Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, 14049-900, Universidade de São Paulo, Ribeirão Preto, Sao Paulo, Brazil.
Endocrinology. 2012 Oct;153(10):4838-48. doi: 10.1210/en.2012-1333. Epub 2012 Aug 14.
CRH has been implicated as a mediator of stress-induced effects on the hypothalamus-pituitary-gonad axis, acting via CRH receptors in various brain regions. We investigated whether the effects of restraint stress on the secretion of gonadotropins on the morning of proestrus are mediated by the CRH-R1 or CRH-R2 receptors in the oval subdivision of the anterolateral BST, the central amygdala, the locus coeruleus (LC), or the A1 and A2 neuron groups in the medulla. At proestrus morning, rats were injected with antalarmin (a CRH-R1 antagonist), asstressin2-B (a CRH-R2 antagonist) or vehicles. Thirty minutes after the injection, the animals were placed into restraints for 30 min, and blood was sampled for 2 h. At the end of the experiment, the brains were removed for immunofluorescence analyses. Restraint stress increased the levels of FSH and LH. Antalarmin blocked the stress-induced increases in FSH and LH secretion, but astressin2-B only blocked the increase in FSH secretion. LC showed intense stress-induced neuronal activity. FOS/tyrosine-hydroxylase coexpression in LC was reduced by antalarmin, but not astressin2-B. The CRH-R1 receptor, more than CRH-R2 receptor, appears to be essential for the stimulation of the hypothalamus-pituitary-gonad axis by acute stress; this response is likely mediated in part by noradrenergic neurons in the LC. We postulate that the stress-induced facilitation of reproductive function is mediated, at least in part, by CRH action through CRH-R1 on noradrenaline neurons residing in the LC that trigger GnRH discharge and gonadotropin secretion.
CRH 被认为是介导应激对下丘脑-垂体-性腺轴影响的介质，通过各种脑区的 CRH 受体发挥作用。我们研究了束缚应激是否通过前外侧 BST 的卵形分叶、杏仁中央核、蓝斑（LC）或延髓的 A1 和 A2 神经元群中的 CRH-R1 或 CRH-R2 受体来调节动情前期早上促性腺激素的分泌。在动情前期早上，大鼠注射了 antalarmin（CRH-R1 拮抗剂）、astressin2-B（CRH-R2 拮抗剂）或载体。注射 30 分钟后，将动物置于束缚中 30 分钟，并采集血液 2 小时。实验结束时，取出大脑进行免疫荧光分析。束缚应激增加了 FSH 和 LH 的水平。Antalarmin 阻断了应激引起的 FSH 和 LH 分泌增加，但 astressin2-B 仅阻断了 FSH 分泌的增加。LC 显示出强烈的应激诱导的神经元活动。LC 中的 FOS/酪氨酸羟化酶共表达减少被 antalarmin 阻断，但不受 astressin2-B 影响。CRH-R1 受体，而不是 CRH-R2 受体，似乎是急性应激刺激下丘脑-垂体-性腺轴所必需的；这种反应可能部分通过 LC 中的去甲肾上腺素能神经元介导。我们推测，应激诱导的生殖功能促进至少部分是通过 LC 中 CRH 通过 CRH-R1 作用于去甲肾上腺素能神经元来介导的，这些神经元触发 GnRH 释放和促性腺激素分泌。
