MOLECULAR ENDOCRINOLOGY OF THE UTERUS

子宫的分子内分泌学

• 批准号: 2024659
• 负责人: Elizabeth A Stewart
• 金额: $ 8.21万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2024659
• 关键词: chorionic gonadotropin; clinical research; endocrinology; endometrium; female; follicle stimulating hormone; genetic transcription; histopathology; hormone receptor; human subject; in situ hybridization; ligands; luteinizing hormone; molecular biology; molecular genetics; myometrium; northern blottings; nucleic acid probes; ovary; polymerase chain reaction; protein structure; receptor expression; thyrotropin; uterus

DESCRIPTION: (Adapted from applicant's description) The glycoprotein hormone human chorionic gonadotropin (hCG) has been demonstrated to have direct effects on uterine metabolism. hCG is a member of a family of dimeric hormones including luteinizing hormone (LH), follicle stimulating hormone (FSH) and thyrotropin (TSH), that share a common alpha subunit and have unique beta-subunits. Studies from the investigator's laboratory and others have suggested that the alpha-subunit of hCG has a role in the regulation of prolactin production by uterine myometrium and decidua. However, the mechanism of this effect is not understood because alpha-subunit alone appears to have no effect through the known LH/hCG receptor. Furthermore, although it has been hypothesized that there are receptors on non-gonadal tissues including human endometrium and myometrium for LH/hCG, these studies have significant limitations that compromise the power of their conclusions. The hypothesis is that a unique receptor transduces the actions of hCG and/or alpha-subunit in the human uterus. The aim of this proposal is to characterize, using the techniques of molecular biology and molecular genetics, the known receptors for these hormones and to clone a unique receptor in the human uterus. These studies will define potentially a new level of pituitary/uterine interaction independent of gonadal hormonal influences. They may also lead to a better understanding of the molecular endocrinology of the human uterus. The specific aims of this proposal are: 1. To clone a unique receptor for hCG and/or alpha-subunit in the human uterus. 2. To quantitate and determine physiologic expression for this unique receptor(s) in the human uterus. 3. To identify genes transcriptionally regulated by the action of the ligands for this receptor(s) in the human uterus.

描述：(根据申请者的描述改编)糖蛋白 激素人绒毛膜促性腺激素(HCG)已被证明具有 对子宫新陈代谢有直接影响。人绒毛膜促性腺激素是一种 促黄体生成素、卵泡刺激素等二聚体激素 激素(FSH)和促甲状腺激素(TSH)，它们共享一个共同的阿尔法亚单位和 有独特的β亚基。来自调查员实验室的研究和 其他人则认为hCG的阿尔法亚单位在 子宫肌层和蜕膜对催乳素产生的调节。 然而，这种效应的机制尚不清楚，因为 α-亚基单独通过已知的促黄体生成素/人绒毛膜促性腺激素似乎没有作用 受体。 此外，尽管已经假设有受体存在于 非性腺组织包括人子宫内膜和子宫肌层测定促黄体生成素/人绒毛膜促性腺激素， 这些研究有很大的局限性，损害了 他们的结论。假设是一种独特的受体转导 人绒毛膜促性腺激素和/或α-亚基在人子宫中的作用。这样做的目的是 建议是利用分子生物学和 分子遗传学，已知的这些激素的受体，并克隆一个 人类子宫中唯一的受体。 这些研究将潜在地定义一个新的垂体/子宫水平。 相互作用不受性腺激素的影响。他们也可能领先于 为了更好地了解人类的分子内分泌学 子宫。这项建议的具体目标是： 1.克隆人绒毛膜促性腺激素和/或α-亚基的独特受体 子宫。2.量化和测定其生理学表达 独一无二 人子宫中的受体(S)。3.从转录水平鉴定基因 受配体的作用调节 人类子宫中的这种受体(S)。