A sex difference in fetal lung development has long been recognized both clinically and experimentally. The mortality rate due to RDS is almost 2-fold higher in males than in females and the lungs of males are structurally not as well developed as those of females. We have found significantly less surfactant in human amniotic fluid from males than from females and less surfactant in lung lavage and amniotic fluid from male fetal rabbits than from females. The structural and functional development of the lung depends on mesenchymalparenchymal interactions. It has recently been found that one such interaction, type II cell synthesis of saturated phosphatidylcholine, is mediated by fibroblast prodcution of fibroblast pneumonocyte factor (FPF). Furthermore, the effects of glucocorticoids on lung structure and function are probably mediated by FPF, which is both anti-mitotic and stimulates surfactant synthesis. Our working hypothesis for the sex difference in fetal lung surfactant production is that there is cellular compartmentalization of the hormone-sensitive and SPC-synthetic mechanisms which reside in the mesenchyme and parenchyma, respectively. The (mesenchymal) fibroblast will process the steroid hormone, activating or inactivating it, resulting in stimulation or inhibition of FPF. The amount of FPF produced will determine the rate of SPC synthesis by the (parenchymal) type II alveolar cell. In the case of a putative androgen effect on surfactant metabolism we have formulated the following hypotheses: 1) androgens directly inhibit the synthesis of SPC by the fetal lung; 2) androgens block the producion of FPF by the fetal lung fibroblast; 3) the androgen inhibition of FPF is dependent on the metabolism of androgen by the fetal lung fibroblast. Prenatal treatment with glucocorticoids has significantly reduced the risk of RDS, albeit only 50% effective. Though the reasons for the failure of such treatment are unclear, it has recently been found that males are less responsive to this treatment than females. Elucidation of the mechanism(s) underlying the sex difference will yield more efficacious prophylaxis for RDS, and advance our understanding of regulation of fetal lung maturation.
NIH ExPorter
NIH ExPorter