A hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion.
A hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion.
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DOI：
10.1016/j.taap.2012.08.016
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发表时间：
2012-11
影响因子：
3.8
通讯作者：
Dan Xu;Yimeng Wu;Fulin Liu;Yanzhuo Liu;L. Shen;You-ying Lei;J. Liu;Jie Ping;Jun Qin
中科院分区：
文献类型：
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作者：
Dan Xu;Yimeng Wu;Fulin Liu;Yanzhuo Liu;L. Shen;You-ying Lei;J. Liu;Jie Ping;Jun Qin
咖啡因是胎儿宫内发育迟缓（IUGR）的一个确定因素。先前，我们已经证实，产前摄入咖啡因抑制下丘脑-垂体-肾上腺（HPA）轴的发展，并改变IUGR胎鼠的糖和脂质代谢。在这项研究中，我们的目的是验证产前摄入咖啡因的后代大鼠神经内分泌代谢的程序性改变。结果表明，产前摄入咖啡因（120 mg/www.example.com）可导致仔鼠体重下降和IUGR发生率升高;咖啡因组仔鼠血促肾上腺皮质激素（ACTH）和皮质酮浓度在生后早期显著升高，后期下降;成年后血糖水平无变化，血总胆固醇（TCH）和甘油三酯（TG）显著升高。慢性应激后，咖啡因组大鼠血ACTH、皮质酮浓度及增重率明显升高，血糖升高，TCH、TG降低。此外，咖啡因组海马盐皮质激素受体（MR）的表达最初降低，随后出生后增加。慢性应激后11 β-羟类固醇脱氢酶-1、糖皮质激素受体（GR）、MR及MR/GR比值均显著降低。提示产前摄入咖啡因可导致IUGR仔鼠HPA轴功能紊乱及相关的神经内分泌代谢程序性改变，其机制可能与海马功能损伤有关。这些观察结果为解释IUGR后代对代谢综合征及相关疾病的易感性提供了有价值的实验依据。
Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic–pituitary–adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases.