Global Synchrony and Frequency Modulation in the Anterior Pituitary

尽管经过了20年的深入生物学和医学研究，但循环中的雌二醇如何启动脑下垂体黄体生成素(LH)的激增，从而引发排卵，其机制仍然是人类生理学中的一个谜。PI和她的合作者开发的瞬时共振模型是第一个关于黄体生成素激增的数学模型，它将多个时间尺度上的实验数据与治疗卡尔曼综合征等不孕症所需的令人惊讶的激素替代脉冲频率特性统一起来。该模型预测，脑下垂体有一种取决于循环类固醇水平的内在节律，而脑垂体对脉动性下丘脑刺激的反应取决于下丘脑和脑下垂体节律之间的频率相互作用。私家侦探将在康奈尔大学神经生物学和行为系的麦考布实验室工作一年。目标是：(1)学习实验神经科学的语言和基本技术。(2)在不同的激素环境下对模型预测进行实验验证。(3)收集初步数据，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(整体)研究该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。了解下丘脑和脑下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，这些包括卵巢癌和乳腺癌、更年期、激素替代疗法、不孕症诊断和治疗以及避孕。这项IGMS项目由MPS多学科活动办公室(OMA)和数学科学部(DMS)联合支持。

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).