Stressful events cause short- and long-term changes in body functions and behavior to suppress those that are not critical for immediate survival and promote those that are. Stress coping is an important adaptive mechanism in allowing the organism to quickly adapt to challenging circumstances that threaten survival. Stress influences various organs of organisms, including especially the brain, to affect processes related to homeostasis, cognition, immune function, reproduction, and fight-or-flight behavioral responses. Interestingly, sex differences in stress reactivity have been observed, with females usually exhibiting higher reactivity to a stressor than males. Furthermore, it has also been demonstrated that estrogens enhance stress reactivity while androgens inhibit it. Important to this project are recent findings from the PI's laboratory that estrogen effects on stress and anxiety are mediated by the protein estrogen receptor beta (ER-beta) expressed in the brain. The working hypothesis is that activation of ER-beta within distinct brain regions is critical for modulation of stress-reactivity, which then impacts the stress circuitry throughout the body. This EAGER project will create a unique model in which the protein ER-beta can be manipulated in a specific cell type and/or at a chosen time in targeted regions of the brain while still allowing the expression of this key signaling protein in other tissues. This model system will be utilized to study the role of ER-beta in producing sex differences in stress reactivity not only in the brain, but also to better understand how stress affects the organism at the general physiological and behavioral levels. The findings will impact not only understanding of the neuroendocrine regulation of stress, but also the areas of developmental biology, reproductive biology, cognitive neuroscience, and the evolution of sex differences. The project will provide training experience for students and fellows in a hybrid area that integrates molecular techniques with physiology using a comprehensive approach and unique model systems. The goal is to involve the trainees in all aspects of scientific research including advanced technical approaches in molecular biology and genomics, data interpretation and analysis, research ethics, presentation of data at national meetings, and publication of their findings.
