HYPOTHALMO-PITUITARY-ADRENAL AXIS IN DEPRESSION

下丘脑-垂体-肾上腺轴抑郁

• 批准号: 2239818
• 负责人: ELIZABETH ANN YOUNG
• 金额: $ 7.47万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2239818
• 关键词: adrenocorticotropic hormone; circadian rhythms; corticosteroid receptors; corticosterone; cortisol; estradiol; female; follicle stimulating hormone; gonadotropin releasing factor; hormone regulation /control mechanism; human subject; hypothalamic pituitary axis; laboratory rat; luteinizing hormone; major depression; menstrual cycle; ovariectomy; peptide hormone biosynthesis; pituitary adrenal axis; pituitary gonadal axis; postmenopause; progesterone; secretion; stress; urinalysis

Future studies proposed in this application will continue to explore hormonal abnormalities in depression, with a shift in focus from solely HPA axis hormones to include interactions between the gonadal hormone axis and the stress axis. Depression is a disorder with a strong predilection for women. Abnormalities of several hormonal axes particularly the adrenal (stress) and thyroid axes have been well documented in depressed women, but few studies have explored the hypothalamic pituitary gonadal (HPG) axis. The occurrence of sex bias in the expression of depressive illness after the onset of puberty, as well as anecdotal studies suggesting an association between mood and cyclic gonadal steroid changes suggest that gonadal axis hormones may modulate the onset and course of depression. Hormones of the hypothalamic pituitary adrenal (HPA) axis have been demonstrated to affect the hypothalamic pituitary gonadal axis, particularly the secretion of gonadotropin releasing hormone (GnRH) from the hypothalamus. Hypothalamic amenorrhea, exercise induced amenorrhea and anorexia nervosa all demonstrate activation of the HPA axis accompanying the abnormalities in GnRH and LH secretion. This suggests that activation of the HPA axis is closely linked to abnormal GnRH secretion in humans. This project proposes to study the interactions between these two hormonal axes (stress and gonadal) to determine if depression in women is accompanied by abnormalities in reproductive axis hormones and if abnormalities in the reproductive axis are linked to abnormalities in the HPA axis, or if the two abnormalities can co-exist independently. To characterize baseline secretion in these two axes,l2 hour studies using 3 minute sampling will be conducted in depressed women to examine pulsatile secretion of the gonadal hormones (LH, FSH, estradiol and progesterone) as well as pulsatile secretion of the stress axis hormones (ACTH and cortisol). These data will be compared with data from control women matched for age and menstrual cycle day. In depressed women pulse frequency and amplitude of LH secretion will each be examined, as well as frequency and amplitude of ACTH and cortisol pulses. GnRH secretion, as assessed by LH secretion in the periphery, appears to be the most sensitive index of disruptions in HPG axis secretion, but gonadal steroid hormones will also be evaluated. HPA axis pulsatility data will determine if secretory drive in depressed women increases in the zenith and nadir of the circadian rhythm, and if the onset of circadian driven secretory episodes shift in depressed women. In normal women, the influence of gonadal axis hormones on HPA axis function will be explored by comparing the two axes and the response to dexamethasone at different phases of the menstrual cycle in a subgroup of the control women. In rats, we will examine the effect of ovariectomy and replacement with gonadal steroids on the negative feedback effects of exogenous glucocorticoids at multiple levels of the HPA axis as well as the effects on stress.

该应用程序中提出的未来研究将继续探索 抑郁症的激素异常，聚焦仅转移 HPA轴激素包括性腺激素轴之间的相互作用 和应力轴。抑郁症是一种强烈偏爱的疾病 对女性来说。几个激素轴特别是肾上腺的异常 （压力）和甲状腺轴已在沮丧的女性中得到充分证明 但是很少有研究探索下丘脑垂体性腺（HPG） 轴。性偏见在抑郁疾病表达中的发生 青春期发作后以及轶事研究表明 情绪与循环性腺类固醇变化之间的关联表明 性腺轴激素可能会调节抑郁症的发作和过程。 下丘脑垂体肾上腺（HPA）轴的激素已经是 证明会影响下丘脑垂体性性腺轴， 特别是促性腺激素释放激素（GNRH）的分泌 下丘脑。下丘脑闭经，运动诱导的闭经和 神经性厌食症都表现出伴随的HPA轴的激活 GnRH和LH分泌的异常。这表明激活 HPA轴与人类的GNRH分泌异常紧密相关。 该项目建议研究这两种激素之间的相互作用 轴（压力和性腺）以确定女性的抑郁症是否是 伴有生殖轴激素异常，如果 生殖轴异常与异常有关 HPA轴，或两个异常是否可以独立共存。到 在这两个轴上表征基线分泌，使用3个小时研究 分钟抽样将在抑郁的女性中进行检查以检查脉动 性腺激素（LH，FSH，雌二醇和孕酮）的分泌 以及应力轴激素的脉动分泌（ACTH和ACTH和 皮质醇）。这些数据将与对照妇女的数据进行比较 适合年龄和月经周期日。沮丧的女人脉搏 将检查LH分泌的频率和振幅 ACTH和皮质醇脉冲的频率和振幅。 GnRH分泌，AS 通过LH分泌在外围评估，似乎是最多的 HPG轴分泌中干扰的敏感指数，但性腺类固醇 激素也将进行评估。 HPA轴脉动数据将确定 如果在沮丧的妇女中分泌驱动力增加 昼夜节律，如果昼夜节律的分泌发作 情节在沮丧的女性中发生了变化。在普通女性中， 通过比较，将探索HPA轴功能上的性腺轴激素 两个轴和对地塞米松在不同阶段的反应 在对照妇女的子组中的月经周期。在老鼠中，我们会 检查卵巢切除术和用性腺类固醇替代的影响 外源性糖皮质激素在多个 HPA轴的水平以及对应力的影响。