McMillan E M, King G M, Adamson I Y
Department of Pathology, University of Manitoba, Winnipeg, Canada.
Exp Lung Res. 1989 Mar;15(2):167-79. doi: 10.3109/01902148909087851.
Sex-related differences may be present during fetal lung growth and at the onset of surfactant synthesis. In this study we investigated the role of dihydrotestosterone (DHT) and estrogen (EST) on cell division and on labeled palmitate incorporation into disaturated phosphatidylcholine (DSPC) at various times of gestation. Using organ cultures of fetal rat lung from sexed littermates, it was shown that both DHT and EST reduce DNA synthesis only in tissue taken during the rapid growth phase from day 16 to 19 of gestation. From autoradiographic counts, epithelial cell division was most affected. Both hormones reduced DSPC synthesis in explants prepared at day 18, when levels are normally low. At day 19, DHT reduced palmitate incorporation into DSPC of female explants to the male level; subsequently DHT had no effect on any tissue. In contrast, the addition of EST stimulated DSPC synthesis 40% above controls in both male and female explants taken at day 20 only. The results suggest that sex differences seen in late fetal lung development may arise from the combined effects of slowed epithelial growth induced by these hormones followed by inhibition of DSPC synthesis by DHT and acceleration by EST at the crucial period when surfactant synthesis begins.
在胎儿肺生长期间和表面活性剂合成开始时可能存在性别差异。在本研究中,我们研究了双氢睾酮(DHT)和雌激素(EST)在妊娠不同时期对细胞分裂以及标记的棕榈酸掺入二饱和磷脂酰胆碱(DSPC)的作用。使用来自同性别同窝幼崽的胎鼠肺器官培养物,结果表明,仅在妊娠第16至19天快速生长阶段获取的组织中,DHT和EST均会减少DNA合成。从放射自显影计数来看,上皮细胞分裂受影响最大。在第18天制备的外植体中,两种激素均会减少DSPC合成,此时其水平通常较低。在第19天,DHT将雌性外植体中棕榈酸掺入DSPC的水平降至雄性水平;随后DHT对任何组织均无影响。相比之下,仅在第20天获取的雄性和雌性外植体中添加EST会使DSPC合成比对照增加40%。结果表明,胎儿肺发育后期出现的性别差异可能源于这些激素诱导的上皮生长减缓的综合作用,随后在表面活性剂合成开始的关键时期,DHT抑制DSPC合成,而EST促进其合成。