Triiodothyronine Nuclear Binding in Fetal and Adult Rabbit Lung and Cultured Lung Cells*

Abstract

To investigate the possible mechanism of thyroid hormone action in the lung, we examined fetal and adult rabbit lung, and cell lines derived from lung, for specific nuclear binding sites for T3. Using incubation of isolated nuclei with L-[125I]T3 at 37 C, we found approximately 2400 specific binding sites/cell in fetal lung and 1120 sites/cell in adult lung, with a similar dissociation constant (approximately 500 pm) for both tissues. The L-2 and A549 cell lines, which may have originated from pulmonary type II alveolar cells, contained 2280 and 1580 nuclear sites/cell, and the dissociation constants were 280 and 200 pm, respectively. In fetal lung, the ability of various analogs to compete for L-T3 (100%) binding was: 3,5-diiodo-3'-isopropylthyronine, 81%; D-T3, 73%; L-T4, 6.7%; 3,3'-diiodothyronine, 0.19%; 3,5-dimethyl-3'-isopropyl-L-thyronine, 0.15%; and rT3, 0.08%. These findings indicate that both fetal and adult lung, and cultured lung cells, contain specific nuclear binding sites for T3, suggesting that these tissues and their type II alveolar cells may be directly influenced by thyroid hormones.

Characterization of Nuclear 3,5,3′-Triiodothyronine Receptors in the Developing Rat Lung: Effects of Hypo- and Hyperthyroidism

“…The data presented herein confirm and extend previous observations on the presence of nuclear T3 receptor in the lung (23,26). In all ages studied, we found a single class of binding sites with a mean Ka of 1.16 + 0.05 x 10'' M-I, which is slightly higher than that reported earlier.…”

“…The decrease of Ka that we observe with age is concomitant with the increase of the saturation level and so, might be due to the presence of endogenous hormone since our binding assays are not performed at complete equilibrium. The specificity of the nuclear receptor, as judged by the relative affinities of thyroid hormone analogs, is in general agreement with data previously reported for lung and other organs (22,23,26). The relative affinity of DIMIT for the nuclear receptor is of interest since, in contrast with T3 and T4 (1 1, 12), it crosses the placental barrier (7).…”

“…The presence of such receptors has recently been described in lungs of both fetal and adult rodents (23,26), suggesting that thyroid --hormones might act directly on the lung.…”

Effects of cortisol and thyroxine on phosphatidylcholine and phosphatidylglycerol synthesis by adult rat lung alveolar type II cells in primary culture

“…In type II cells corticosteroid [18] and thyroid hormone [19] receptors have been demonstrated indicating that type II cells may be influenced by a direct action of these hormones. Studies with isolated type II cells have shown that glucocorticosteroids stimulate the synthesis of phosphatidylcholines from radioactive precursors [20-221. However, the latter type of study has thus far only been carried out with cell line A549, derived from a human lung carcinoma [20] and with cells isolated from normal lung tissue by cloning [21,22].…”

On the pulmonary toxicity of oxygen. 4. The thyroid arena

“…But to take this to a deeper level, it should be noted the number of specific nuclear T 3 receptors in the lung, as the peripheral action site for thyroid effects on lung, varies in the rabbit. Lindenberg, et al, (1978) found 2400 specific binding sites per pulmonary cell in the fetus contrasted to 1120 sites per adult lung cell. Thus, size or size ratios have to be considered as an indirect marker for functional capacity as a rule, but when the data base is large and the trend is consistent in one direction, then greater weight may be placed on the result.…”