REPRODUCTIVE AGING AND THE HUMAN HYPOTHALAMUS

生殖衰老和人类下丘脑

• 批准号: 3453455
• 负责人: NAOMI E RANCE
• 金额: $ 9.87万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-06-01 至 1996-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3453455
• 关键词: aging; digital imaging; estrogen receptors; estrogens; female; gender difference; gonadotropins; hormone regulation /control mechanism; human tissue; hypertrophy; hypothalamus; in situ hybridization; laboratory rat; male; microscopy; neuroanatomy; neuroendocrine system; neurotransmitters; ovariectomy; postmenopause; postmortem

Menopause marks the cessation of a dynamic physiological system regulating the cyclic release of pituitary and ovarian hormones. Due to an irreversible loss of ovarian follicles there is a marked decline in the production of steroids. Serum levels of gonadotropins become elevated, presumably due to the lack of steroid negative feedback on higher centers. The site of this steroid negative feedback in the human is unknown. Our preliminary studies demonstrate hypertrophy of neurons containing estrogen receptor gene transcripts in the infundibular nucleus of postmenopausal women. We hypothesize that postmenopausal neuronal hypertrophy is secondary to the withdrawal of the inhibitory feedback effects of ovarian steroids and not due to aging per se. The proposed studies are designed to test this hypothesis and determine the specificity of neuronal hypertrophy in the infundibular nucleus of postmenopausal females. Morphometric methods and computer microscopy will be used to measure neuronal cross-sectional areas in various, hypothalamic regions of pre- and postmenopausal women. We will also measure neuronal cross-sectional areas in the infundibular nucleus of young ovariectomized women, women with estrogen replacement therapy, and men. In situ hybridization will be used to determine the neurotransmitter content of the hypertrophied neurons. Finally, we will establish an experimental model of postmenopausal neuronal hypertrophy in laboratory rats by removing the ovaries. These studies will provide new information concerning the physiology of postmenopausal females, the control of reproductive function in humans, and the relationship between gonadal and neuroendocrine aging. Moreover, because postmenopausal neuronal hypertrophy represents an early, dramatic age-associated change in the human. brain, these studies will provide new insights into normal human aging and age-associated disease.

更年期标志着一种动态生理系统调节的停止 脑下垂体和卵巢激素的循环释放。由于 卵巢卵泡不可逆转的丢失有明显的下降 类固醇的生产。血清促性腺激素水平升高， 可能是由于高级中枢缺乏类固醇负反馈所致。 这种类固醇负反馈在人体内的位置尚不清楚。我们的 初步研究表明含有雌激素的神经元肥大 绝经后漏斗核受体基因转录本的研究 女人。我们假设绝经后神经元肥大是 继发性戒断对卵巢的抑制反馈作用 类固醇本身并不是由于衰老所致。建议的研究是设计的 为了检验这一假说并确定神经元的特异性 绝经后女性漏斗核肥大。 将使用形态测量方法和计算机显微镜来测量 大鼠下丘脑不同区域的神经元横截面积 绝经后的女性。我们还将测量神经元的横截面积。 在年轻的卵巢切除妇女的漏斗核中， 雌激素替代疗法和男性。将使用原位杂交 测定肥大神经元的神经递质含量。 最后，我们将建立一个绝经后神经元的实验模型。 通过摘除卵巢使实验大鼠肥大。这些研究将 提供有关绝经后生理学的新信息 女性，人类生殖功能的控制，以及 性腺与神经内分泌衰老的关系。此外，因为 绝经后神经元肥大表现为早期、戏剧性的 人类的年龄相关变化。大脑，这些研究将提供新的 对人类正常衰老和年龄相关疾病的洞察。