Brunton Paula J, Bales Juliana, Russell John A
Laboratory of Neuroendocrinology, Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, Scotland, United Kingdom.
Endocrinology. 2006 Aug;147(8):3737-45. doi: 10.1210/en.2006-0048. Epub 2006 May 4.
Metabolic peptides such as orexin and neuropeptide Y (NPY) exert profound effects on feeding but also act centrally to stimulate the hypothalamo-pituitary-adrenal (HPA) axis. In late pregnancy the HPA axis is hyporesponsive to centrally administered orexin-A, which signals to the HPA axis, in part, via arcuate NPY neurones. We investigated whether reduced HPA axis responses to orexin may be a consequence of down-regulated NPY signaling to the paraventricular nucleus (PVN) in pregnancy. Pregnant (d 21) and virgin rats were blood sampled for ACTH, corticosterone, and oxytocin (also a stress hormone in rats) before and after intracerebroventricular NPY or vehicle. Behavior was monitored. Rats were killed 4 h after NPY and brains removed for in situ hybridization. In another experiment rats were given vehicle or NPY, perfuse fixed 90 min later, and brain sections processed for Fos and oxytocin immunocytochemistry. NPY significantly increased ACTH, corticosterone and oxytocin secretion in the virgins but had no such effect on ACTH or oxytocin in the pregnant rats; the corticosterone response to NPY was markedly attenuated in pregnant rats. NPY increased CRH and vasopressin mRNA expression in the parvocellular PVN and stimulated Fos expression in magnocellular supraoptic and PVN oxytocin neurones of virgin but not pregnant rats. NPY increased food intake and drinking similarly in virgin and pregnant rats. Thus, neuroendocrine stress responses to central NPY are absent in late pregnancy, whereas ingestive behavioral responses are intact. These changes may explain the similarly attenuated HPA response to centrally administered orexin-A and will favor anabolic adaptations in pregnancy.
诸如食欲肽和神经肽Y（NPY）等代谢肽不仅对进食有深远影响，还在中枢发挥作用，刺激下丘脑-垂体-肾上腺（HPA）轴。在妊娠晚期，HPA轴对中枢给予的食欲肽A反应低下，食欲肽A部分通过弓状核NPY神经元向HPA轴发出信号。我们研究了妊娠期间HPA轴对食欲肽反应降低是否可能是由于向室旁核（PVN）的NPY信号下调所致。对妊娠（第21天）大鼠和未孕大鼠在脑室内注射NPY或溶剂前后采集血液样本，检测促肾上腺皮质激素（ACTH）、皮质酮和催产素（大鼠体内也是一种应激激素）水平。监测大鼠行为。注射NPY 4小时后处死大鼠，取出大脑进行原位杂交。在另一项实验中，给大鼠注射溶剂或NPY，90分钟后进行灌注固定，对脑切片进行Fos和催产素免疫细胞化学处理。NPY显著增加未孕大鼠的ACTH、皮质酮和催产素分泌，但对妊娠大鼠的ACTH或催产素无此作用；妊娠大鼠对NPY的皮质酮反应明显减弱。NPY增加了小细胞PVN中促肾上腺皮质激素释放激素（CRH）和血管加压素mRNA的表达，并刺激了未孕大鼠大细胞视上核和PVN催产素神经元中的Fos表达，但对妊娠大鼠无此作用。NPY对未孕大鼠和妊娠大鼠的食物摄入量和饮水量的增加作用相似。因此，妊娠晚期对中枢NPY的神经内分泌应激反应缺失，而摄食行为反应则完好无损。这些变化可能解释了对中枢给予的食欲肽A的HPA反应同样减弱的现象，并有利于妊娠期间的合成代谢适应。
