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).
