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发育过程中接触天然和合成糖皮质激素的短期和长期影响。

Short- and long-term effects of exposure to natural and synthetic glucocorticoids during development.

机构信息

School of Biomedical Sciences, The University of Queensland, St Lucia, Qld., Australia.

出版信息

Clin Exp Pharmacol Physiol. 2012 Nov;39(11):979-89. doi: 10.1111/1440-1681.12009.

Abstract

1.Glucocorticoids (GCs) are necessary for fetal development, but clinical and experimental studies suggest that excess exposure may be detrimental to health in both the short and longer term. 2.Exposure of the fetus to synthetic GCs can occur if the mother has a medical condition requiring GC therapy (e.g. asthma) or if she threatens to deliver her baby prematurely. Synthetic GCs can readily cross the placenta and treatment is beneficial, at least in the short term, for maternal health and fetal survival. 3.Maternal stress during pregnancy can raise endogenous levels of the natural GC cortisol. A significant proportion of the cortisol is inactivated by the placental 'GC barrier'. However, exposure to severe stress during pregnancy can result in increased risk of miscarriage, low birth weight and behavioural deficits in children. 4.Animal studies have shown that excess exposure to both synthetic and natural GCs can alter normal organ development, including that of the heart, brain and kidney. The nature and severity of the organ impairment is dependent upon the timing of exposure and, in some cases, the type of GC used and the sex of the fetus. 5.In animal models, exposure to elevated GCs during pregnancy has been associated with adult-onset diseases, including elevated blood pressure, impaired cardiac and vascular function and altered metabolic function.

摘要
  1. 糖皮质激素(GCs)对于胎儿发育是必需的,但临床和实验研究表明,过多的暴露可能会对短期和长期的健康造成损害。

  2. 如果母亲患有需要 GC 治疗的疾病(例如哮喘),或者她有早产的危险,胎儿就会接触到合成的 GCs。合成的 GCs 可以很容易地穿过胎盘,并且治疗对母亲的健康和胎儿的生存至少在短期内是有益的。

  3. 孕妇在怀孕期间的压力会导致内源性天然 GC 皮质醇水平升高。胎盘“GC 屏障”会使很大一部分皮质醇失活。然而,怀孕期间严重的压力暴露会增加流产、低出生体重和儿童行为缺陷的风险。

  4. 动物研究表明,过多地暴露于合成和天然 GCs 都会改变正常的器官发育,包括心脏、大脑和肾脏。器官损伤的性质和严重程度取决于暴露的时间,在某些情况下,还取决于所使用的 GC 类型和胎儿的性别。

  5. 在动物模型中,怀孕期间暴露于升高的 GCs 与成年期疾病有关,包括血压升高、心脏和血管功能受损以及代谢功能改变。

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