Gartside S E, Suaud-Chagny M F, Tappaz M
Inserm U 171 and CNRS URA 1195, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France.
Neuroendocrinology. 1995 Jul;62(1):2-12. doi: 10.1159/000126982.
The paraventricular nucleus (PVN) of the hypothalamus, where the CRF-containing neurosecretory cells controlling the hypothalamo-pituitary-adrenal (HPA) axis are located, receives a dense noradrenergic innervation from the A1 group of the caudal ventrolateral medulla. In the present study we studied the relationship between release of noradrenaline (NA) in the PVN and activation of the HPA axis in response to electrical stimulation of the A1 region. In the urethane-anesthetized male rat, extracellular NA in the PVN was monitored on line by electrochemical recording while the activity of the HPA axis was estimated by measurement of ACTH in blood samples. A 1 min, 10 Hz stimulation evoked a significant increase of extracellular NA in the PVN as well as an ACTH surge in blood. The NA and ACTH response evoked by stimulation in the 3- to 14-Hz range were found to be frequency dependent. However, whilst the NA response increased in an exponential manner with respect to frequency, the ACTH response appeared to plateau between 10 and 14 Hz. Specific lesions of the noradrenergic terminals in the PVN, by bilateral local administration of 6-hydroxydopamine, markedly reduced the ACTH response to stimulation. Intracerebroventricular injection of desmethylimipramine, a NA uptake inhibitor, enhanced the increase in extracellular NA evoked by submaximal stimulation about 2.5-fold but did not modify the corresponding ACTH response. Combined intracerebroventricular injection of alpha- and beta-adrenergic antagonists, phentolamine and propanolol respectively, did not prevent the ACTH response evoked by stimulation. Following stimulation of the caudal ventrolateral medulla, the ACTH response thus appears to result from the stimulation of the A1 noradrenergic group projecting to the PVN. However, the inability of pharmacological manipulations which enhance or block central noradrenergic transmission to influence the ACTH response suggests that the noradrenergic endings in the PVN originating from the A1 group use a transmitter other than NA to activate the HPA axis at the PVN level.
下丘脑室旁核（PVN）是控制下丘脑 - 垂体 - 肾上腺（HPA）轴的含促肾上腺皮质激素释放因子（CRF）神经分泌细胞所在的部位，它接受来自延髓尾端腹外侧A1组的密集去甲肾上腺素能神经支配。在本研究中，我们研究了PVN中去甲肾上腺素（NA）释放与响应A1区电刺激时HPA轴激活之间的关系。在乌拉坦麻醉的雄性大鼠中，通过电化学记录在线监测PVN中的细胞外NA，同时通过测量血样中的促肾上腺皮质激素（ACTH）来评估HPA轴的活性。1分钟、10赫兹的刺激引起PVN中细胞外NA显著增加以及血液中ACTH激增。发现在3至14赫兹范围内刺激所诱发的NA和ACTH反应是频率依赖性的。然而，虽然NA反应相对于频率呈指数方式增加，但ACTH反应在10至14赫兹之间似乎趋于平稳。通过双侧局部注射6 - 羟基多巴胺对PVN中去甲肾上腺素能终末进行特异性损伤，显著降低了ACTH对刺激的反应。脑室内注射去甲丙咪嗪（一种NA摄取抑制剂），使次最大刺激诱发的细胞外NA增加增强了约2.5倍，但未改变相应的ACTH反应。分别联合脑室内注射α - 和β - 肾上腺素能拮抗剂酚妥拉明和普萘洛尔，并未阻止刺激诱发的ACTH反应。因此，在刺激延髓尾端腹外侧后，ACTH反应似乎是由投射到PVN的A1去甲肾上腺素能组的刺激引起的。然而，增强或阻断中枢去甲肾上腺素能传递的药理学操作无法影响ACTH反应，这表明源自A1组的PVN中的去甲肾上腺素能末梢在PVN水平使用除NA以外的递质来激活HPA轴。
