Smith J, Fauquet M
J Neurosci. 1984 Aug;4(8):2160-72. doi: 10.1523/JNEUROSCI.04-08-02160.1984.
Glucocorticoid hormones stimulate catecholamine (CA) anabolism in a variety of adrenergic derivatives of the neural crest. We describe work performed to investigate the action of these steroids on the catecholaminergic differentiation of neural crest cells themselves. Crest was taken from the trunk level of 2-day quail embryos, before migration had begun, and was cultured in vitro. Adrenergic differentiation, characterized by the ability of the cultures to synthesize and store CA, was minimal and was not improved when glucocorticoids were added to the medium. In contrast, extensive adrenergic differentiation occurred when neural crest cells, removed from the embryo 24 hr later, toward the end of their migratory phase, were cultured with the sclerotomal component of the somite (their immediate embryonic microenvironment). This process was considerably stimulated by corticosteroids; the rate of conversion of [3H]tyrosine to intracellular CA (norepinephrine, epinephrine, and dopamine) was 2 to 3 times higher in cultures exposed for 7 days to 10(-6) to 10(-7) M hydrocortisone, corticosterone, or dexamethasone, and the diameter of the dense-core vesicles seen in cell bodies and processes after permanganate fixation was strikingly increased. The effect was specific for the adrenergic phenotype in that acetylcholine synthesis by the cultures was consistently unaffected by hormone treatment. We infer that glucocorticoids do not trigger adrenergic differentiation, but that they selectively enhance catecholaminergic properties in crest cells that have already been exposed to an appropriate signal of another kind. This conclusion is strengthened by the observation that glucocorticoids stimulated the development of CA-producing cells from premigratory crest grown in the presence of somites and notochord, postulated sources of factors initiating adrenergic differentiation in the embryo. Although the intervention of glucocorticoids in vivo at very early embryonic stages remains to be established, our results indicate that neural crest derivatives would be potentially responsive to these hormones as soon as the sympathetic ganglia form.
糖皮质激素可刺激神经嵴多种肾上腺素能衍生物中的儿茶酚胺（CA）合成代谢。我们描述了为研究这些类固醇对神经嵴细胞自身儿茶酚胺能分化的作用而开展的工作。在迁移开始前，从2日龄鹌鹑胚胎的躯干水平获取嵴，并进行体外培养。以培养物合成和储存CA的能力为特征的肾上腺素能分化程度很低，且向培养基中添加糖皮质激素后也未得到改善。相比之下，当在迁移阶段末期从胚胎中取出的神经嵴细胞与体节的硬骨成分（它们直接的胚胎微环境）一起培养时，会发生广泛的肾上腺素能分化。这个过程受到皮质类固醇的显著刺激；在暴露于10⁻⁶至10⁻⁷M氢化可的松、皮质酮或地塞米松7天的培养物中，[³H]酪氨酸转化为细胞内CA（去甲肾上腺素、肾上腺素和多巴胺）的速率高出2至3倍，并且在高锰酸盐固定后在细胞体和突起中看到的致密核心囊泡的直径显著增加。这种作用对肾上腺素能表型具有特异性，因为培养物中的乙酰胆碱合成始终不受激素处理的影响。我们推断，糖皮质激素不会触发肾上腺素能分化，而是选择性地增强已经暴露于另一种适当信号的嵴细胞中的儿茶酚胺能特性。在体节和脊索存在的情况下，从迁移前的嵴生长出的产生CA的细胞的发育受到糖皮质激素的刺激，这一观察结果强化了这一结论，体节和脊索被认为是胚胎中启动肾上腺素能分化的因子来源。尽管糖皮质激素在胚胎早期阶段在体内的干预作用仍有待确定，但我们的结果表明，一旦交感神经节形成，神经嵴衍生物可能会对这些激素产生反应。
