McNair/Gateway Scholars Program USC

Erin Lee

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Major and Classification

Biology and Spanish

Faculty Mentor

  • Michel Baudry, Ph.D.

Department

  • Neurobiology and Neuroscience

McNair Project

Progesterone Inhibits Estrogen-Mediated Neuroprotection Against Excitotoxicity by Down-Regulating Estrogen Receptor-?

Abstract
Alzheimer's Disease (AD) is more prevalent in women than in men, suggesting that the depletion of female steroid hormones, such as progesterone (P4) and estrogen, in post-menopausal women aggravates the risk of developing AD. Based on several in vitro and in vivo experiments on neurodegeneration, 17?-estradiol (E2) and progesterone (P4) have been found to be neuroprotective against a variety of insults. However, when E2 and P4 were combined, P4 generally reversed E2-mediated neuroprotection. Recent studies indicated that administering E2 for 20 h to cultured hippocampal slices and then adding P4 for 4 h eliminated the neuroprotective effects of E2 against NMDA toxicity. In this study, we examined the role of the two major subtypes of estrogen receptors, ER? and ER�, in E2-mediated neuroprotection against NMDA neurotoxicity in organotypic hippocampal slices. Treatment with E2 did not modify ER? mRNA and treatment with P4 reversed E2-induced increases in ER� mRNA and protein levels. However, P4 treatment reversed E2-mediated increase in ER? protein levels. Experiments with an ER? agonist, PPT, or an ER�-specific agonist, DPN, indicated that E2-mediated neuroprotection against NMDA toxicity was mediated by the activation of ER� but not of ER? receptors. Our results show that E2-mediated neuroprotection against NMDA toxicity is due to the activation of ER� receptors. Particularly, P4 treatment following E2 treatment results in the down-regulation of ER� mRNA and protein. The understanding of the underlying mechanisms of estrogen-progesterone interactions is important in order to yield a safe and effective treatment for postmenopausal women at risk for developing neurodegenerative diseases