MECHANISMS OF NEUROENDOCRINE REGULATION

研究的重点是相互作用的机制 对照组中的皮质酮释放激素(CRH)和其他调节剂 在正常情况下和在 适应压力。 两种不同品系大鼠衰老过程的研究 对应激的反应性，表现为脑垂体CRH浓度降低 老年大鼠的受体。尽管两个菌株的受体都减少了， 基础和应激刺激的ACTH水平与幼年大鼠相当。 然而，应激诱导的皮质酮反应在老年人中延长更多。 老鼠。这些数据表明，肾上腺对ACTH的反应性存在缺陷 可能在下丘脑-垂体的改变中起重要作用 衰老过程中的肾上腺轴。先前的研究表明，持续的压力是 伴随着垂体CRH受体和垂体的减少 对初级压力脱敏，但对新奇的 压力。通过分析CRH和VP在上述变化中的作用。 大鼠血浆促肾上腺皮质激素和皮质酮对急性应激的反应 慢性微量泵输注CRH单独或联合VP。CRH和 CRH加VP输注引起CRH受体的预期下降，但在 与慢性应激的变化相比，ACTH对急性应激的反应 在接受输液的大鼠中显著减少。血浆促肾上腺皮质激素 对急性CRH或CRH加VP注射的反应以及可释放的ACTH 用40 mM KCL刺激体外测量的池也减少了 在慢性CRH治疗后。数据表明，持续性脑下垂体 解释慢性疾病期间ACTH对一种新刺激的反应增强 压力。 前脑神经细胞培养的研究表明CRH刺激 环状AMP生产。类似于脑下垂体，这种作用被增强了。 通过蛋白激酶C刺激物VP和佛波酯，并被抑制 糖皮质激素。该数据支持CRH在调节 下丘脑外神经元功能。

Investigation has focused in the mechanisms of interaction between corticosterone releasing hormone (CRH) and other regulators in the control of the hypothalamic-pituitary-adrenal axis in normal conditions and during adaptation to stress. Studies during aging in two strains of rats which differ in their responsiveness to stress, showed reduced concentration of pituitary CRH receptors in old rats. Despite the decrease in receptors in both strains, basal and stress stimulated ACTH were comparable to those in young rats. However, stress induced corticosterone responses were more prolonged in old rats. These data suggest that a defect in adrenal responsiveness to ACTH may have an important role in the alterations of the hypothalamic-pituitary adrenal axis during aging. Previous studies showed that sustained stress is accompanied by decreases in pituitary CRH receptors and pituitary desensitization to the primary stress, but a hypersensitivity to a novel stress. The role of CRH and VP on these changes were studied by analysis of plasma ACTH and corticosterone responses to acute stress in rats receiving chronic minipump infusions of CRH alone or in combination with VP. CRH and CRH plus VP infusion caused the expected decrease in CRH receptors, but in contrast with the changes in chronic stress, ACTH responses to acute stress were markedly reduced in rats receiving the infusions. Plasma ACTH responses to acute CRH or CRH plus VP injection, as well as releasable ACTH pools measured in vitro by stimulation with 40 mM KCL were also reduced following chronic CRH treatment. The data indicate that sustained pituitary account for the enhanced ACTH responses to a novel stimulus during chronic stress. Studies in forebrain neuronal cell cultures showed that CRH stimulates cyclic AMP production. Similar to the pituitary, this effect was enhanced by the protein kinase C stimulators VP and phorbol esters, and inhibited by glucocorticoids. The data supports a role for CRH in the regulation of extrahypothalamic neuronal function.