Progesterone inhibits estrogen-mediated neuroprotection against excitotoxicity by down-regulating estrogen receptor-beta.

Article Details

Citation

Copy to clipboard

Aguirre C, Jayaraman A, Pike C, Baudry M

Progesterone inhibits estrogen-mediated neuroprotection against excitotoxicity by down-regulating estrogen receptor-beta.

J Neurochem. 2010 Dec;115(5):1277-87. doi: 10.1111/j.1471-4159.2010.07038.x. Epub 2010 Oct 26.

PubMed ID

20977477 [ View in PubMed

]

Abstract

While both 17beta-estradiol (E2) and progesterone (P4) are neuroprotective in several experimental paradigms, P4 also counteracts E2 neuroprotective effects. We recently reported that a 4-h treatment of cultured hippocampal slices with P4 following a prolonged (20 h) treatment with E2 eliminated estrogenic neuroprotection against NMDA toxicity and induction of brain-derived neurotrophic factor (BDNF) expression. In the present study, we evaluated the effects of the same treatment on levels of estrogen receptors, ERalpha and ERbeta, and BDNF using a similar paradigm. E2 treatment resulted in elevated ERbeta mRNA and protein levels, did not modify ERalpha mRNA, but increased ERalpha protein levels, and increased BDNF mRNA levels. P4 reversed E2-elicited increases in ERbeta mRNA and protein levels, in ERalpha protein levels, and in BDNF mRNA levels. Experiments with an ERbeta-specific antagonist, PHTPP, and specific agonists of ERalpha and ERbeta, propylpyrazoletriol and diarylpropionitrile, respectively, indicated that E2-mediated neuroprotection against NMDA toxicity was, at least in part, mediated via ERbeta receptor. In support of this conclusion, E2 did not protect against NMDA toxicity in cultured hippocampal slices from ERbeta-/- mice. Thus, E2-mediated neuroprotection against NMDA toxicity may be because of estrogenic induction of BDNF via its ERbeta receptor, and P4-mediated inhibition of E2 neuroprotective effects treatment to P4-induced down-regulation of ERbeta and BDNF.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Progesterone	Estrogen receptor beta	Protein	Humans	Unknown	Agonist Downregulator	Details