Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
Toxicol Lett. 2012 Nov 15;214(3):307-13. doi: 10.1016/j.toxlet.2012.09.001. Epub 2012 Sep 10.
Prenatal nicotine exposure inhibits the functional development of the hypothalamic-pituitary-adrenal (HPA) axis and alters glucose and lipid metabolism in intrauterine growth retardation (IUGR) fetal rats, but the postnatal consequence is unknown. We aimed to verify a neuroendocrine metabolic programmed alteration in IUGR offspring whose mothers were subcutaneously treated with 2mg/kgd of nicotine from gestational day 11 to 20. In the nicotine group, blood adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels were higher before postnatal day 35 and then returned to lower than the respective control. The adult offspring showed unchanged blood glucose but increased blood total cholesterol (TCH) and triglyceride (TG) levels. However, after chronic stress, the mRNA expression levels of hippocampal glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) were lower, but gain rates of ACTH and CORT levels were greater compared to the control. Additionally, the level of blood glucose was increased, while the elevated levels of blood TCH and TG before stress were close to the control levels. These results suggested that prenatal nicotine exposure induced an HPA axis-associated neuroendocrine metabolic programmed alteration in adult offspring, which might be attributed to hippocampal functional injury in utero.
产前尼古丁暴露会抑制下丘脑-垂体-肾上腺（HPA）轴的功能发育，并改变宫内发育迟缓（IUGR）胎儿的葡萄糖和脂质代谢，但产后的后果尚不清楚。我们旨在验证接受皮下注射 2mg/kg/d 尼古丁治疗的 IUGR 后代是否存在神经内分泌代谢程序化改变，从妊娠第 11 天到第 20 天。在尼古丁组中，出生后第 35 天之前，血液促肾上腺皮质激素（ACTH）和皮质酮（CORT）水平升高，然后降至低于各自的对照组。成年后代的血糖水平不变，但总胆固醇（TCH）和甘油三酯（TG）水平升高。然而，在慢性应激后，海马糖皮质激素受体（GR）和盐皮质激素受体（MR）的 mRNA 表达水平较低，但 ACTH 和 CORT 水平的升高幅度大于对照组。此外，血糖水平升高，而应激前升高的 TCH 和 TG 水平接近对照组水平。这些结果表明，产前尼古丁暴露会导致成年后代 HPA 轴相关的神经内分泌代谢程序化改变，这可能归因于宫内海马功能损伤。
