Identification of sex-specific differences in surfactant synthesis in rat lung
Identification of sex-specific differences in surfactant synthesis in rat lung
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DOI：
10.1203/00006450-199912000-00014
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发表时间：
1999-12-01
影响因子：
3.6
通讯作者：
Mallampalli, RK
中科院分区：
文献类型：
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作者：
McCoy, DM;Salome, RG;Mallampalli, RK
与几个物种的雌性胎儿相比，先前已在雄性胎儿中发现肺成熟延迟和表面活性剂磷脂酰胆碱水平较低。我们研究了表面活性剂含量的性别差异的机制，通过检查参数的磷脂酰胆碱营业额和生物合成，后者进行了评估，通过测量代谢步骤内的生物合成途径。与男性肺细胞相比，从女性胎儿新鲜分离的肺细胞含有较高水平的二饱和磷脂酰胆碱，表面活性剂脂质的标志物。女性混合单层文化表现出71%的增加胆碱掺入二饱和磷脂酰胆碱与男性文化相比。男性文化表现出显着更大的释放[H-3]-花生四烯酸到介质中相比，女性，这表明性别差异磷脂酶活性。然而，脉冲追踪研究表明，在二饱和磷脂酰胆碱的降解方面没有性别差异，这一点通过磷脂酶A、磷脂酰胆碱特异性磷脂酶C和磷脂酶D的测定得到证实。女性混合肺细胞，然而，有更大的细胞胆碱运输和活性的胞苷酰转移酶，磷脂酰胆碱合成的速率调节酶。单独的研究表明，暴露于皮质醇刺激的成纤维细胞条件培养基加转化生长因子-β-中和抗体的性别特异性前II型细胞培养物刺激胞苷酰转移酶活性在更大程度上在男性细胞与女性细胞相比。这些研究表明，表面活性剂磷脂含量的性别差异不是由于磷脂周转率的差异，而是表面活性剂生物合成途径中特定代谢步骤的差异调节。这些数据还支持转化生长因子-p作为男性肺内关键表面活性剂生物合成酶的负调节剂的作用。
Delayed lung maturation and lower levels of surfactant phosphatidylcholine have been previously identified in male fetuses compared with female fetuses in several species. We investigated the mechanisms for sex differences in surfactant content by examining parameters of phosphatidylchorine turnover and biosynthesis; the latter was evaluated by measuring metabolic steps within the biosynthetic pathway. Compared with male lung cells, freshly isolated lung cells from female fetuses contained higher levels of disaturated phosphatidylcholine, a marker of surfactant lipid. Female mixed monolayer cultures exhibited a 71% increase in choline incorporation into disaturated phosphatidyicholine compared with male cultures. Male cultures exhibited significantly greater release of [H-3]-arachidonic acid into the medium compared with females, suggesting sex differences in phospholipase activity. However, pulse-chase studies showed no sex differences in degradation of disaturated phosphatidylcholine, which was confirmed by assays of phospholipase A,, phosphatidylcholine-specific phospholipase C, and phospholipase D. Female mixed lung cells, however, had greater rates of cellular choline transport and activity of cytidylyltransferase, the rate-regulatory enzyme for phosphatidylcholine synthesis. Separate studies showed that exposure of sex-specific pretype II cell cultures to cortisol-stimulated fibroblast-conditioned medium plus transforming growth factor-beta-neutralizing antibody stimulated cytidylyltransferase activity to a greater extent in male cells compared with female cells. These studies indicate that sex differences in surfactant phospholipid content are not due to differences in phospholipid turnover, but rather differential regulation of specific metabolic steps within the surfactant biosynthetic pathway. The data also support a role for transforming growth factor-p as a negative regulator of a key surfactant biosynthetic enzyme within male lungs.