Rat fetal lung is a target tissue for 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25 (OH)2 D3]. We have identified the cells that respond to the hormone and tested the hypothesis that the lung is also a source of 1 alpha,25(OH)2D3. We found that 1) at the end of pregnancy (days 20-21) alveolar type II cells (ATII) bore 1 alpha,25(OH)2D3 receptors and responded to the hormone. Incubating these cells with 10(-9) M 1 alpha,25(OH)2D3 for 48 h stimulated the synthesis (87.3 +/- 9.1%) and release (61.7 +/- 6.1%) of disaturated phosphatidylcholine; 2) EB-1213, a 1 alpha,25(OH)2D3 analogue with low calcemic activity, had similar effects on ATII; 3) neither fetal lung fibroblasts nor neonatal ATII (day 2 postpartum) expressed 1 alpha,25(OH)2D3 receptors; and 4) in contrast, fetal lung fibroblasts taken on days 19-22 of gestation converted [3H]25(OH)D3 to [3H]1 alpha,25(OH)2D3, whereas ATII and skin fibroblasts did not. These findings suggest that 1 alpha,25(OH)2D3 is a local mediator of epithelial-mesenchymal cell interactions in the developing rat lung and that 1 alpha,25(OH)2D3 or EB-1213 might be therapeutically useful in treating the respiratory distress syndrome of premature neonates.

Lung tissue from 18-day-old rat fetuses was cultured in the presence of 1,25-dihydroxyvitamin D₃ – 1,25(OH)₂D₃ –– (10^––9M) and dexamethasone (10^––7M) for 48 h. 1,25(OH)₂D₃ increased the lung content in phospholipids more specifically related to lung surfactant, phosphatidylcholine and phosphatidylglycerol. This increase was similar to that observed with dexamethasone. In addition, unlike dexamethasone, 1,25(OH)₂D₃ stimulated the surfactant release into luminal spaces, as evidenced by light and electron microscopy. Thus, vitamin D₃ might represent an additional factor controlling fetal lung maturation by stimulating phospholipid synthesis and surfactant release from type II cells.

Specific binding sites for 1 alpha,25 dihydroxyvitamin D3 [1 alpha,25-(OH)2D3] localized to type II pneumocytes have been evidenced in fetal rat lung at the end of gestation, suggesting a role for vitamin D3 in the control of lung maturation. In this study, we describe the morphological changes that occur in lung explants from 18-day-old rat fetuses grown for 1 and 2 days in control conditions and in the presence of 1 alpha,25(OH)2D3 (10(-9) M) or dexamethasone (10(-7) M). Point counting and planimetric measurements on light and electron micrographs show that 1 alpha,25-(OH)2D3 1) dramatically decreases the mean glycogen content of type II cell profiles between days 1 and 2 of the culture, suggesting an acceleration of the glycogenolytic processes normally occurring at that stage and 2) does not change the intracellular osmiophilic lamellar body (OLB) content of cell profiles, but increases the amount of intraluminal surfactant by 126% when expressed as surfactant clusters surface area/section surface area and by 129% when expressed on a per cell basis, suggesting a stimulation of surfactant synthesis and secretion. By contrast, dexamethasone increases the mean intracellular OLB content of type II cell profiles by 306% and decreases the relative surface area of secreted material by 53 and 73%. In conclusion, 1 alpha,25(OH)2D3 accelerates the physiological maturation of fetal rat type II pneumocytes and could represent a key factor for the onset of normal lung function at birth.

Diacylglycerol (DG) and triacylglycerol (TG) levels in rat lung tissue were determined from day 17 of gestation to day 10 post partum and studied in parallel with ultrastructural differentiation. The DG level, although rather low at all measured stages, rose significantly between days 17 and 19 and at birth. TG level increased steadily during the whole studied period and especially between days 17 and 19 and at birth. In DG as well as in TG, saturated fatty acids were predominant. The rising of TG levels paralleled the appearance and accumulation of lipid vacuoles in mesodermal cells lying in contact with type II cells. The possible role of these cells is discussed.