Montana Bruckner, “Effects of a Novel Estrogen Receptor Beta Agonist on Memory and Hot Flashes Related to Menopause”
Mentor: Karyn Frick, Psychology, Letters & Science (College of)
Poster #111
Menopausal symptoms such as hot flashes and memory loss create difficulty in daily function for older women. Although hormone therapy including estrogens can alleviate many menopausal symptoms, treatment can increase risks of cancer due to the binding of estrogens to a protein called estrogen receptor (ERɑ) . In contrast, the other major estrogen receptor, called estrogen receptor𝛽 (ERꞵ), reduces risk of cancer. Therefore, our lab has spent the past few years developing very highly selective new ERꞵ agonist drugs to improve memory and reduce hot flashes without cancer-causing side effects. Our latest compound, called EGX999, is 1,200-fold more selective for ERꞵ over ERɑ, but we have yet to test its effects on menopausal symptoms. The goal of the present study is to determine the extent to which long-term oral treatment with EGX999 can promote memory formation and reduce hot flash-like symptoms in a mouse model of menopause. Ovariectomized female mice consume a gel-like substance that contains vehicle (control), the potent estrogen 17𝛽-estradiol (E2), a low dose (3 mg/kg/day) of EGX999, or a high dose (30 mg/kg/day) of EGX999. After weeks of treatment, memory was tested in object recognition and object placement tasks. Hot flashes were induced by injection of senktide, a neurokinin-3 receptor agonist that causes vasodilation similar to a hot flash. This vasodilation is measured by infrared imaging of tail skin temperature because mice release heat via tails. Our lab has previously shown that EGX358, a less selective ERꞵ agonist, enhances memory in both tasks and reduces the magnitude of the senktide-induced hot flash. We expect that the more selective ERꞵ agonist EGX999 may be a better alternative that previously tested EGX358 in reducing menopause-related symptoms. Results are currently being analyzed and will be discussed. Further testing could bring improved medications for menopausal symptom relief.