Li X F, Kinsey-Jones J S, Bowe J E, Wilkinson E S, Brain S D, Lightman S L, O'Byrne K T
Division of Reproduction & Endocrinology, London, UK.
Stress. 2009 May;12(3):259-67. doi: 10.1080/10253890802379922.
Calcitonin gene-related peptide (CGRP) is involved in a variety of stress responses and plays a pivotal role in stress-induced suppression of the GnRH pulse generator in the rat. Intracerebroventricular administration of CGRP suppresses luteinizing hormone (LH) pulses and increases Fos expression within the medial preoptic area (mPOA) and paraventricular nucleus (PVN). The aims of the present study were to investigate whether the mPOA or PVN are sites of action for CGRP-induced suppression of LH pulses and whether lipopolysaccharide (LPS), restraint or insulin-induced hypoglycaemia, stressors known to suppress LH pulses, affect mRNA expression for CGRP and its receptor subunits (calcitonin receptor-like receptor (CL) and RAMP-1) in the mPOA and PVN. Micro-infusion of CGRP (50, 250 or 500 pmol) into the mPOA, but not the PVN, dose-dependently suppressed LH pulse frequency. LPS, restraint and hypoglycaemia suppressed RAMP-1 mRNA, but not CL or CGRP mRNA expression in the mPOA. In the PVN, all three stressors suppressed CL mRNA expression, but only LPS or restraint suppressed RAMP-1 mRNA, and CGRP mRNA was unaffected. These results provide evidence that, unlike the PVN, the mPOA might play an important role in the inhibitory effect of CGRP on pulsatile LH secretion. Additionally, CGRP receptor function may be involved in this brain region in stress-induced suppression of the GnRH pulse generator.
降钙素基因相关肽（CGRP）参与多种应激反应，并在应激诱导的大鼠促性腺激素释放激素（GnRH）脉冲发生器抑制中起关键作用。脑室内注射CGRP可抑制促黄体生成素（LH）脉冲，并增加视前内侧区（mPOA）和室旁核（PVN）内的Fos表达。本研究的目的是调查mPOA或PVN是否是CGRP诱导的LH脉冲抑制的作用位点，以及脂多糖（LPS）、束缚或胰岛素诱导的低血糖（已知可抑制LH脉冲的应激源）是否会影响mPOA和PVN中CGRP及其受体亚基（降钙素受体样受体（CL）和受体活性修饰蛋白-1（RAMP-1））的mRNA表达。向mPOA而非PVN微量注射CGRP（50、250或500 pmol）可剂量依赖性地抑制LH脉冲频率。LPS、束缚和低血糖可抑制mPOA中RAMP-1 mRNA的表达，但不影响CL或CGRP mRNA的表达。在PVN中，所有三种应激源均可抑制CL mRNA的表达，但只有LPS或束缚可抑制RAMP-1 mRNA的表达，而CGRP mRNA不受影响。这些结果表明，与PVN不同，mPOA可能在CGRP对LH脉冲分泌的抑制作用中起重要作用。此外，CGRP受体功能可能参与该脑区对应激诱导的GnRH脉冲发生器的抑制作用。
