February 19, 2015

Erin Lee

lee.erinMajor 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