CHRONIC ANOVULATORY HYPERANDROGENISM: SORTING GENOTYPES

慢性无排卵雄激素过多症：基因型分类

• 批准号: 2674039
• 负责人: SELMA FELDMAN WITCHEL
• 金额: $ 9.8万
• 依托单位: CHILDREN'S HOSP PITTSBURGH/UPMC HLTH SYS
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-05 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2674039
• 关键词: SDS polyacrylamide gel electrophoresis; autoradiography; biomarker; blood tests; chronic disease /disorder; disease /disorder proneness /risk; female; female reproductive system disorder diagnosis; follicle stimulating hormone; genetic markers; genotype; gonadotropins; hormone receptor; hormone regulation /control mechanism; human genetic material tag; human subject; insulin sensitivity /resistance; longitudinal human study; nucleic acid sequence; polycystic ovary syndrome; polymerase chain reaction; precocious puberty; single strand conformation polymorphism; urinalysis; virilism

Chronic anovulatory hyperandrogenism is a common heterogeneous disorder of unknown etiology characterized by hirsutism, oligo/amenorrhea, anovulation, infertility, acne, hyperandrogenism, increased LH/FSH ratio, and insulin resistance. Because insulin resistance is often accompanied by known risk factors for coronary artery disease, it has been speculated that chronic anovulatory hyperandrogenism indicates a greater propensity for coronary artery disease. Recently, it has been suggested that premature pubic hair is a harbinger of chronic anovulatory hyperandrogenism. If this proves to be true, it may he possible to identify and intervene earlier in the subset of patients at risk for chronic anovulatory hyperandrogenism and its associated complications. Preliminary data supports genotype analysis of steroidogenic enzymes especially 21- hydroxylase (CYP21). The hypotheses of this proposal are: 1) pre- mature pubic hair precedes chronic anovulatory hyperandrogenism in some patients; 2) the abnormal gonadal and/or adrenal steroid production limits FSH secretion to below the threshold concentrations needed for ovulation and 3) there are useful genetic and/or hormonal markers associated with an increased risk for chronic anovulatory hyperandrogenism. Genotype analysis of candidate genes in conjunction with sequential evaluation of patients with premature/excessive virilization, serial determinations of gonadotropin excretion and repeated assessments of insulin sensitivity will be used to test these hypotheses. Correlation of clinical features with results of hormonal and genetic evaluations may help unravel the sequence of events leading to chronic anovulatory hyperandrogenism.

慢性无排卵性高雄激素血症是一种常见的异质性 以多毛症为特征的病因不明的疾病， 少月经/停经、无排卵、不孕、痤疮、高雄激素血症， LH/FSH比值升高和胰岛素抵抗。因为胰岛素 阻力通常伴随着已知的冠状动脉粥样硬化的危险因素。 动脉疾病，据推测，慢性无排卵 高雄激素血症表明冠状动脉 疾病最近，有人提出，过早的阴毛 是慢性无排卵高雄激素血症的先兆。如果这 如果事实证明是真的，就有可能识别和干预 在慢性无排卵风险患者亚组中， 高雄激素血症及其相关并发症。初步数据 支持类固醇生成酶的基因型分析，特别是21- 羟化酶（CYP 21）。该方案的假设是：1）预- 成熟阴毛先于慢性无排卵高雄激素血症 部分患者：2）性腺和/或肾上腺类固醇异常 产生将FSH分泌限制在阈值以下 排卵所需的浓度和3）有有用的遗传 和/或与以下风险增加相关的激素标记物： 慢性无排卵性高雄激素血症基因型分析 候选基因与序贯评价 过早/过度男性化的患者，连续 促性腺激素排泄测定和重复评估 胰岛素敏感性将被用来测试这些假设。 临床特征与激素和 遗传评估可能有助于揭示导致遗传病的一系列事件， 慢性无排卵性高雄激素血症