Purinton Scott C, Wood Charles E
Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville 32610, USA.
J Physiol. 2002 Nov 1;544(3):919-29. doi: 10.1113/jphysiol.2002.025635.
In the fetal sheep, parturition is triggered by an increase in the activity of the fetal hypothalamus- pituitary-adrenal (HPA) axis which, in turn, augments the biosynthesis of oestrogen by the placenta. Parturition can be prevented or delayed by destruction of the paraventricular nucleus (PVN), pituitary or adrenal, or stimulated by infusions of adrenocorticotropin (ACTH) or glucocorticoids. We have previously reported that physiological increases in fetal plasma concentrations of oestradiol have a neuroendocrine effect to increase both basal and hypotension-stimulated ACTH secretion. The present study was performed to test the effect of oestradiol on the central baroreceptor and chemoreceptor reflex pathways. We used immunohistological techniques to identify various neuroanatomical regions which are activated by hypotension and, subsequently, those areas modified by oestrogen's action and baroreceptor and chemoreceptor denervation. We assessed cellular activation in these brain regions by immunostaining for Fos, the protein product of c-fos, an immediate early response gene. We found that oestradiol increased Fos abundance in nucleus tractus solitarius (NTS), rostral ventrolateral medulla (RVLM), and PVN, and augmented the increase in Fos in these regions in response to a 10 min period of brachiocephalic arterial occlusion (BCO). Carotid sinus denervation blocked the Fos response to BCO, but not to oestrogen alone, in these regions. In contrast, the hippocampus responded to BCO with increase Fos in intact fetuses, but did not respond to oestrogen treatment. None of the treatments altered Fos expression in cerebral cortex or in cerebellum. We conclude that oestradiol augments the activity of the central baroreceptor and chemoreceptor reflex pathways, and that it may influence fetal ACTH secretion via this site of action.
在胎羊中，分娩是由胎儿下丘脑 - 垂体 - 肾上腺（HPA）轴活动增加引发的，这反过来又会增强胎盘雌激素的生物合成。破坏室旁核（PVN）、垂体或肾上腺可预防或延迟分娩，而输注促肾上腺皮质激素（ACTH）或糖皮质激素则可刺激分娩。我们之前曾报道，胎儿血浆雌二醇浓度的生理性升高具有神经内分泌作用，可增加基础及低血压刺激的促肾上腺皮质激素分泌。本研究旨在测试雌二醇对中枢压力感受器和化学感受器反射通路的影响。我们使用免疫组织学技术来识别因低血压而被激活的各个神经解剖区域，以及随后因雌激素作用、压力感受器和化学感受器去神经支配而发生改变的区域。我们通过对即刻早期反应基因c - fos的蛋白质产物Fos进行免疫染色，评估这些脑区的细胞激活情况。我们发现，雌二醇增加了孤束核（NTS）、延髓头端腹外侧区（RVLM）和室旁核中Fos的丰度，并增强了这些区域在头臂动脉闭塞（BCO）10分钟期间Fos的增加。在这些区域，颈动脉窦去神经支配阻断了对BCO的Fos反应，但未阻断对单独雌激素的反应。相反，完整胎儿的海马体对BCO有反应，Fos增加，但对雌激素处理无反应。所有处理均未改变大脑皮层或小脑中Fos的表达。我们得出结论，雌二醇增强了中枢压力感受器和化学感受器反射通路的活性，并且它可能通过这一作用位点影响胎儿促肾上腺皮质激素的分泌。
