- Assistant Professor, Department of Obstetrics and Gynecology, Committee on Molecular Medicine/MPMM, Committee on Molecular Metabolism and Nutrition
- Director, In Vitro Fertilization
M.D. Cornell University, 1991
The University of Chicago
5841 South Maryland Avenue
Chicago, Illinois 60637
Phone: (773) 702-6642
Molecular Mechanisms Involved in the Regulation of the Mouse Gonadotropin-releasing Hormone (mGnRH) Gene.
Since July 1998, I have been investigating the molecular mechanisms involved in the regulation of the mouse Gonadotropin-releasing Hormone (mGnRH) gene. It has been estimated that only 1000 neurons express GnRH. Initially, I sought to identify the factors that permit GnRH expression in these neurons. Because in vitro studies do not reflect the intricacy of in vivo GnRH gene regulation, I constructed transgenic mice containing different promoter fragments of the mGnRH gene fused to the luciferase reporter gene. With luciferase expression under the control of the mGnRH promoter, mGnRH gene expression can be detected easily by measuring the luciferase activity in tissue homogenates.
Examination of the mGnRH-luciferase mice revealed another area of investigation. Extremely high levels of luciferase expression were detected in the ovaries collected from mice containing a deletion in the distal part of the mGnRH promoter. The mice bearing the full-length GnRH promoter had minimal ovarian expression, suggesting that sequences in the distal part of the mGnRH promoter mediate repression of mGnRH expression in the ovary.
These mGnRH-luciferase mice provide a powerful tool for examining the regulation of mGnRH expression in vivo. Using these mGnRH-luciferase transgenic mice, I have identified a region of the mGnRH promoter that targets mGnRH expression to the hypothalamus and also defined an ovarian GnRH repressor element in the distal mGnRH promoter region. By characterizing these promoter regions, I will identify transcription factors that regulate mGnRH expression. Eventually, I hope to reveal the mechanisms by which neuronal and ovarian GnRH are differentially regulated.