Maternal dexamethasone treatment in late gestation alters glucocorticoid and mineralocorticoid receptor mRNA in the fetal guinea pig brain
Maternal dexamethasone treatment in late gestation alters glucocorticoid and mineralocorticoid receptor mRNA in the fetal guinea pig brain
复制标题
DOI：
10.1016/s0006-8993(99)02064-8
复制
发表时间：
1999-11-06
期刊：
影响因子：
2.9
通讯作者：
Matthews, SG
中科院分区：
文献类型：
--
作者：
Dean, F;Matthews, SG
胎儿下丘脑-垂体-肾上腺皮质（HPA）轴的发育对胎儿的成熟和应激反应至关重要。与大鼠不同，豚鼠产下成熟的幼崽，大脑生长的高峰出现在妊娠的48 - 52天（75%）。在豚鼠脑快速生长时，糖皮质激素受体（GR）和盐皮质激素受体（MR）系统广泛发育。由于约10%的孕妇在妊娠晚期接受合成糖皮质激素治疗，以促进胎儿器官成熟，我们测试了胎儿暴露于糖皮质激素改变脑中发育中的GR和MR系统的假设。在妊娠第50天和第51天（期限= 70天），对妊娠豚鼠皮下注射地塞米松（dex; 1 mg/kg）或溶剂。在第52天，处死豚鼠，迅速取出胎仔。母体dex处理导致雌性胎仔血浆皮质醇浓度升高，但雄性胎仔血浆皮质醇浓度降低。母体dex治疗后，雌性和雄性胎儿的血浆甲状腺素水平均升高。地塞米松暴露导致海马CA1 - 2区MR和GR mRNA显著增加，雌性胎儿齿状回MR mRNA显著增加。地塞米松对雄胎GR和MR mRNA无影响。总之，合成糖皮质激素对发育中的大脑GR和MR系统的影响是性别特异性的，并且仅限于海马的非常特定的区域。由于海马在调节HPA功能的糖皮质激素负反馈中起着重要作用，因此胎儿皮质类固醇受体发育的改变可能形成胎儿暴露于内源性或合成糖皮质激素后HPA活性永久改变的基础。(C)1999年由Elsevier Science B.V.出版，版权所有。
Development of the fetal hypothalamo-pituitary-adrenocortical (HPA) axis is critical for fetal maturation and responses to stress. Guinea pigs, unlike rats, give birth to mature young, and peak brain growth occurs around days 48-52 (75%) of gestation. There is extensive development of the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) systems at the time of rapid brain growth in guinea pigs, Since approximately 10% of pregnant women are treated with synthetic glucocorticoids in late gestation, to promote fetal organ maturation, we tested the hypothesis that fetal exposure to glucocorticoids modifies developing GR and MR systems in the brain. Pregnant-guinea pigs were subcutaneously injected with dexamethasone (dex; 1 mg/kg) or vehicle on days 50 and 51 of gestation (term = 70 days). On day 52, guinea pigs were killed and the fetuses rapidly, removed, Maternal dex treatment resulted in increased plasma cortisol concentrations in female fetuses, but decreased cortisol in male fetuses. Plasma thyroxine levels were increased in both female and male fetuses following maternal dex-treatment. Exposure to dex resulted in significant increases in MR and GR mRNA in the CA1-2 region of the hippocampus, and MR mRNA in the dentate gyrus in female fetuses. There was no effect of dex on GR or MR mRNA in the male fetuses. In conclusion, the effect of synthetic glucocorticoid on the developing brain GR and MR systems is sex-specific and is confined to very specific regions of the hippocampus. Since the hippocampus plays a central role in mediating glucocorticoid negative feedback of HPA function, alterations in the fetal development of corticosteroid receptors may form the basis of permanently modified HPA activity following fetal exposure to endogenous or synthetic glucocorticoid. (C) 1999 Published by Elsevier Science B.V. All rights reserved.