CORTICOTROPIN-RELEASING HORMONE DEFICIENCY REVEALS MAJOR FETAL BUT NOT ADULT GLUCOCORTICOID NEED
CORTICOTROPIN-RELEASING HORMONE DEFICIENCY REVEALS MAJOR FETAL BUT NOT ADULT GLUCOCORTICOID NEED
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DOI：
10.1038/373427a0
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发表时间：
1995-02-02
期刊：
影响因子：
64.8
通讯作者：
MAJZOUB, JA
中科院分区：
文献类型：
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作者：
MUGLIA, L;JACOBSON, L;MAJZOUB, JA
机体通过激活下丘脑-垂体-肾上腺（HPA）轴和释放糖皮质激素对应激作出反应。成人糖皮质激素的产生调节碳水化合物和氨基酸代谢，维持血压，并抑制炎症反应（1）。在胎儿中，外源性糖皮质激素加速肺（2）和胃肠道酶系统（3）的成熟，并促进肝糖原沉积（4）。促肾上腺皮质激素释放激素（CRH）是一种由41个氨基酸组成的神经肽，产生于下丘脑室旁核和大脑皮层的许多区域（5，6），与HPA轴（7）和对压力的行为反应（8）有关。为了确定CRH在HPA轴对应激和胎儿发育的反应中的重要性，我们通过胚胎干（ES）细胞中的靶向突变构建了CRH缺陷的哺乳动物模型（9）。我们在这里报告，促肾上腺皮质激素释放激素缺乏的小鼠揭示了胎儿肺成熟的糖皮质激素的要求。出生后，尽管明显的糖皮质激素缺乏，这些小鼠表现出正常的生长，生育力和寿命，这表明糖皮质激素的主要作用是在胎儿，而不是出生后的生活。
The body responds to stress by activation of the hypothalamic-pituitary-adrenal (HPA) axis and release of glucocorticoids. Glucocorticoid production in the adult regulates carbohydrate and amino-acid metabolism, maintains blood pressure, and restrains the inflammatory response(1). In the fetus, exogenous glucocorticoids accelerate maturation of lung(2) and gastrointestinal enzyme systems(3) and promote hepatic glycogen deposition(4). Corticotropin-releasing hormone (CRH), a 41-amino-acid neuropeptide produced in the paraventricular nucleus of the hypothalamus and many regions of the cerebral cortex(5,6), has been implicated in both the HPA axis(7) and behavioural responses(8) to stress. To define the importance of CRH in the response of the HPA axis to stress and fetal development, we have constructed a mammalian model of CRH deficiency by targeted mutation in embryonic stem (ES) cells(9). We report here that corticotropin-releasing hormone-deficient mice reveal a fetal glucocorticoid requirement for lung maturation. Postnatally, despite marked glucocorticoid deficiency, these mice exhibit normal growth, fertility and longevity, suggesting that the major role of glucocorticoid is during fetal rather than postnatal life.