Nicot A, Rowe W B, De Kloet E R, Betancur C, Jessop D S, Lightman S L, Quirion R, Rostène W, Bérod A
INSERM U339, Centre de Recherche INSERM Saint-Antoine, Paris, France.
J Neuroendocrinol. 1997 Apr;9(4):263-9. doi: 10.1046/j.1365-2826.1997.00581.x.
Adrenocorticotropin (ACTH) secretion depends primarily on hypophysiotrophic factors released from neurons of the paraventricular nucleus of the hypothalamus. However, the neurochemical factors controlling these neurons, in particular neuropeptides, have had little investigation. In this study, we have investigated the role of neurotensin in the regulation of the different components of the hypothalamo-pituitary-adrenal (HPA) axis under basal and stress conditions in rats. For this purpose, animals were implanted with bilateral cannulae filled with crystals of the neurotensin antagonist, SR 48692, and which were located above the paraventricular nucleus. Five days after surgery, the effects of SR 48692 implants were studied on basal and stress-induced secretion of ACTH and corticosterone. Such treatment did not modify plasma levels of ACTH and corticosterone in basal conditions but reduced ACTH but not corticosterone levels after tail cut procedure. After an exposure to a novel environment for 30 min, both ACTH and corticosterone plasma levels were reduced in the SR 48692-treated group. In situ hybridization studies revealed that chronic administration of SR 48692 induced a significant reduction of CRF mRNA levels in the parvocellular division of the paraventricular nucleus of the hypothalamus. In addition, a 2-fold increase in basal levels of plasma vasopressin associated with an increase in vasopressin mRNA levels in the magnocellular neurons of the paraventricular nucleus was also detected. Finally, the basal plasma levels of oxytocin were not affected by the same treatment. Taken together, these findings strongly suggest that endogenous neurotensin in the paraventricular nucleus plays a tonic stimulatory role on HPA axis activity and an inhibitory effect on vasopressin secretion.
促肾上腺皮质激素（ACTH）的分泌主要取决于下丘脑室旁核神经元释放的促垂体激素因子。然而，控制这些神经元的神经化学因子，尤其是神经肽，鲜有研究。在本研究中，我们探究了神经降压素在基础和应激条件下对大鼠下丘脑 - 垂体 - 肾上腺（HPA）轴不同组成部分调节中的作用。为此，给动物双侧植入充满神经降压素拮抗剂SR 48692晶体的套管，且套管位于室旁核上方。术后5天，研究SR 48692植入物对基础和应激诱导的ACTH及皮质酮分泌的影响。这种处理在基础条件下未改变ACTH和皮质酮的血浆水平，但在剪尾处理后降低了ACTH水平，而未降低皮质酮水平。在暴露于新环境30分钟后，SR 48692处理组的ACTH和皮质酮血浆水平均降低。原位杂交研究表明，长期给予SR 48692可使下丘脑室旁核小细胞部的促肾上腺皮质激素释放因子（CRF）mRNA水平显著降低。此外，还检测到基础血浆血管加压素水平增加了2倍，同时室旁核大细胞神经元中血管加压素mRNA水平也增加。最后，相同处理未影响基础血浆催产素水平。综上所述，这些发现强烈表明，室旁核中的内源性神经降压素对HPA轴活动起紧张性刺激作用，对血管加压素分泌起抑制作用。
