Effects of Chronic Estrogen on TIDA Neurons: Role of Cytokines and NO

慢性雌激素对 TIDA 神经元的影响：细胞因子和 NO 的作用

基本信息

批准号：
7843656
负责人：
PULIYUR S MOHANKUMAR
金额：
$ 23.38万
依托单位：
MICHIGAN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-04-15 至 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7843656
关键词：
Accounting Adult Affect Aging Animal Model Anterior Pituitary Gland Appearance Brain Brain region Cardiovascular Diseases Chronic Clinical Trials Complex Data Disease Dopamine Environmental Estrogen Estrogens Estrus Evaluation Exposure to Free Radical Alteration Free Radicals Health Hippocampus (Brain)Hormone replacement therapy Hormones Hyperprolactinemia Hypothalamic structure Laboratories Lead Life Mammary Neoplasms Mammary gland Mediating Menopause Metabolic Modeling Neurons Nitric Oxide Non-Insulin-Dependent Diabetes Mellitus Osteoporosis Perimenopause Phase Postmenopause Preparation Production Prolactin Rattus Reporting Research Personnel Risk Rodent Role Series Serum Stroke Structure of nucleus infundibularis hypothalami System Testing Tissues Tyrosine 3-Monooxygenase Woman Women&apos s Health age related base body system cardiovascular disorder risk cognitive function cytokine dopaminergic neuron interest malignant breast neoplasm median eminence neuronal cell body nitration novel programs proliferative phase Menstrual cycle reproductive research study tumor

项目摘要

Perimenopause is one of the most complex and least understood states of a woman's life. Many of the health risks associated with this state were believed to be due to decreases in estrogen levels and that estrogen could protect against health risks faced by perimenopausal women. However, estrogen fluctuates during perimenopause and if at all increases during the premenstrual and follicular phases. Recent clinical trials have shown that chronic administration of estrogenic compounds in postmenopausal women may increase the risk for several diseases. Therefore, it is important to investigate the effects of estrogen exposure on various organ systems. Studies so far indicate that estrogen's effects in the brain are beneficial. These reported effects, however, deal with non-hypothalamic regions of the brain. The effects of chronic estrogen exposure on the hypothalamus which regulates several key body functions have not been investigated. This is critical because women use estrogenic preparations on a prolonged basis and are exposed to endogenous estrogen throughout their adulthood. This proposal focuses on the effects of chronic estrogen exposure on one of the estrogen sensitive neuronal systems of the hypothalamus, namely, the tuberoinfundibular dopaminergic (TIDA) system. Dopamine (DA) released from TIDA neurons inhibits prolactin (PRL) secretion from the anterior pituitary. Age-related reductions in TIDA activity is associated with hyperprolactinemia and appearance of mammary and pitutiary tumors in animal models. The mechanisms behind the loss of TIDA neuronal function is not clear. In this application, we are proposing a novel hypothesis and an interesting model to study how estrogen could affect TIDA neurons and increase PRL levels. This series of studies is important because women not only use estrogen on a long-term basis in HRT but are also exposed to environmental estrogens. Prolonged exposure to estrogen and elevated levels of PRL may promote the risk for breast cancer.

围绕是女性生活中最复杂，最了解的状态之一。许多据信与该州相关的健康风险是由于雌激素水平的降低所致，并且雌激素可以预防绝经妇女面临的健康风险。但是，雌激素会波动在围绝经期间，如果在经前和卵泡相期间，根本增加了。最近的临床试验表明，绝经后女性的雌激素化合物的长期给药可能增加几种疾病的风险。因此，研究雌激素的影响很重要各种器官系统的暴露。到目前为止的研究表明，雌激素在大脑中的影响是有利。然而，这些报道的影响涉及大脑的非丘脑区域。效果下丘脑对调节几个关键身体功能的慢性雌激素暴露尚未调查。这是至关重要的，因为妇女长时间使用雌激素制剂，并且整个成年期都暴露于内源性雌激素。该提议着重于下丘脑的雌激素敏感神经元系统之一，即，慢性雌激素暴露，即结核菌多巴胺能（TIDA）系统。从TIDA神经元释放的多巴胺（DA）抑制垂体前垂体的催乳素（PRL）分泌。 TIDA活性与年龄相关的减少与动物模型中乳腺和亲肿瘤的高乳酸血症以及乳腺肿瘤的出现。机制 TIDA神经元功能丧失的背后尚不清楚。在此应用程序中，我们提出了一本小说假设和一个有趣的模型，用于研究雌激素如何影响TIDA神经元并增加PRL 水平。这一系列研究很重要，因为女性不仅在HRT中长期使用雌激素，而且也暴露于环境雌激素。长时间暴露于雌激素和PRL水平升高可能会促进乳腺癌的风险。

项目成果

期刊论文数量（22）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Metformin effectively restores the HPA axis function in diet-induced obese rats.

二甲双胍可有效恢复饮食诱导的肥胖大鼠的 HPA 轴功能。

DOI：
10.1038/s41366-020-00688-z
发表时间：
2021-03
期刊：
International journal of obesity (2005)
影响因子：
0
作者：
Shin AC;Balasubramanian P;Suryadevara P;Zyskowski J;Herdt TH;MohanKumar SMJ;MohanKumar PS
通讯作者：
MohanKumar PS

Differential effects of systemic interleukin-1β on gene expression in brainstem noradrenergic nuclei.

全身白介素-1β 对脑干去甲肾上腺素能核基因表达的不同影响。

DOI：
10.1016/j.lfs.2011.10.006
发表时间：
2012
期刊：
Life sciences
影响因子：
6.1
作者：
Sirivelu,MadhuP;MohanKumar,PS;MohanKumar,ShebaMJ
通讯作者：
MohanKumar,ShebaMJ

Chronic exposures to low levels of estradiol and their effects on the ovaries and reproductive hormones: Comparison with aging.

长期接触低水平雌二醇及其对卵巢和生殖激素的影响：与衰老的比较。

DOI：
10.4161/23273739.2014.967127
发表时间：
2014
期刊：
Endocrine disruptors (Austin, Tex.)
影响因子：
0
作者：
Gilbreath,EbonyT;MohanKumar,ShebaMJ;Balasubramanian,Priya;Agnew,DalenW;MohanKumar,PS
通讯作者：
MohanKumar,PS

Interleukin-1 beta simultaneously affects the stress and reproductive axes by modulating norepinephrine levels in different brain areas.

Interleukin-1 beta 通过调节不同大脑区域的去甲肾上腺素水平同时影响压力轴和生殖轴。