Laboratory of Neuropharmacology, Institute of Medical Biochemistry and Laboratory Diagnostics of the First Faculty of Medicine, Charles University, Albertov 4, 128 00, Prague 2, Czech Republic.
Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia.
Cell Mol Neurobiol. 2018 Jan;38(1):163-169. doi: 10.1007/s10571-017-0556-3. Epub 2017 Oct 9.
The activation of the HPA axis is the endocrine measure of stress responsiveness that is initiated by corticotropin-releasing hormone (CRH). CRH exerts its effects via CRHR1 and CRH-R2 receptors coupled to the cAMP signaling system and this process involves transcription factor cAMP-responsive element-binding protein (CREB).This study investigated the role of CRH and the possible involvement of CREB in gene regulation of CRH receptor, under basal conditions and after stress application in the pituitary. We used wild type (wt +/+) controls and CRH knock-out (CRH-KO -/-) male mice. Using CRH-deficient mice, we were able to investigate the consequences of the lack of the CRH on the expression of CRH receptors and transcriptional regulation mediated by CREB. We estimated the effect of acute (IMO 1×) and repeated (IMO 7×) restraint stressors lasting 30 and 120 min on the expression of mRNA CREB, CRH-R1, and CRH-R2 by qPCR. We found very significant difference in the expression of these peptides under the effect of single and repeated stress in control and CRH-KO mice. Our results indicate that both CRH receptors and CREB might be involved in the regulation of stress response in the pituitary of mice. We propose that regulation of the stress response may be better understood if more were known about the mechanisms of CRH receptor signal transduction and involvement of CREB system.
HPA 轴的激活是由促肾上腺皮质激素释放激素(CRH)引发的应激反应的内分泌测量。CRH 通过 CRHR1 和 CRH-R2 受体发挥作用,这些受体与 cAMP 信号系统偶联,这个过程涉及转录因子 cAMP 反应元件结合蛋白(CREB)。本研究探讨了 CRH 的作用以及 CREB 参与 CRH 受体基因调节的可能性,研究对象为基础条件下和垂体应激应用后的野生型(wt +/ +)对照和 CRH 敲除(CRH-KO -/-)雄性小鼠。使用 CRH 缺乏型小鼠,我们能够研究缺乏 CRH 对 CRH 受体表达和由 CREB 介导的转录调节的影响。我们通过 qPCR 估计了单次(IMO 1×)和重复(IMO 7×)应激(持续 30 和 120 分钟)对 CREB、CRH-R1 和 CRH-R2 mRNA 表达的影响。我们发现,在对照和 CRH-KO 小鼠中,这些肽在单一和重复应激的影响下的表达存在显著差异。我们的研究结果表明,CRH 受体和 CREB 可能都参与了小鼠垂体对应激反应的调节。我们提出,如果对 CRH 受体信号转导机制和 CREB 系统的参与有更多的了解,那么对调节应激反应的机制可能会有更好的理解。