Hormones and the lung II. Immunohistochemical localization of thyroid hormone binding in type II pulmonary epithelial cells clonally‐derived from adult rat lung

Wilson, Marjorie; Hitchcock, Karen R.; Douglas, William H.; DeLellis, Ronald A.

doi:10.1002/ar.1091950404

Cited by 19 publications

(4 citation statements)

References 23 publications

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“…which is produced in the mesenchyme under glucocorticoid regulation. This view is supported by observations of nuclear T3 receptors in cultured alveolar epithelial cells (15,16) and of preferential uptake of T3 by the perinatal rat lung (17). Further evidence that, in contrast to that of cortisol, T3 action is directly on the epithelium is our observation that T3 has no effect on FPF production by the mesenchyme, either alone or in combination with cortisol.…”

supporting

confidence: 76%

Glucocorticoid-thyroid synergism in lung maturation: a mechanism involving epithelial-mesenchymal interaction.

Smith¹,

Sabry²

1983

Proc. Natl. Acad. Sci. U.S.A.

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We studied the effects of cortisol and triiodothyronine (T3) on 20-day fetal rat lung cell cultures. Cortisol -enhanced the production of surfactant-associated saturated phosphatidylcholine while T3 did not. However, T3 potentiated the cortisoleffect. We observed that T3 enhanced the response of cultures enriched-with alveolar type 11 cells to fibroblast-pneumonocyte factor (FPF). Intracellular cAMP was increased by exposure of these cultures to FPF, and T3 potentiated this increase. Unlike cortisol, T3 had no effect on production of FPF by fetal lung fibroblasts, as determined by bioassay of fractions of fibroblastconditioned medium partially purified by column chromatography. The time. course of cortisol action on mixed (fibroblast/epithelial) cultures was in keeping with the proposed mechanism: glucocorticoid induction of FPF in fibroblasts, followed by FPF induction of cAMP 'in epithelia and, 'finally, by enhanced production of saturated phosphatidylcholine. Thus, glucocorticoid acting on mesenchyme and thyroid hormone acting on epithelium have a synergistic effect on expression of differentiated epithelial function.In late fetal life, maturation of the mammalian lung is heralded by the ability of alveolar epithelial type II cells to synthesize and secrete the pulmonary surfactant, which is necessary for successful postnatal gas exchange (1). Extensive evidence suggests that both glucocorticoids and thyroid hormones regulate surfactant synthesis in late fetal life. Glucocorticoids enhance surfactant-associated phospholipid synthesis by fetal lung in organ culture (2-4) or in mixed monolayer culture (5, 6), but their effect on clonally derived alveolar type II cells is very much attenuated (7). It is now evident that a major glucocorticoid effect on the alveolar epithelium is indirect: glucocorticoid (cortisol) induces production by fetal lung fibroblasts of fibroblastpneumonocyte factor (FPF), which, in turn, increases phospholipid synthesis by alveolar epithelial type II cells in vitro (7) and in vivo (8). We here report that triiodothyronine (T3) acts directly on alveolar type II cells to enhance responsiveness to FPF.MATERIALS AND METHODS Cell Cultures. All cultures were prepared from 20-day fetal rat lungs. Mixed monolayer cultures were prepared as described (5), modified as follows: mixed cell suspensions were prepared by incubating finely minced lung in Ca2"-, Mg2+-free Hanks' balanced salt solution containing 0.05% trypsin (Worthington), DNase (10 pg/ml; Sigma), and 1% chicken serum (GIBCO) (9). They were plated in 24-well plates (10) at high cell density (4 x 106 cells.per cm2) and maintained in 2 ml of minimal essential medium/10% newborn calf serum for 3 days with daily medium changes.Cultures enriched with respect to alveolar type II cells were prepared as described above, except that 2 hr after initial plating, -at which time a majority of the fibroblasts had attached to the flask (11), the supernatant media were aspirated with unattached cells. The cells were pelleted at 50 x g and the ...

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supporting

confidence: 76%

Glucocorticoid-thyroid synergism in lung maturation: a mechanism involving epithelial-mesenchymal interaction.

Smith¹,

Sabry²

1983

Proc. Natl. Acad. Sci. U.S.A.

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“…These findings corroborate the results of irnmunohistochemical studies which have demonstrated T3 in type I1 cells in culture (37), and studies that have demonstrated the existence of specific nuclear T3 receptors in cultured fetal rabbit (3) and human (17) lung cells.…”

Section: Discussionsupporting

confidence: 89%

Thyroxine Metabolism in Cultured Cells Derived from Fetal Rat Lung

et al. 1983

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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 ...

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“…Our results support this concept in that we observed significant associations in preterm infants between TSH levels and RDS and sepsis. The effect of thyroid hormones on RDS has been extensively studied as thyroid hormones are regulators of surfactant metabolism, and surfactant insufficiency results in RDS (14–16). Several studies have shown an association between low TSH and RDS; however, the results have been inconsistent (6, 17–20).…”

Section: Discussionmentioning

confidence: 99%

“…Experimental and animal models demonstrate that thyroid hormones regulate surfactant metabolism (14–16). Surfactant insufficiency is associated with neonatal respiratory distress syndrome (RDS) which can occur in both preterm and term infants.…”

Section: Introductionmentioning

confidence: 99%

Maternal factors and complications of preterm birth associated with neonatal thyroid stimulating hormone

Ryckman

Spracklen

Dagle

et al. 2014

Journal of Pediatric Endocrinology and Metabolism

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Thyroid hormones are important regulators of fetal neurodevelopment. Among preterm infants, TSH is highly variable. Understanding this variability will further improvements in screening for thyroid disorders in preterm infants. We examined 61 maternal and infant clinical and demographic factors for associations with neonatal TSH levels in 698 preterm neonates. TSH was measured as part of routine State-mandated newborn screening in Iowa. Of the maternal characteristics, nulliparous women (P=8x10−4), women with preeclampsia (P=2x10−3), and those with induced labor (P=3x10−3) had infants with higher TSH levels. TSH levels at the time of newborn screening were associated with respiratory distress syndrome (RDS) (P<0.0001) and sepsis (P=3x10−3). We replicated findings between parity and preeclampsia previously observed in primarily term infants. We also observed strong relationships between neonatal TSH and complications of prematurity including RDS and sepsis, which has implications for future studies examining this relationship both prenatally and longitudinally after birth.

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Hormones and the lung II. Immunohistochemical localization of thyroid hormone binding in type II pulmonary epithelial cells clonally‐derived from adult rat lung

Cited by 19 publications

References 23 publications

Glucocorticoid-thyroid synergism in lung maturation: a mechanism involving epithelial-mesenchymal interaction.

Glucocorticoid-thyroid synergism in lung maturation: a mechanism involving epithelial-mesenchymal interaction.

Thyroxine Metabolism in Cultured Cells Derived from Fetal Rat Lung

Maternal factors and complications of preterm birth associated with neonatal thyroid stimulating hormone

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