NEURAL MECHANISMS OF CORTISOL SUPPRESSION

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。为了确定是否心理社会诱导的皮质醇抑制在社会下属的雌性绒猴介导的，部分，在大脑或垂体水平的内分泌抑制，作为一个模型，了解慢性内分泌失调与各种人类神经精神疾病。 皮质醇减少症，或肾上腺皮质皮质醇分泌不足，可能是人类早期或创伤应激的结果，并可能在许多应激相关疾病的病理生理学中发挥作用;然而，很少有动物模型可用于研究潜在的机制。雌性普通绒猴提供了一个有希望的灵长类动物模型，与压力相关的皮质醇减少，因为它们在成为社会群体的下属后，循环皮质醇会长期减少。在这项研究中，我们处理的主导和从属女性与皮质醇合成抑制剂甲吡酮和促肾上腺皮质激素释放因子（CRF），表征从属的影响下丘脑-垂体-肾上腺轴的中央调节。7个占主导地位的和6个下属的女性与CRF，预处理与甲吡酮或水。血浆促肾上腺皮质激素（ACTH）和皮质醇浓度测定前甲吡酮或水处理，随后，CRF治疗后。甲吡酮治疗后，下属有类似的皮质醇水平占主导地位，但显着较高的促肾上腺皮质激素水平。在CRF的挑战，皮质醇浓度较低，ACTH浓度较高的下属，虽然净综合反应CRF没有不同。皮质醇促肾上腺皮质激素的比例始终较低的下属。这些结果证实了以前的研究结果，低皮质醇浓度和迟钝的肾上腺反应的下属，并建议，当皮质醇水平的差异被消除，下属表现出夸张的下丘脑驱动垂体。这些神经内分泌的变化在下级绒猴类似于创伤后应激障碍患者和成年幸存者的虐待儿童。本研究使用WNPRC Animal Services（绒猴群）和Assay Services。

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 determine whether psychosocially induced suppression of cortisol in socially subordinate female marmosets is mediated, in part, by endocrine inhibition at the level of the brain or pituitary, as a model for understanding chronic endocrine dysregulation associated with a variety of human neuropsychiatric disorders. Hypocortisolism, or insufficient secretion of cortisol from the adrenal cortex, may occur in humans as a consequence of early or traumatic stress and may play a fole in the pathophysiology of numerous stress-related disorders; however, few animal models are available for investigation of the underlying mechanisms. Female common marmosets offer a promising primate model of stress-related hypocortisolism, as they undergo chronic reductions in circulating cortisol after becoming subordinate in a social group. In this study, we treated dominant and subordinate females with the cortisol synthesis inhibitor metyrapone and corticotropin-releasing factor (CRF), to characterize the effects of subordination on central regulation of the hypothalamic-pituitary-adrenal axis. Seven dominant and six subordinate females were treated with CRF, following pretreatment with metyrapone or water. Plasma adrenocorticotropin (ACTH) and cortisol concentrations were determined before metyrapone or water treatment, and, subsequently, after CRF treatment. Following metyrapone treatment, subordinates had similar cortisol levels to dominants, but significantly higher ACTH levels. During CRF challenges, cortisol concentrations were lower and ACTH concentrations higher in subordinates, although net integrated responses to CRF did not differ. Cortisol-to-ACTH ratios were consistently lower in subordinates. These results confirm previous findings of low cortisol concentrations and blunted adrenal responsiveness in subordinates, and suggest that when differences in cortisol levels are eliminated, subordinates exhibit exaggerated hypothalamic drive to the pituitary. These neuroendocrine alterations in subordinate marmosets resemble those in posttraumatic stress disorder patients and adult survivors of child abuse. This research used WNPRC Animal Services (marmoset colony) and Assay Services.