Expression of corticotropin releasing hormone receptors type I and type II mRNA in suicide victims and controls
Expression of corticotropin releasing hormone receptors type I and type II mRNA in suicide victims and controls
复制标题
DOI：
10.1038/sj.mp.4000908
复制
发表时间：
2001-09-01
影响因子：
11
通讯作者：
Bornstein, SR
中科院分区：
文献类型：
--
作者：
Hiroi, N;Wong, ML;Bornstein, SR
促肾上腺皮质激素释放激素（CRH）是一种重要的神经内分泌因子，参与应激反应的内分泌、免疫和行为反应。CRH通过两种主要受体CRH-R1和CRH-R2发挥作用。最近，针对CRH-R1或CRH-R2的新型非肽拮抗剂已被提出作为治疗抑郁症、焦虑症和进食障碍的有前景的药物。然而，到目前为止，CRH受体系统尚未在人类中进行广泛研究。因此，我们采用定量TaqMan PCR技术分析CRH-R1和CRH-R2在人脑组织和外周器官中的表达和分布。并首次采用原位杂交和定量PCR技术分析了自杀者垂体CRH受体的表达。我们的数据表明，与啮齿动物相比，人类中的表达模式不同。CRH-R1和CRH-R2都在脑中大量表达，在垂体中表达最强。然而，如啮齿类动物中所述，人类CRH-R1是大脑中的主要受体（82.7 +/- 11.0%），而CRH-R2是外周器官中的主要受体（77.0 +/- 15.8%）。自杀者脑垂体CRH-R1/R2的比例发生了变化。总之，CRH-R1和GRH-R2在人类组织中广泛表达，其分布与啮齿动物基本不同。CRH-R1和CRH-R2在人垂体中的强表达表明，特别是在应激下，HPA轴的激活可以通过两种受体维持。
Corticotropin-releasing hormone (CRH) is a key neuroendocrine factor implementing endocrine, immune and behavioral responses to stress. CRH exerts its action through two major receptors, CRH-R1 and CRH-R2. Recently novel non-peptidic antagonists directed against CRH-R1 or CRH-R2 have been proposed as promising agents in the treatment of depression, anxiety and eating disorder. However, so far the CRH-receptor system has not been widely studied in humans. Therefore, we employed quantitative TaqMan PCR to analyze the expression and distribution of both CRH-R1 and CRH-R2 in human brain tissue and peripheral organs. Furthermore the expression of CRH receptors was analyzed for the first time in pituitaries of suicide victims by in situ hybridization and quantitative PCR. Our data demonstrated a different expression pattern in humans as compared to rodents. Both CRH-R1 and CRH-R2 were expressed in high amounts in the brain with the strongest expression in the pituitary. As described in rodents, however the CRH-R1 in human was the predominant receptor in the brain (82.7 +/- 11.0%), whilst CRH-R2 was the predominant receptor in peripheral organs (77.0 +/- 15.8%). There was a shift in the ratio of CRH-R1/R2 in the pituitaries of suicide victims. In conclusion, both CRH-R1 and GRH-R2 are widely expressed in human tissues with a distribution substantially different from rodents. Strong expression of both CRH-R1 and CRH-R2 in human pituitaries suggests that particularly under stress, activation of the HPA axis can be maintained through both receptors.