Areas of Interest
The overall goal of our laboratory's research is to understand the central neuronal processes underlying reproduction. Our work focuses on determining how gonadotropin-releasing hormone (GnRH) neurons produce the episodic release of GnRH required for fertility and understanding the role of GnRH in the presentation of various forms of hypothalamic infertility. GnRH neurons form the final common pathway for the central regulation of reproduction in all vertebrates. GnRH is released in a pulsatile pattern that is critical for releasing gonadotropic hormones by the pituitary gland. Further, the frequency of GnRH release changes throughout the female reproductive cycle. These changes are prerequisites for shifting the relative levels of the two gonadotropins to allow for ovarian follicular development and maturation. The persistence of high-frequency GnRH release that is not frequency modulated is a hallmark of polycystic ovary syndrome (PCOS). PCOS affects approximately 8% of women and is a major cause of infertility and other health problems. Despite their importance, the mechanisms underlying episodic GnRH release are not well understood. This phenomenon refers to as the "GnRH-pulse generator". To study this pulse generator, we use transgenic mouse models in which the jellyfish reporter green fluorescent protein (GFP) is genetically targeted to GnRH and their afferent neurons. These mice enable us to identify living neurons and study them using electrophysiological, imaging, and molecular approaches.
Our research focuses on four themes. First, we want to understand the basic electrophysiological properties of GnRH neurons and how these change developmentally throughout the reproductive cycle and due to the reproductive state. This includes determining if rhythmicity is an intrinsic property of these cells or emerges as a network property, understanding the biophysical events underlying rhythm generation, and studying how GnRH neurons communicate to produce synchronous hormone release. Second, we are examining the physiological feedback effects of gonadal steroids to understand how these steroids alter the basic properties of GnRH neurons and their afferents to bring about changes in GnRH release. Third, we investigate the mechanisms by which psychosocial stress inhibits GnRH neurons and thus fertility. Finally, we have generated models that reproduce some of the symptoms of PCOS and are conducting experiments to understand how the function of GnRH neurons is hyperactivated in this disease state and to provide models for reversing this phenomenon with the hope of someday transferring this knowledge to clinical care.
- McCartney CR, Campbell RE, Marshall JC, Moenter SM 2022The role of gonadotropin-releasing hormone neurons in polycystic ovary syndrome. J Neuroendocrinology e13093, https://doi.org/10.1111/jne.13093
- Han X, Burger LL, Garcia Galiano D, Moenter SM, Myers MG, Olson DP, Elias CF 2021 Protocol to extract actively translated mRNAs from mouse hypothalamus by translating ribosome affinity purification. STAR Protocols 2, 100589, June 18, 2021. PMC8196219
- DeFazio RA, Moenter SM 2021 Lack of sex differences in gonadotropin-releasing hormone (GnRH) neuron potassium currents and excitability. 2021 Jul 7;8(4):ENEURO.0126-21.2021 BIORXIV/2021/03/24/436851, PMC8266219
- Vanacker CMH, DeFazio RA, Sykes CM, Moenter SM 2021 A role for glial fibrillary acidic protein (GFAP)-expressing cells in the regulation of gonadotropin-releasing hormone (GnRH) but not arcuate kisspeptin neuron output. Jul 22;10:e68205. doi: 10.7554/eLife.68205. BIORXIV/2021/434805, PMC8337074