Douglas A J, Meddle S L, Toschi N, Bosch O J, Neumann I D
Laboratory of Neuroendocrinology, Centre for Integrative Physiology, School of Biomedical and Clinical Laboratory Sciences, University of Edinburgh, Edinburgh, UK.
J Neuroendocrinol. 2005 Jan;17(1):40-8. doi: 10.1111/j.1365-2826.2005.01272.x.
We investigated whether changes in noradrenaline neurotransmission in the hypothalamus could explain the hyporesponsiveness of the hypothalamic-pituitary-adrenal (HPA) axis in late pregnancy. Noradrenaline release within the hypothalamic paraventricular nucleus in response to swim stress, as estimated by microdialysis and high-performance liquid chromatography, was lower in 20-day pregnant rats compared to virgin rats. Driving a central noradrenergic pathway using intravenous cholecystokinin increased adrenocorticotropic hormone (ACTH) secretion in virgin rats, but the response was significantly less in 16-day and 20-day pregnant rats. Thus, the activity of noradrenergic inputs to the paraventricular nucleus and the HPA axis is attenuated in late pregnancy. The sensitivity of the HPA axis to noradrenaline in pregnancy was investigated by intracerebroventricular administration of an alpha1-receptor antagonist, benoxathian, before and during exposure to swim stress. In virgin rats, benoxathian increased basal and stress-induced ACTH secretion, but in late pregnant rats the benoxathian effects were attenuated, indicating reduced sensitivity of the HPA axis to noradrenaline neurotransmission and/or the inability of the system to become disinhibited at this time. alpha1A-adrenoreceptor mRNA expression in the parvocellular and magnocellular paraventricular nucleus, measured by in situ hybridisation, was decreased in late pregnant compared to virgin rats. Additionally, blocking endogenous opioid inhibition with naloxone pretreatment restored the ACTH secretory response to cholecystokinin in pregnant rats. Thus, in late pregnancy, there is reduced noradrenergic input to the paraventricular nucleus and reduced alpha1A-receptor expression in the paraventricular nucleus, both of which may contribute to the reduced responsiveness of the HPA axis in pregnancy.
我们研究了下丘脑去甲肾上腺素神经传递的变化是否能解释妊娠晚期下丘脑 - 垂体 - 肾上腺（HPA）轴反应性降低的现象。通过微透析和高效液相色谱法估算，20日龄妊娠大鼠下丘脑室旁核内对游泳应激的去甲肾上腺素释放量低于未孕大鼠。静脉注射胆囊收缩素驱动中枢去甲肾上腺素能通路可增加未孕大鼠促肾上腺皮质激素（ACTH）的分泌，但在16日龄和20日龄妊娠大鼠中，这种反应明显减弱。因此，妊娠晚期室旁核和HPA轴的去甲肾上腺素能输入活动减弱。通过在暴露于游泳应激之前和期间脑室内注射α1受体拮抗剂贝诺沙噻，研究了妊娠期间HPA轴对去甲肾上腺素的敏感性。在未孕大鼠中，贝诺沙噻增加了基础和应激诱导的ACTH分泌，但在妊娠晚期大鼠中，贝诺沙噻的作用减弱，表明HPA轴对去甲肾上腺素神经传递的敏感性降低和/或此时该系统无法解除抑制。通过原位杂交测量，与未孕大鼠相比，妊娠晚期室旁核小细胞和大细胞中α1A - 肾上腺素能受体mRNA表达降低。此外，用纳洛酮预处理阻断内源性阿片类物质抑制可恢复妊娠大鼠对胆囊收缩素的ACTH分泌反应。因此，在妊娠晚期，室旁核的去甲肾上腺素能输入减少，室旁核中α1A受体表达降低，这两者都可能导致妊娠期间HPA轴反应性降低。
