Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, United States.
Front Neuroendocrinol. 2013 Jan;34(1):27-46. doi: 10.1016/j.yfrne.2012.11.002. Epub 2012 Nov 27.
Adverse environments during the fetal and neonatal development period may permanently program physiology and metabolism, and lead to increased risk of diseases in later life. Programming of the hypothalamic-pituitary-adrenal (HPA) axis is one of the key mechanisms that contribute to altered metabolism and response to stress. Programming of the HPA axis often involves epigenetic modification of the glucocorticoid receptor (GR) gene promoter, which influences tissue-specific GR expression patterns and response to stimuli. This review summarizes the current state of research on the HPA axis and programming of health and disease in the adult, focusing on the epigenetic regulation of GR gene expression patterns in response to fetal and neonatal stress. Aberrant GR gene expression patterns in the developing brain may have a significant negative impact on protection of the immature brain against hypoxic-ischemic encephalopathy in the critical period of development during and immediately after birth.
胎儿和新生儿发育期间的不良环境可能会永久性地调节生理和代谢，并导致以后生活中疾病的风险增加。下丘脑-垂体-肾上腺 (HPA) 轴的编程是导致代谢改变和应激反应的关键机制之一。HPA 轴的编程通常涉及糖皮质激素受体 (GR) 基因启动子的表观遗传修饰，这会影响组织特异性 GR 表达模式和对刺激的反应。本综述总结了目前关于 HPA 轴和成年期健康和疾病编程的研究状况，重点介绍了胎儿和新生儿应激对 GR 基因表达模式的表观遗传调控。发育中大脑中异常的 GR 基因表达模式可能会对出生期间和之后的关键发育时期保护未成熟大脑免受缺氧缺血性脑病产生重大负面影响。
