Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
Am J Physiol Endocrinol Metab. 2011 Jul;301(1):E72-82. doi: 10.1152/ajpendo.00695.2010. Epub 2011 May 3.
Although it is known that urocortin 1 (UCN) acts on both corticotropin-releasing factor receptors (CRF(1) and CRF(2)), the mechanisms underlying UCN-induced anorexia remain unclear. In contrast, ghrelin, the endogenous ligand for the growth hormone secretagogue receptor, stimulates food intake. In the present study, we examined the effects of CRF(1) and CRF(2) receptor antagonists (CRF(1)a and CRF(2)a) on ghrelin secretion and synthesis, c-fos mRNA expression in the caudal brain stem, and food intake following intracerebroventricular administration of UCN. Eight-week-old, male Sprague-Dawley rats were used after 24-h food deprivation. Acylated and des-acylated ghrelin levels were measured by enzyme-linked immunosorbent assay. The mRNA expressions of preproghrelin and c-fos were measured by real-time RT-PCR. The present study provided the following important insights into the mechanisms underlying the anorectic effects of UCN: 1) UCN increased acylated and des-acylated ghrelin levels in the gastric body and decreased their levels in the plasma; 2) UCN decreased preproghrelin mRNA levels in the gastric body; 3) UCN-induced reduction of plasma ghrelin and food intake were restored by CRF(2)a but not CRF(1)a; 4) UCN-induced increase of c-fos mRNA levels in the caudal brain stem containing the nucleus of the solitary tract (NTS) was inhibited by CRF(2)a; and 5) UCN-induced reduction of food intake was restored by exogenous ghrelin and rikkunshito, an endogenous ghrelin secretion regulator. Thus, UCN increases neuronal activation in the caudal brain stem containing NTS via CRF(2) receptors, which may be related to UCN-induced inhibition of both ghrelin secretion and food intake.
虽然已知孤啡肽 1（UCN）作用于促肾上腺皮质激素释放因子受体（CRF(1)和 CRF(2)），但 UCN 诱导厌食的机制尚不清楚。相比之下，生长激素促分泌素受体的内源性配体胃饥饿素刺激食物摄入。在本研究中，我们检查了 CRF(1)和 CRF(2)受体拮抗剂（CRF(1)a 和 CRF(2)a）对 UCN 脑室内给药后胃饥饿素分泌和合成、尾状脑干 c-fos mRNA 表达和食物摄入的影响。使用经过 24 小时禁食的 8 周龄雄性 Sprague-Dawley 大鼠。通过酶联免疫吸附试验测量酰化和去酰化胃饥饿素水平。通过实时 RT-PCR 测量 preproghrelin 和 c-fos 的 mRNA 表达。本研究提供了关于 UCN 厌食作用机制的以下重要见解：1）UCN 增加胃体中的酰化和去酰化胃饥饿素水平，降低血浆中的水平；2）UCN 降低胃体中的 preproghrelin mRNA 水平；3）CRF(2)a 而非 CRF(1)a 恢复 UCN 诱导的血浆胃饥饿素和食物摄入减少；4）UCN 诱导的尾状脑干中含有孤束核（NTS）的 c-fos mRNA 水平增加被 CRF(2)a 抑制；和 5）外源性胃饥饿素和 rikkunshito（一种内源性胃饥饿素分泌调节剂）恢复了 UCN 诱导的食物摄入减少。因此，UCN 通过 CRF(2)受体增加含有 NTS 的尾状脑干中的神经元激活，这可能与 UCN 诱导的胃饥饿素分泌和食物摄入抑制有关。
