Intrauterine events and the programming of adulthood disease: the role of fetal glucocorticoid exposure (Review).
Intrauterine events and the programming of adulthood disease: the role of fetal glucocorticoid exposure (Review).
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DOI：
10.3892/ijmm.2.5.607
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发表时间：
1998-11
影响因子：
5.4
通讯作者：
M. Nyirenda;J. Seckl
中科院分区：
文献类型：
--
作者：
M. Nyirenda;J. Seckl
越来越多的人类流行病学证据表明，低出生体重与后来的心血管和代谢疾病有关，包括高血压、胰岛素抵抗、高血压和缺血性心脏病死亡。这种联系的分子机制尚不清楚，但胎儿糖皮质激素暴露可能起作用。在成年哺乳动物中，糖皮质激素参与控制维持稳态的几种生理过程，包括协调对应激的反应。在发育过程中，糖皮质激素具有重要的调节功能，使生物体为宫外生活所必需的代谢适应做好准备。胎儿糖皮质激素负荷部分受胎盘和胎儿11 β-羟基类固醇脱氢酶2型（11 β-HSD 2）调节，该酶催化母体和胎儿糖皮质激素快速分解为惰性产物。超生理剂量的糖皮质激素延缓胎儿生长，人类宫内发育迟缓与皮质醇水平升高有关。最近的研究表明，大鼠在子宫内暴露于过量的糖皮质激素会降低出生体重，并导致成年后代的永久性高血压和高血压。这些观察结果表明，糖皮质激素可能是低出生体重和后期疾病之间的联系。了解产前糖皮质激素作用的分子细节可能为常见心血管和代谢疾病的发病机制提供新的见解。
There is increasing epidemiological evidence in humans which associates low birth weight with later cardiovascular and metabolic disorders including hypertension, insulin resistance, hyperlipidaemia and death from ischaemic heart disease. The molecular mechanisms underlying this link are unknown but fetal glucocorticoid exposure may play a role. In adult mammals, glucocorticoid hormones are involved in control of several physiological processes that maintain homeostasis including coordination of responses to stress. During development, glucocorticoids have important regulatory functions to prepare the organism for metabolic adaptations necessary for extrauterine life. Fetal glucocorticoid load is, in part, regulated by placental and fetal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) which catalyses a rapid breakdown of maternal and fetal glucocorticoids into inert products. Supraphysiological doses of glucocorticoids retard fetal growth, and human intrauterine growth retardation is associated with elevated cortisol levels. Recent studies have shown that exposing rats to excessive glucocorticoids in utero reduces birth weight and causes permanent hypertension and hyperglycaemia in the adult offspring. These observations show that glucocorticoids could be the link between low birth weight and later disease. Understanding of the molecular details involved in prenatal glucocorticoid action may provide novel insights into the pathogenesis of common cardiovascular and metabolic disorders.