Professor, Department of Pediatrics
Research in Dr. Anne Etgen's laboratory is focused on determining the cellular and molecular mechanisms by which ovarian steroid hormones regulate brain function. Investigations center on two topics:
1) how ovarian steroids act in neuroendocrine brain regions (e.g., hypothalamus and preoptic area) to coordinate female reproductive physiology and behavior, and
2) how estradiol and related estrogens promote neuronal survival after transient global ischemia
These two research questions are described in more detail below.
1) A major focus in the lab is the regulation of female reproductive physiology and behavior by the ovarian hormones, estradiol and progesterone. We wish to understand how hormonal modulation of synaptic transmission in specific brain regions coordinates the timing of ovulation with mating behavior (lordosis), thereby maximizing reproductive success. It is well known that estradiol acts via a ligand-activated transcription factor, estrogen receptor-á (ERá), to regulate female reproductive function. Recent findings from our lab indicate that hypothalamic insulin-like growth factor-1 (IGF-1) receptors act in concert with ERá to control gondatropin releasing hormone (GnRH) neurons and hence female reproductive function. We are now testing two related hypotheses: (1) that IGF-1 regulates estradiol-dependent afferent signals to GnRH neurons, and (2) that IGF-1 regulates GnRH neuronal responsiveness to afferent input. We are also working in collaboration with Genevieve Neal-Perry, M.D., Ph.D., to test the hypothesis that reduced IGF-1 receptor signaling in the aging brain may be responsible for attenuated neural responses to ovarian steroids and hence the delayed and attenuated luteinizing hormone (LH) surge that characterizes the perimenopause. Other experiments test the hypothesis that the delayed onset and reduced amplitude of the preovulatory LH surge in middle-aged female rats results from changes in the ability of ovarian steroids to modulate excitatory (glutamate and kisspeptin) and inhibitory (GABA) signals that regulate GnRH neurons. Recent findings suggest that intra-hypothalamic infusion of the neuropeptide kisspeptin, a potent activator of GnRH neurons, rescues LH surges in middle-aged females by enhancing local glutamate release.
2) A second major research topic in the Etgen laboratory is the role of estradiol and IGF-1 in improving outcomes after global ischemia (e.g., in cardiac arrest). This project is being carried out in collaboration with R. Suzanne Zukin. We have shown that physiological levels of estradiol reduce both hippocampal neuron loss and ischemia-induced cognitive impairments in young female rats. These neuroprotective actions of estradiol require co-signaling by brain IGF-1 receptors and are mediated by the ERK/MAPK signaling pathway. We are now investigating whether the middle-aged brain retains its responsiveness to the neuroprotective actions of estradiol and IGF-1, and if the duration of hormone withdrawal influences the efficacy of hormone treatment. Our findings suggest that both estradiol and IGF-1 can rescue hippocampal neurons from ischemia-induced cell death in middle-aged females even after a prolonged interval of estrogen deprivation.
Dr. Etgen is co-chair of the Professional Development Committee and chair of the Diversity in Neuroscience Subcommittee of the society for Neuroscience, and a member of the Society for the Study of Reproduction, International Brain Research Organization, and Society for Behavioral Neuroendocrinology.
Dr. Etgen completed her PhD in biological sciences with a specialty in neuroscience at the University of California, Irvine.
De Butte-Smith, M., Gulinello, M., Zukin, R.S., and Etgen A.M. (2009), Chronic estradiol treatment increases CA1 cell survival but does not improve visual or spatial working memory performance after global ischemia in middle-aged female rats. Horm. Behav. 55:442-453.
González-Flores, O., Gómora-Arrati, P., Garcia-Juárez, M., Gómez-Camarillo, M.A., Lima-Hernández, F.J., Beyer, C. and Etgen, A.M. (2009), Nitric oxide and MAPK mediation of estrous behavior induced by GnRH, PGE2 and db-cAMP in rats. Physiol. Behav. 96:606–612.
Neal-Perry, G.S., Lebesgue, D., Shu, J., Zeevalk, G.D., and Etgen, A.M. (2009), Kisspeptin restores the luteinizing hormone surge by modulating amino acid neurotransmission in the medial preoptic area of middle-aged female rats. Endocrinology 150:3699-3708.
Lebesgue, D., Chevaleyre, V., Zukin, R.S. and Etgen, A.M. (2009), Estradiol rescues neurons from global ischemia-induced cell death: Multiple cellular pathways of neuroprotection. Steroids 74:555-561.
Lebesgue, D., Reyna-Neyra, A., Huang, X., and Etgen, A.M. (2009), GPR30 differentially regulates short latency responses of luteinizing hormone and prolactin secretion to oestradiol. J. Neuroendocrinol. 21:743-752.
Etgen, A.M. and Garcia-Segura, L.M. (2009), Estrogen regulation of neurotransmitter and growth factor signaling in the brain. In: Hormones, Brain and Behavior, second edition (Ed. D.W. Pfaff, A.P. Arnold, A.M. Etgen, S.E. Fahrbach and R.T. Rubin), vol. 2, pp. 1121-1162. Academic Press/Elsevier Science USA, San Diego.
Etgen, A.M. and Pfaff, D.W. (2009), Historical and conceptual introduction to molecular forays intended to explain hormone/behavior relations. In: Molecular Mechanisms of Hormone Actions on Behavior (Ed. A.M. Etgen and D.W. Pfaff), pp. 1-4. Academic Press/Elsevier Science USA, San Diego.
Traub, M.L., De Butte-Smith, M., Zukin, R.Z. and Etgen, A.M. (2009). Oestradiol and insulin-like growth factor-1 reduce neuron loss after global ischemia in middle-aged female rats. J. Neuroendocrinology 21:1038-1044.
Lederman, M.A., Lebesgue, D., Gonzalez, V.V., Merhi, Z., Shu, J., Etgen, A.M. and Neal-Perry, G.S. (2010), Age-related LH surge dysfunction correlates with reduced responsiveness of hypothalamic anteroventral periventricular nucleus kisspeptin neurons to estradiol positive feedback in middle-aged rats. Neuropharmacology 58:314-320.
Todd, B.J., Merhi, Z.O., Shu, J., Etgen, A.M. and Neal-Perry, G.S. (2010), Hypothalamic insulin-like growth factor 1 receptors are necessary for hormone-dependent LH surges: Implications for female reproductive aging. Endocrinology 151:1356-1366.
Lebesgue, D., Traub, M., De Butte-Smith, M., Chen, C., Zukin, R.S., Kelly, M.J. and Etgen, A.M. (2010), Acute administration of non-classical estrogen receptor agonists attenuates ischemia-induced hippocampal neuron loss in middle-aged female rats. PLoSONE 5(1):e8642.
Jover-Mengual, T., Latuszek, A., Miyawaki, T., Alborch, E., Zukin, R.S. and Etgen, A.M. (2010), Acute estradiol protects CA1 neurons from ischemia-induced apoptotic cell death via the PI3K/Akt pathway. Brain Res. 1321:1-12.
Frugoli, J., Etgen, A.M., and Kuhar M. (2010), Developing and communicating responsible data management policies to trainees and colleagues. Science & Engineering Ethics 16:753–762.
González-Flores, O., Beyer, C., Gómora-Arrati, P., García-Juárez, M., Lima-Hernández, F.J., Soto, A., and Etgen, A.M. (2010), A role for Src kinase in progestin facilitation of estrous behavior in estradiol-primed female rats. Horm. Behav. 58(2):223-229.
Kabat, G.C., Etgen, A.M., and Rohan, T.E. (2010), Do steroid hormones play a role in the etiology of glioma? (minireview). Cancer Epidemiology, Biomarkers & Prevention 19(10):2421-2427.
Etgen, A.M., Jover-Mengual, T., and Zukin, R.S. (2011), Neuroprotective actions of estradiol and novel estrogen analogs in ischemia: Translational implications. Frontiers in Neuroendocrinology 32:336-352.
García-Juárez, M., Beyer, C., Soto-Sánchez, A., Domínguez-Ordoñez, R., Gómora-Arrati, P., Eguibar, J.R., Etgen, A.M., and González-Flores, O. (2011). Leptin facilitates lordosis behavior through GnRH-1 and progestin receptors in estrogen-primed rats. Neuropeptides 45(1):63-67.
Sun, Y., Todd, B.J., Thornton, K., Etgen, A.M. and Neal-Perry, G.S. (2011), Differential effects of hypothalamic insulin-like growth factor-1 receptors on gonadotropin releasing hormone neuronal activation during steroid-induced LH surges in young and middle-aged female rats. Endocrinology, in press.
More Information About Dr. Anne Etgen
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Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Forchheimer Building, Room 113
Bronx, NY 10461