Hormones and the Lung. III. Thyroid Hormone Uptake Kinetics of Perinatal Rat Lung*

Hitchcock, Karen R.; Harney, John W.; Reichlin, Seymour

doi:10.1210/endo-107-1-294

Cited by 17 publications

(6 citation statements)

References 36 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: 77%

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: 77%

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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“…The pattern of onto genetic changes in plasma concentration of thyroid hormones during the perinatal period in rabbit is similar to that in the rat [2]. However, in the human the peak plasma-free T4, total T4 or T3 concentration during the perinatal period is observed within the first 24 h of life [20][21][22].…”

Section: Discussionmentioning

confidence: 99%

“…Development of fetal lung, mechanisms involved in neonatal thermogenesis and glucose homeo stasis are particularly influenced by thyroid hormones [1][2][3][4][5][6][7][8]. Maturation of these homeostatic mechanisms is essential for an independent extrauterine survival.…”

Section: Introductionmentioning

confidence: 99%

Ontogeny of Plasma-Free Thyroxine and Triiodothyronine Concentrations during the Perinatal Period and Maternofetal Transfer of Thyroid Hormones in the Rabbit

Up¹,

Su²,

Hf³

et al. 1986

Dev Pharmacol Ther

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Although rabbit has been used as a convenient animal model in understanding the role of thyroid hormones during the perinatal development, ontogenetic changes in plasma-free thyroxine or triiodothyronine concentration has not been studied in this species. We delineated the ontogeny of immunoreactive plasma-free thyroxine and triiodothyronine concentration during the perinatal period. It is generally believed that thyroid hormones do not cross the placenta from the mother to the fetus in sufficient concentrations to exert biological effects in the fetus. We administered 250 pg/kg of thyroxine (T4) or 125 pg/kg of triiodothyronine (T3) intramuscularly to the rabbit doe on the 25th and 26th day of gestation. Maternal and fetal plasma-free T4, T3 and glucose concentration and fetal liver glycogen content were quantitated on the 27th day of gestation. Maternal and fetal plasma-free T4 and T3 concentration was significantly higher than the control in T4-treated animals. Maternal and fetal plasma T3 concentration was higher and free T4 concentration lower than the control in T3-treated animals. T3 or T4 treatment resulted in fetal hyperglycemia and depletion of fetal hepatic glycogen content. We conclude that T4 or T3 cross the rabbit placenta and exert thyromimetic effects in the fetus. A convenient animal model to investigate in utero effects of T4 or T3 in mammalian fetal development is proposed.

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“…Although the physiologic importance of this T3 neogenesis remains unclear, it is quite possible that T3 exerts the biologic effects of thyroid hormone and, therefore, is responsible for the morphologic changes in fetal and adult type I1 cells which have been described by a number of investigators (for review, see [20][21][22]. It is also possible that T4, rather than acting as a prohormone, has effects of its own, and that in the course of its activity it is metabolized peripherally to other thyronines such as T3 and rT3 These compounds might then simply represent by-products of thyroid hormone action.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, Hitchcock and collaborators (20)(21)(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.…”

mentioning

confidence: 99%

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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Hormones and the Lung. III. Thyroid Hormone Uptake Kinetics of Perinatal Rat Lung*

Cited by 17 publications

References 36 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.

Ontogeny of Plasma-Free Thyroxine and Triiodothyronine Concentrations during the Perinatal Period and Maternofetal Transfer of Thyroid Hormones in the Rabbit

Thyroxine Metabolism in Cultured Cells Derived from Fetal Rat Lung

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