (Kd = 35 .+-. 3 pM) binding sites for L-T3 was identified in nuclei from fetuses between 12-19 wk of gestation. The T3-binding capacity increased 65% between 12-13 wk (binding capacity, 0.227 and 0.282f[femto]mol/.mu.g DNA in 2 experiments) and 16-19 wk of gestation [binding capacity, 0.420 .+-. 0.014 (standard error of the mean) fmol/.mu.g DNA; n = 8]. Maximal binding was achieved after 4 h of incubation at 20.degree. C. The half-times for dissociation of the T3-receptor complex were 36, 10.5, 3 h and 23 min at 2.degree., 20.degree., 25.degree. and 37.degree. C, respectively. The relative order of potency of thyroid hormone analogs in displacing L-T3 from the receptor was: T3-propionate > 3,3''-5-triiodothyroacetic acid > L-T3 > D-T3 > L-thyroxine > 3,5-diethyl-3''-isopropyl-D''L-thyronine > reverse T3 > 3,5-dimethyl-3''-isopropyl-L-thyronine. Some receptors were released from the nuclei into the supernatant during incubation (7.8 .+-. 0.3% after 4 h at 20.degree. C). This release increased with incubation time and temperature, but was independent of T3 concentration, Ca2+ and gestational age. Incubation at 37.degree. C also inactivated some of the receptors, but T3 provided dose-dependent protection from this loss of binding activity. Nuclear receptors evidently mediate a direct effect of thyroid hormones on developing human lung as early as the 2nd trimester of gestation.