Fetal programming of hypothalamo-pituitary-adrenal function: prenatal stress and glucocorticoids

Fetal programming of hypothalamo-pituitary-adrenal function: prenatal stress and glucocorticoids
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DOI:
10.1113/jphysiol.2006.105254
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发表时间:
2006-04-01
影响因子:
5.5
通讯作者:
Matthews, SG
Matthews, SG
中科院分区:
医学1区
文献类型:
--
作者:
Kapoor, A;Dunn, E;Matthews, SG

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产前应激(PS)和母亲暴露于外源性糖皮质激素可导致下丘脑-垂体-肾上腺(HPA)功能和应激相关行为的永久性改变。这两种操作都会增加胎儿对糖皮质激素的暴露。糖皮质激素对正常大脑发育的许多方面都是必不可少的,但胎儿大脑暴露在过量的糖皮质激素下可能会对神经内分泌功能产生终生影响。内源性糖皮质激素和合成糖皮质激素对胎儿大脑都有许多快速影响,包括神经递质系统和转录机制的改变。这种胎儿暴露以一种性别依赖的方式永久性地改变了青春期前、青春期后和衰老后代的HPA功能。产前应激和外源性糖皮质激素操作也会导致行为、大脑和器官形态的改变,以及其他内分泌系统调节的改变。暴露于PS或合成糖皮质激素的时机对表型结局的性质有巨大影响,这一点也越来越明显。内分泌功能的永久性变化最终将对人类和动物种群的健康产生影响。
Prenatal stress (PS) and maternal exposure to exogenous glucocorticoids can lead to permanent modification of hypothalamo-pituitary-adrenal (HPA) function and stress-related behaviour. Both of these manipulations lead to increased fetal exposure to glucocorticoids. Glucocorticoids are essential for many aspects of normal brain development, but exposure of the fetal brain to an excess of glucocorticoids can have life-long effects on neuroendocrine function. Both endogenous glucocorticoid and synthetic glucocorticoid exposure have a number of rapid effects in the fetal brain, including modification of neurotransmitter systems and transcriptional machinery. Such fetal exposure permanently alters HPA function in prepubertal, postpubertal and ageing offspring, in a sex-dependent manner. Prenatal stress and exogenous glucocorticoid manipulation also lead to the modification of behaviour, brain and organ morphology, as well as altered regulation of other endocrine systems. It is also becoming increasingly apparent that the timing of exposure to PS or synthetic glucocorticoids has tremendous effects on the nature of the phenotypic outcome. Permanent changes in endocrine function will ultimately impact on health in both human and animal populations.