The interaction of Urocortin II and Urocortin III with amygdalar and hypothalamic cotricotropin-releasing factor (CRF) - Reflections on the regulation of the hypothalamic-pituitary-adrenal (HPA) axis

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 H and Ucn III on the central CRF and peripheral glucocorticoids in rats. Increasing doses (0.5-1-2-5 mu g/2 mu l) 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 mu g of UCN II and 2 and 5 mu g of UCN III in the 5 min experiments and by 5 mu g of UCN II and 0.5 and 5 mu g 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 mu g of UCN II and 0.5-2 mu g of UCN III decreasing, and 2 and 5 mu g of UCN II and 5 mu g of UCN III increasing the hormone concentration, respectively. The plasma corticosterone concentration was decreased by 1 and 2 mu g of UCN II and UCN III and increased by 0.5 and 5 mu g 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. (C) 2013 Elsevier Ltd. All rights reserved.