CORTISOL FEEDBACK IN DIURNAL RHYTHM OF HPA AXIS

糖皮质激素在应激时分泌， 科普压力所必需的生理反应。但安 过量的糖皮质激素对机体有害。照经上所 必须调节糖皮质激素的分泌，以防止 分泌过多这是通过负反馈来实现的， 的网站。分泌的关闭，在上升阶段， 应激后的皮质类固醇分泌被称为快速反馈。在 此外，还有一个电平敏感的反馈，它是成比例的 糖皮质激素的分泌量与应激源。该比例 反馈发生在压力之后的几个小时， 在体外的脑垂体中得到证实。除了压力导致的 糖皮质激素有很强的昼夜节律， 糖皮质激素的压力诱导的水平在顶点，而夹紧 糖皮质激素降到最低水平负反馈 明显参与调节这种节奏。这种昼夜节律提供了 一个自然主义的模型来理解这些不同的反馈类型。 这 一个研究糖皮质激素与神经元回路接口的项目 反馈及其对昼夜节律的影响。具体来说，有两个假设 测试：1）有一个关键的皮质醇低点， 使受体重新敏感并触发昼夜节律驱动;或2） 绝对水平没有高低之间的变化那么重要 节奏的点，即，平坦的节律会产生 皮质醇反馈为了验证这些假设，三种不同的皮质酮 在天顶施用的不同作用时间的制剂与 将测量施用的时间节律的最低点。 糖皮质 反馈将用两种范式来衡量--体外短期 垂体前叶悬浮液和体内使用应力快速反馈 模型这种快速反馈模型测试了神经元回路的能力， 终止应激诱导CRH释放。这些反馈的变化 测量将与糖皮质激素的直接测量相关 海马体、下丘脑和垂体前叶中的受体。等 研究将有助于分类，如果有反馈的变化， 依赖于糖皮质激素受体的变化，并提供范例 来研究这些反馈的机制。这些 这些研究将为研究 抑郁症患者大脑HPA轴的变化。

Glucocorticoids are secreted in times of stress to provide a host of physiological responses necessary to cope with the stress. However, an excess of glucocorticoids are harmful to the organism. Thus, it is necessary to regulate secretion of glucocorticoids to prevent over-secretion. This is accomplished through negative feedback at a number of sites. The turning off of secretion during the rising phase of corticosteroid secretion following stress is known as fast feedback. In addition, there is a level sensitive feedback that is proportional to the amount of glucocorticoid secreted with the stressor. This proportional feedback occurs several hours following the stress and is easily demonstrated in vitro at the pituitary. Besides stress induced rises in glucocorticoid there is a strong circadian rhythm that drives glucocorticoids to stress induced levels at the zenith while clamping glucocorticoids to very low levels at the nadir. Negative feedback is clearly involved in regulating this rhythm. This circadian rhythm provides a naturalistic model for understanding these various feedback types. This project examines the interface of neuronal circuits with glucocorticoid feedback and its impact on circadian rhythm. Specifically, two hypotheses are tested: 1) that there is a critical low point of cortisol necessary to resensitize the receptor and trigger the circadian drive; or 2) that absolute levels are less critical than a variation between the high and low points of the rhythm, i.e., a flattened rhythm produces abnormalities of cortisol feedback. To test these hypotheses, three different corticosterone preparations of varying lengths of action administered in the zenith vs. the nadir of the time rhythm will be measured administered. Glucocorticoid feedback will be measured with two paradigms -- in vitro in short-term anterior pituitary suspensions and in vivo using a stress-fast feedback model. This fast feedback model tests the ability of neuronal circuits to terminate stress induced CRH release. The changes in these feedback measures will be correlated with direct measurement of glucocorticoid receptors in the hippocampus, hypothalamus and anterior pituitary. Such studies will help in sorting out if there are feedback changes that are not dependent upon changes in glucocorticoid receptors, and provide paradigms for studying the mechanisms underlying these forms of feedback. These studies will provide further leads for studying the connection between the brains's role in HPA axis changes in depression.