Global Synchrony and Frequency Modulation in the Anterior Pituitary

垂体前叶的整体同步和频率调制

• 批准号: 0308956
• 负责人: Mary Lou Zeeman
• 金额: $ 11.52万
• 依托单位: University of Texas at San Antonio
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0308956&HistoricalAwards=false
• 关键词: Global; Synchrony; Frequency; Modulation; Anterior

The mechanism by which circulating estradiol initiates a surge of luteinizing hormone (LH) from the pituitary, thereby triggering ovulation, has remained a mystery of human physiology, despite two decades of intensive biological and medical research. The transient resonance model developed by the PI and her collaborators is the first mathematical model of the LH surge to unify the experimental data on multiple time scales with the surprising hormone replacement pulse frequency characteristics required to treat infertility disorders such as Kallmann's syndrome. The model predicts that the pituitary gland has an intrinsic rhythm that depends on levels of circulating steroids, and that pituitary response to pulsatile hypothalamic stimulus depends on frequency interactions between the hypothalamic and pituitary rhythms. The PI will spend a year working in the McCobb lab in the Department of Neurobiology and Behavior at Cornell University. The objectives are: (1) Learn the language and basic techniques of experimental neuroscience. (2) Experimentally test the model predictions by driving whole pituitaries in different steroid environments in vitro. (3) Collect preliminary data to develop mutually driven mathematical and experimental approaches to local (small cell networks) and global (whole pituitary) investigation of the broad ranging questions raised by the model about frequency interactions between different endocrine axes within the pituitary. Understanding the fundamental structure through which the hypothalamus and pituitary interact has a wealth of medical applications. For the hypothalamus-pituitary-gonad axis alone, these include ovarian and breast cancer, the passage to menopause, hormone replacement therapy, infertility diagnosis and treatment, and contraception.This IGMS project is jointly supported by the MPS Office of Multidisciplinary Activities (OMA) and the Division of Mathematical Sciences (DMS).

循环中的雌二醇通过何种机制引发垂体中促黄体生成激素（LH）的激增，从而触发排卵，尽管经过了二十年的深入生物学和医学研究，但这仍然是人类生理学的一个谜。PI及其合作者开发的瞬态共振模型是LH激增的第一个数学模型，将多个时间尺度上的实验数据与治疗不孕症（如卡尔曼综合征）所需的令人惊讶的激素替代脉冲频率特征统一起来。该模型预测，垂体有一个内在的节奏，取决于循环类固醇的水平，和垂体对脉动下丘脑刺激的反应取决于下丘脑和垂体节律之间的频率相互作用。 PI将在康奈尔大学神经生物学和行为系的McCobb实验室工作一年。目的：（1）学习实验神经科学的语言和基本技术。 (2)通过在体外不同类固醇环境中驱动整个垂体来实验性地测试模型预测。(3)收集初步数据，以开发相互驱动的数学和实验方法，以局部（小细胞网络）和全局（整个垂体）调查模型提出的关于垂体内不同内分泌轴之间频率相互作用的广泛问题。 了解下丘脑和垂体相互作用的基本结构具有丰富的医学应用。 仅就下丘脑-垂体-性腺轴而言，这些疾病包括卵巢癌和乳腺癌、绝经期、激素替代疗法、不孕症的诊断和治疗以及避孕。该IGMS项目由MPS多学科活动办公室（OMA）和数学科学部（DMS）共同支持。