CORTICOTROPIN-RELEASING FACTOR IN HORMONAL AND BEHAVIORAL RESPONSES TO STRESS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。研究绒猴脑和垂体中促肾上腺皮质激素释放因子系统的特征，探讨其在应激的内分泌和行为反应中的作用。 促肾上腺皮质激素释放因子（CRF）是一种神经肽，可调节对压力的行为、激素、自主神经和免疫反应，可能与人类情绪和焦虑症的病理生理学有关。为了建立一个非人灵长类动物模型的CRF高分泌的内分泌和行为的影响，我们进行了试点测试的特点表达的CRF 1型（CRFR 1）和2型（CRFR 2）受体和CRF结合蛋白（CRF-BP）在绒猴垂体，并评估antalarmin的影响，选择性CRFR 1拮抗剂，对激素和行为的反应CRF和压力。发现绒猴CRFR 1、CRFR 2和CRF-BP的克隆区域的序列在DNA水平上与人类基因具有98%的同源性，并且对于CRFR 1和CRFR 2，扩增区域的预测蛋白质序列具有100%的同一性。克隆的绒猴CRF-BP基因与人CRF-BP基因在核酸水平上同源性为96%，在预测蛋白水平上同源性为98%。我们观察到，CRFR 1和CRFR 2 mRNA在绒猴脑垂体中的丰度几乎相等，这两种CRF受体对促肾上腺皮质激素（ACTH）的产生和分泌具有潜在的调节作用。Antalarmin减少了ACTH反应绵羊CRF以及ACTH和皮质醇反应的限制应激，但不改变基础血浆ACTH或皮质醇浓度。这些研究表明，CRF作用于CRFR 1刺激绒猴ACTH释放，但也表明CRF通过CRFR 2和/或其他促分泌素发挥作用，也可能在基线条件下调节ACTH释放中发挥重要作用。这些发现将为进一步研究CRF在绒猴应激反应中的作用奠定重要基础。本研究使用WNPRC绒猴群、分析服务和病理学服务。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To characterize the corticotropin-releasing factor system in the brain and pituitary of the marmoset and evaluate its role in endocrine and behavioral responses to stress. Corticotropin-releasing factor (CRF) is a neuropeptide that regulates the behavioral, hormonal, autonomic, and immune responses to stress and may contribute to the pathophysiology of mood and anxiety disorders in humans. To develop a nonhuman primate model of the endocrine and behavioral effects of CRF hypersecretion, we performed pilot tests characterizing the expression of CRF type-1 (CRFR1) and type-2 (CRFR2) receptors and CRF-binding protein (CRF-BP) in the marmoset pituitary, and assessing the effects of antalarmin, a selective CRFR1 antagonist, on hormonal and behavioral responses to CRF and stress. The sequences for the cloned regions of the marmoset CRFR1, CRFR2, and CRF-BP were found to be 98% homologous with the human genes at the DNA level, and for CRFR1 and CRFR2, 100% identity for the predicted protein sequence of the amplified region. The cloned region of the marmoset CRF-BP was found to be 96% homologous to human at the nucleic acid level and 98% identity at the predicted protein level. We observed that the CRFR1 and CRFR2 mRNAs were of nearly equal abundance in the marmoset pituitary, providing for potential regulation of adrenocorticotropin (ACTH) production and secretion by both of these CRF receptors in this species. Antalarmin reduced the ACTH response to ovine CRF as well as the ACTH and cortisol responses to a restraint stressor, but did not alter basal plasma ACTH or cortisol concentrations. These studies indicate that CRF acts on CRFR1 to stimulate ACTH release in the marmoset, but suggest that CRF acting through CRFR2, and/or other secretagogues, may also play a significant role in regulating ACTH release under baseline conditions. These findings will for a crucial basis for further studies of the role of CRF on responses to stress in the marmoset. This research used the WNPRC marmoset colony, Assay Services and Pathology Services.