Areas of Interest
The overall goal of our laboratory's research is to understand the central neuronal processes underlying reproduction. Work focuses on determining how gonadotropin-releasing hormone (GnRH) neurons produce the episodic release of GnRH required for fertility, as well as to understand the role of GnRH in 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 release of gonadotropic hormones by the pituitary gland. Further, the frequency of GnRH release changes throughout the female reproductive cycle and these changes are prerequisite for shifting the relative levels of the two gonadotropins to allow for ovarian follicular development and maturation. 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 is often referred 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 as a result of 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 are investigating 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 a hope of someday transferring this knowledge to clinical care
Published Articles or Reviews
- Silveira MA, Burger LL, DeFazio RA, Wagenmaker ER, Moenter SM 2017 GnRH neuron activity and pituitary response in estradiol-induced vs proestrous luteinizing hormone surges in female mice. Endocrinology 158:356-366. PMC5413083
- Wagenmaker ER, Moenter SM 2017 Exposure to acute psychosocial stress disrupts the luteinizing hormone surge independent of estrous cycle alterations in female mice. Endocrinology, 158: 2593-2602, PMC5551545
- Vanacker C, Ricu MR, DeFazio RA, Johnson ML, Moenter SM 2017 Long-term recordings of arcuate nucleus kisspeptin neurons reveal patterned activity that is modulated by gonadal steroids in male mice. Endocrinology 158:3553-3564, PMC5659697
- Dulka EA, Moenter SM 2017 Prepubertal development of gonadotropin-releasing hormone (GnRH) neuron activity is altered by sex, age and prenatal androgen exposure. Endocrinology 158: 3943–3953, PMC5695838
- Phumsatitpong C, Moenter SM 2018 Estradiol-dependent stimulation and suppression of gonadotropin-releasing hormone (GnRH) neuron firing activity by corticotropin-releasing hormone (CRH) in female mice. Endocrinology 159:414–425, PMC5761586
- Wang L, Burger LL, Greenwald-Yarnell ML, Myers MG, Moenter SM 2018 Glutamatergic transmission to hypothalamic kisspeptin neurons is differentially regulated by estradiol through estrogen receptor α in adult female mice. J Neurosci 38:1061-1072, PMC5792470
- Adams CE, Stroberg W, DeFazio RA, Schnell S, Moenter SM 2018Gonadotropin-releasing hormone (GnRH) neuron excitability is regulated by estradiol feedback and kisspeptin. J Neuroscience 38:1249-1263, PMC5695838.
- Berg T, Silveira MA, Moenter SM 2018 Prepubertal development of GABAergic transmission to gonadotropin-releasing hormone (GnRH) neurons and postsynaptic response are altered by prenatal androgenization. J Neurosci, 38:2283-2293, PMC5830516
- Burger LL, Vanacker C, Phumsatitispong C, Wagenmaker ER, Wang L, Olson DP, Moenter SM 2018 Identification of genes enriched in GnRH neurons by translating ribosome affinity purification and RNASeq in mice. Endocrinology, 159:1922-1940, PMC6287592
- Adams C, Chen X, Moenter SM 2018 Changes in GABAergic transmission to and intrinsic excitability of gonadotropin-releasing hormone (GnRH) neurons during the estrous cycle in mice. eNeuro. 2018 Nov 8;5(5). pii: ENEURO.0171-18.2018. doi: 10.1523/ENEURO.0171-18.2018. PMC6223108
- Adams C, DeFazio RA, Christian CA, Milescu LS, Schnell S, Moenter SM 2019 Changes in both neuron intrinsic properties and neurotransmission are needed to drive the increase in GnRH neuron firing rate during estradiol-positive feedback. J Neurosci 39:2091-2101. doi: 10.1523/JNEUROSCI.2880-18.2019. PMC in process
- Wang,L, Vanacker C, Burger LL, Barnes T, Shah YM, Myers MG, Moenter SM 2019 Genetic dissection of the different roles of hypothalamic kisspeptin neurons in regulating female reproduction. Elife. 2019 Apr 4;8. pii: e43999. doi: 10.7554/eLife.43999. PMC6491090