Thyroxine Metabolism in Cultured Cells Derived from Fetal Rat Lung

Abstract

SummaryThe role of thyroxine (T4) in fetal lung development has been demonstrated previously. Because triiodothyronine (T3), not T4, is thought to be the active hormone, and because T3 nuclear recep tors appear to be present in fetal lung, the following studies were performed to examine peripheral metabolism of [12'I] [1311JT3 and [1251]T3; the ratio of these provided an index of intracellular conversion of [12'I]T4 to [l2'IjT3. The mean of five such experiments demonstrated that of the total ['2'IJT3 attached to the nuclear fraction at the end of the incubation, 32% was newly generated and 68% was derived by influx from the medium. These results indicate that organotypic cultures derived from day 19 fetal rat lung are capable of deiodinating T4 and that both rT3 and T3 are generated. The generated T3 appears to be retained by the lung cells and is bound to the nuclear fraction. On the other hand, rT3 is distributed more evenly throughout the cell and in the medium and presumably is not bound. Abbreviations DIMIT, 3,5-dimethyl-3'-isopropyl-L-thyronine FBS, fetal bovine serum PC, phosphatidylcholme T3, triiodothyronine rT3, reverse T3 T4, thyroxine TAA, hexane-tertiary amyl alcohol3 N ammoniaThe role of thyroid hormone in fetal lung development is well recognized, but its mechanism of action is not clear (20-22, 27, 38). The hormonal milieu of the mammalian fetus is characterized by low triiodothyronine (T3) levels and high concentrations of reverse T3 (rT3) (16, 38); and yet, certain target organs, including the lung, appear to depend on the active form of thyroid hormone (i.e., T3) during certain developmental stages.Early studies by Redding et al. (27) showed that thyroidectomy and subsequent thyroid hormone replacement profoundly influenced the morphologic characteristics of type I1 pneumonocytes and their lamellar bodies, and that there was a correlation between the demonstrated ultrastructural changes and lung surfactant secretion. More recently, Hitchcock and collaborators (20-22) demonstrated that thyroxine (T4) can accelerate rat lung development and that this acceleration is maximal in the presence of glucocorticoids. Similar findings were noted by Ballard and associates (1, 2) during transplacental stimulation of fetal rabbit lung by an analog of T4 known as DIMIT. The effects of hormones on fetal lung metabolism have also been studied using fetal lung cells under conditions of short term monolayer culture. smith and Torday (33), using monolayer cultures of fetal rabbit lung cells, found that T4 produced a significant increase in incorporation of [14C]-choline into PC. In a similar tissue culture system, Farrell et al. (14) have shown an increase in activity of cholinekinase, and both T4 and cortisol exposure led to an increase in choline phosphotransferase.With the increasing evidence that most, if not all, actions of thyroid hormone are expressed by T3, there have been additional investigations of the effect of T3 on lung development. Using organotypic cultures of fetal rat lung alveolar type I1 ...