Major and Classification
Biology and Spanish
- Michel Baudry, Ph.D.
- Neurobiology and Neuroscience
The Mechanism of Estrogen-Progesterone Interactions Unraveled
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