Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary.
Neuropeptides. 2013 Oct;47(5):333-8. doi: 10.1016/j.npep.2013.07.001. Epub 2013 Aug 7.
Urocortin II (Ucn II) and Urocortin III (Ucn III) are selective agonists of the CRF receptor type 2 (CRFR2). The aim of the present experiments was to investigate the effects of Ucn II and Ucn III on the central CRF and peripheral glucocorticoids in rats. Increasing doses (0.5-1-2-5 μg/2 μl) of Ucn II or Ucn III were administered intracerebroventricularly, then CRF concentration was determined by immunoassays in two different brain regions, the amygdala and the hypothalamus, and in two different time paradigms, 5 and 30 min after the administration of peptides. In parallel with the second determination, plasma corticosterone concentration was measured by chemofluorescent assay. The amygdalar CRF amount was increased significantly by 0.5 and 5 μg of UCN II and 2 and 5 μg of UCN III in the 5 min experiments and by 5 μg of UCN II and 0.5 and 5 μg of UCN III in the 30 min experiments. The hypothalamic CRF content was not affected considerably in the 5 min paradigm, but it was influenced significantly in the 30 min paradigm, with 0.5 and 1 μg of UCN II and 0.5-2 μg of UCN III decreasing, and 2 and 5 μg of UCN II and 5 μg of UCN III increasing the hormone concentration, respectively. The plasma corticosterone concentration was decreased by 1 and 2 μg of UCN II and UCN III and increased by 0.5 and 5 μg of UCN III. The present results demonstrate that central administration of Ucn II and Ucn III modulate time-dependently and dose-dependently the amygdalar and the hypothalamic CRF concentration, and, directly or indirectly, the plasma corticosterone concentration. The present experiments suggest that the role of CRFR2 in the regulation of the HPA axis can be inhibitory or stimulatory, depending on the actual concentration of their agonists.
尿皮质素 II(Ucn II)和尿皮质素 III(Ucn III)是 CRF 受体 2(CRFR2)的选择性激动剂。本实验的目的是研究 Ucn II 和 Ucn III 对大鼠中枢 CRF 和外周糖皮质激素的影响。给予递增剂量(0.5-1-2-5μg/2μl)的 Ucn II 或 Ucn III 脑室给药,然后通过免疫测定法在两个不同的脑区(杏仁核和下丘脑)和两个不同的时间模式(给药后 5 和 30 分钟)测定 CRF 浓度。在进行第二次测定的同时,通过化学荧光测定法测量血浆皮质酮浓度。在 5 分钟实验中,0.5 和 5μg 的 UCN II 和 2 和 5μg 的 UCN III 显著增加了杏仁核的 CRF 含量,而在 30 分钟实验中,0.5μg 的 UCN II 和 0.5 和 5μg 的 UCN III 增加了 CRF 含量。在 5 分钟实验中,下丘脑 CRF 含量没有明显变化,但在 30 分钟实验中,0.5 和 1μg 的 UCN II 和 0.5-2μg 的 UCN III 降低,而 2 和 5μg 的 UCN II 和 5μg 的 UCN III 分别增加了激素浓度。血浆皮质酮浓度被 1 和 2μg 的 UCN II 和 UCN III 降低,被 0.5 和 5μg 的 UCN III 增加。本研究结果表明,中枢给予 Ucn II 和 Ucn III 可时间依赖性和剂量依赖性地调节杏仁核和下丘脑 CRF 浓度,并直接或间接调节血浆皮质酮浓度。本实验表明,CRFR2 在 HPA 轴调节中的作用可能是抑制性的或刺激性的,这取决于其激动剂的实际浓度。