Fetal lung in organ culture. IV. Supra-additive hormone interactions.
Fetal lung in organ culture. IV. Supra-additive hormone interactions.
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器官培养中的胎儿肺。
DOI：
10.1152/jappl.1982.52.6.1420
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
Wilson,CM
中科院分区：
文献类型：
--
作者：
Gross,I;Wilson,CM
皮质类固醇、甲状腺激素和茶碱此前已被证明可以加速胎儿肺的成熟。我们在器官培养中研究了这些药物之间的相互作用与18d胎鼠肺外植体磷脂合成的关系。当地塞米松浓度为100 nM时，对磷脂酰胆碱--肺表面活性物质中最丰富的磷脂-胆碱的掺入速率有最大的刺激作用。100 nM地塞米松、1.0 mM茶碱或两者联合作用48h后，胆碱掺入饱和磷脂酰胆碱的速率分别增加144、157和508%。地塞米松与二丁基腺苷3‘，5’-环磷酸(CAMP)之间存在相似的超相加作用，但与咖啡因的作用不那么显著。前体掺入速率的提高与培养物中不饱和卵磷脂含量的显著增加有关。地塞米松与100 nM三碘甲腺原氨酸(产生最大效应的浓度)联合使用也可产生超加性刺激，但程度较小。这些体外相互作用的发现表明，这些药物在不同的生化位置作用于肺，但它们在细胞水平上相互作用的机制尚未建立。这些数据为体内动物研究联合应用激素对胎儿肺成熟的影响提供了理论基础。
Corticosteroids, thyroid hormones, and theophylline have previously been shown to accelerate fetal lung maturation. We have examined the interactions between these agents in relation to phospholipid synthesis in explants of 18-day fetal rat lung in organ culture. Maximal stimulation of the rate of incorporation of choline into phosphatidylcholine, the most abundant phospholipid in pulmonary surfactant, was observed at a dexamethasone concentration of 100 nM. Exposure to 100 nM dexamethasone, 1.0 mM theophylline, or a combination of the two agents for 48 h resulted, respectively, in 144, 157, and 508% stimulation of the rate of incorporation of choline into disaturated phosphatidylcholine. Similar supra-additive interactions between dexamethasone and dibutyryl adenosine 3′,5′-cyclic monophosphate (cAMP) were observed, but the effects with caffeine were less striking. The increase in the rate of precursor incorporation was associated with a significant increase in the disaturated phosphatidylcholine content of the cultures. Combination of dexamethasone with 100 nM triiodothyronine (the concn producing maximal effects) also resulted in supra-additive stimulation but to a smaller degree. These findings of interactions in vitro suggest that the agents act on the lung at different biochemical sites, but the mechanisms whereby they interact at the cellular level have yet to be established. The data provide a rationale for in vivo animal studies of the effects of combined hormone administration on fetal lung maturation.