SEX HORMONE EFFECTS ON LIPOPROTEIN SPECIATION

性激素对脂蛋白形态的影响

• 批准号: 2227021
• 负责人: ROBERT B JAFFE
• 金额: $ 21.01万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-04-01 至 1998-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2227021
• 关键词: androgens; atherosclerosis; coronary disorder; electron microscopy; endocrine disorder chemotherapy; estrogens; female; gonadotropin releasing factor; high density lipoproteins; hormone binding protein; hormone therapy; human subject; immunologic assay /test; low density lipoprotein; polycystic ovary syndrome; postmenopause; progestins; radioimmunoassay; sex cycle; sex hormones; ultracentrifugation; women's health

Forty-three million women will reach the age of 50 in the United States in this decade, and coronary artery disease (CAD) will be the leading cause of death in this group. Therefore, it is imperative to understand the risk factors which contribute to the pathophysiology of CAD. Among these, alterations in lipoproteins play a major role. However, much remains to be learned about the various forms of high and low density lipoproteins (HDL and LDL) and their regulation. Therefore, the goal of this study is to elucidate the effects of endogenous and exogenous estrogens, progestins and androgens on speciation of HDL and LDL composition in reproductive age and postmenopausal women. To achieve this goal, studies will be performed in three groups of women: 1) women with normal menstrual cycles [before and after administration of a gonadotropin releasing hormone (GnRH) analog] ; 2) hyperandrogenic women of reproductive age (before and after administration of a GnRH analog with and without added estrogen] ; and 3) postmenopausal women [one group without exogenous steroids, one group receiving estrogen only, and a third group receiving estrogen plus progestin]. Women in all studies will have gonadotropins, sex steroids (estrogens, androgens, progesterone), and sex hormone binding globulin, measured by radioimmunoassay. These measurements will be correlated with the distribution of newly identified native species of HDL as assessed by selected affinity immunosorption and immunoassays, and with the quantized speciation state of LDL as assessed by gradient ultracentrifugation and electron microscopy. These correlations will provide new insights into the relationships between sex steroid hormone milieu, age and lipoproteins, and should lend to greater understanding of the etiology, treatment and prevention of CAD in women.

在美国，有400万妇女将达到50岁 这十年，冠状动脉疾病（CAD）将是主要原因 这组死亡。因此，必须了解风险 有助于CAD的病理生理的因素。其中， 脂蛋白的改变起主要作用。但是，还有很多事情要 了解各种形式的高密度脂蛋白（HDL） 和LDL）及其监管。 因此，这项研究的目的是阐明 内源性和外源性雌激素，孕激素和雄激素的物种形成 在生殖年龄和绝经后妇女中的HDL和LDL组成。 为了实现这一目标，将在三组妇女中进行研究： 1）经期正常的女性[给药前后 促性腺激素释放激素（GNRH）类似物]； 2）女性高雌激素 生殖年龄（给予GnRH类似物之前和之后 并且没有添加的雌激素]； 3）绝经后妇女[一组 没有外源性类固醇，一组仅接受雌激素，三分之一 接受雌激素加孕激素的组。所有研究中的妇女都会有 促性腺激素，性类固醇（雌激素，雄激素，孕酮）和性 激素结合球蛋白，通过放射免疫测定法测量。这些测量值 将与新确定的本地的分布相关 通过选定的亲和力免疫吸附和 免疫测定，并具有评估的LDL的量化物种状态 通过梯度超速离心和电子显微镜。这些 相关性将为性别之间的关系提供新的见解 类固醇激素环境，年龄和脂蛋白，应延长 了解女性的病因，治疗和预防CAD。