Development of fibroblast-type-II cell communications in fetal rabbit lung organ culture

doi:10.1016/0167-4889(92)90014-3

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

Volume 1175, Issue 1, 15 December 1992, Pages 95-99

https://doi.org/10.1016/0167-4889(92)90014-3 Get rights and content

Abstract

The development of the fetal lung is regulated by fibroblast-type-II cell communications which involve fibroblast pneumonocyte factor (FPF). FPF production is positively regulated by glucocorticoids and negatively regulated by dihydrotestosterone (DHT) and transforming growth-factor beta (TGF-β). We studied whether DHT or TGF-β affected other steps in the process of lung maturation, by studying how the developing lung in organ culture would respond to exogenously supplied FPF after DHT or TGF-β exposure. Fetal rabbit (day 19 of gestation) lung organ cultures were prepared and cultured in the presence of cortisol, DHT or TGF-β. After seven days, the media were replaced with serum-free medium containing either cortisol or FPF conditioned medium. The incorporation of [¹⁴C]glycerol into surfactant lamellar body DSPC was studied over 24 h as the index of surfactant synthesis. Results were compared to simultaneous control cultures. Treatment had no significant effect on tissue protein concentration or on the efficiency of lamellar body recovery. Cortisol stimulated baseline incorporation of glycerol into DSPC. This was inhibited by DHT, such that DHT plus cortisol treatment was no different from untreated controls. FPF stimulated the incorporation of glycerol into DSPC, and did so even after culture treatment with DHT. Cultures treated with TGF-β exhibited glycerol incorporation similar to untreated controls. After TGF-β exposure, FPF did not stimulate glycerol incorporation into DSPC. We conclude that DHT interferes with progression of lung development by delaying the appearance of FPF production by the fibroblast. TGF-β, on the other hand, inhibits other elements of lung maturation besides FPF production. We speculate that TGF-β interferes with type-II cell development such that the cell cannot respond to FPF.

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Lung maturation is delayed in male fetuses compared to female fetuses. This has been attributed to higher levels of androgens in the male lung. We previously showed that the genes encoding for the 17β-hydroxysteroid dehydrogenase (HSD) type 5 (conversion of androstenedione in testosterone) and type 2 (the opposite reaction) are, respectively, expressed in the human epithelial Type II (PTII)-like A549 cells and in human lung fibroblasts. Here, we aim to explain the physiological relevance of androgen synthesis by PTII cells. We showed that 17β-HSD type 2 and type 5 genes are both up-regulated in correlation with the emergence of mature PTII cells in both male and female developing lungs of the fetal mouse. In contrast, the androgen receptor gene is expressed at similar levels in both sexes with no temporal regulation. In conclusion, the expression profile of the 17β-HSD type 5 gene does not explain the presence of higher levels of androgens in the male fetal lung but that androgen synthesis must be a normal characteristic of mature PTII cells for both sexes. The production of androgens after the emergence of mature PTII cells should negatively regulate PTII cell maturation and thus, a novel and normal role for androgens in cell reprogramming is proposed.
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Regular paperDevelopment of fibroblast-type-II cell communications in fetal rabbit lung organ culture

Abstract

J. Biol. Chem.

Dev. Biol.

J. Biol. Chem.

Arch. Biochem. Biophys.

J. Biol. Chem.

J. Biol. Chem.

Dev. Biol.

Biochim. Biophys. Acta

Biochim. Biophys. Acta

Exp. Cell Res.

J. Steroid Biochem.

Am. J. of Physiol.

Regular paper
Development of fibroblast-type-II cell communications in fetal rabbit lung organ culture