Perinatal malnutrition programs sympathoadrenal and hypothalamic-pituitary-adrenal axis responsiveness to restraint stress in adult male rats
Perinatal malnutrition programs sympathoadrenal and hypothalamic-pituitary-adrenal axis responsiveness to restraint stress in adult male rats
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DOI：
10.1046/j.0007-1331.2001.00753.x
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发表时间：
2002-02-01
影响因子：
3.2
通讯作者：
Dupouy, JP
中科院分区：
文献类型：
--
作者：
Lesage, J;Dufourny, L;Dupouy, JP
在人类中，据报道，出生体重较低的成年男性皮质醇分泌控制发生了改变，这使得下丘脑-垂体-肾上腺（HPA）轴成为早期生命规划的可能主要目标。在大鼠中，我们最近发现，妊娠晚期母亲的食物限制会导致子宫内生长迟缓和胎儿过度暴露于母体皮质酮，从而扰乱后代 HPA 轴的发育。这项工作的首要目的是在成年雄性大鼠中调查围产期营养不良是否对基础条件和应激条件下的 HPA 轴活性产生长期影响。此外，由于 HPA 轴和交感神经系统都会被压力激活，因此这项工作的第二个目的是研究这些大鼠的基础和压力条件下的肾上腺髓质儿茶酚胺能系统。这项研究是在围产期营养不良的 4 个月大雄性大鼠和年龄匹配的对照动物上进行的。在基础条件下，围产期营养不良降低了体重和血浆皮质类固醇结合球蛋白（CBG）水平，但增加了CA1海马区盐皮质激素受体（MR）基因表达。束缚30分钟后，围产期营养不良（PM）大鼠的血浆去甲肾上腺素、促肾上腺皮质激素（ACTH）和皮质酮浓度与对照组相似，但计算得出的血浆游离皮质酮浓度显着高于对照组，而肾上腺素水平低于对照组。在恢复阶段，与对照组相比，PM 大鼠的血浆 ACTH 和皮质酮浓度迅速恢复至基线水平。这些数据表明，在 PM 大鼠中，皮质酮基础浓度升高，面对 CBG 降低和海马 MR 可能增加，导致皮质酮对靶细胞产生更大的影响，这些靶细胞介导 HPA 轴和交感肾上腺轴活动的负反馈机制。
In humans, an altered control of cortisol secretion was reported in adult men born with a low birth weight making the hypothalamic-pituitary-adrenal (HPA) axis a possible primary target of early life programming. In rats, we have recently shown that maternal food restriction during late pregnancy induces both an intrauterine growth retardation and an overexposure of fetuses to maternal corticosterone, which disturb the development of the HPA axis in offspring. The first aim of this work was to investigate, in adult male rats, whether perinatal malnutrition has long-lasting effects on the HPA axis activity during both basal and stressful conditions. Moreover, as the HPA axis arid sympathetic nervous system are both activated by stress, the second aim of this work was to investigate, in these rats, the adrenomedullary catecholaminergic system under basal and stressful conditions. This study was conducted on 4-month-old male rats malnourished during their perinatal life and on age-matched control animals. Under basal conditions, perinatal malnutrition reduced body weight and plasma corticosteroid-binding globulin (CBG) level but increased mineralocorticoid receptor (MR) gene expression in CA1 hippocampal area. After 30 min of restraint, perinatally malnourished (PM) rats showed increased plasma noradrenaline, adrenocorticotropin hormone (ACTH) and corticosterone concentrations similarly as controls, but calculated plasma-free corticosterone concentration was significantly higher, and adrenaline level lower than controls. During the phase of recovery, PM rats showed a rapid return of plasma ACTH and corticosterone concentrations to baseline levels in comparison with controls. These data suggest that in PM rats, an elevation of basal concentrations of corticosterone, in face of reduced CBG and probably increased hippocampal MR lead to a much larger impact of corticosterone on target cells that mediate the negative-feedback mechanism on the activities of both the HPA axis and sympathoadrenal one.