Journal of Clinical Endocrinology & Metabolism, Vol 53, 21-28, Copyright © 1981 by Endocrine Society

ARTICLES

Identification and characterization of nuclear 3,5,3'-triiodothyronine- binding sites in fetal human lung

LW Gonzales and PL Ballard

Thyroid hormones have been implicated in the prenatal lung development of several species. To investigate the possibility that thyroid hormones could play a role in human lung development, we examined nuclei from fetal human lung for the presence of high affinity T3- 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 weeks of gestation. The T3-binding capacity increased 65% between 12- 13 weeks (binding capacity, 0.227 and 0.282 fmol/micrograms DNA in two experiments) and 16-19 weeks of gestation [binding capacity, 0.420 +/- 0.014 (SEM) fmol/micrograms DNA; n = 8]. Maximal binding was achieved after 4 h of incubation at 20 C. The half-times for dissociation of the T3-receptor complex were 36 h, 10.5 h, 3 h, and 23 min at 2, 20, 25, and 37 C, respectively. The relative order of potency of thyroid hormone analogs in displacing L-T3 from the receptor was: T3- proprionate greater than 3.3'-5-triiodothyroacetic acid greater than L- T3 greater than D-T3 greater than L-T4 greater than 3,5-diethyl-3'- isopropyl-D,L-thyronine greater rT3 greater than 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 C). This release increased with incubation time and temperature, but was independent of T3 concentration, Ca2+, and gestational age. Incubation at 37 C also inactivated some of the receptors, but T3 provided dose-dependent protection from this loss of binding activity. Our results are consistent with the proposal that nuclear receptors mediate a direct effect of thyroid hormones on developing human lung as early as the second trimester of gestation.

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