RAPIDESTROGEN · Definition of signaling pathways mediating rapid actions of estrogen in specific neuronal phenotypes
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2004-11-01 → 2005-10-31
- EU contribution
- €40,000
- Participants
- 1
- Scheme
- ERG
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Results in brief
Final Activity Report Summary - RAPIDESTROGEN (Definition of signaling pathways mediating rapid actions of estrogen in specific neuronal phenotypes)
Oestrogen secreted from the ovaries regulates the function of the reproductive axis (hypothalamus, pituitary, ovary, and other reproductive organs) and also exerts powerful modulatory effects on cognitive processes. Although oestrogen is known to have effects on gene transcription via classical oestrogen receptors, it has recently become clear that it also exerts rapid effects on neurons by altering second messenger transduction pathways such as ERK1/2, calcium and cAMP. In turn, these non-classical effects can impinge upon transcription by altering the phosphorylation status of key transcription factors such as cAMP response element-binding protein (CREB). As a consequence, these ill-defined non-classical, rapid actions of oestrogen could have a critical role in control brain functions. We demonstrated that oestrogen play critical role in the oestrogen induced rapid action on ERK1/2 phosphorylation in the brain in vivo. Additionally, we disclosed that rapid actions of oestrogen in principal neurons of the reproductive axis, the Gonadotropin-releasing hormone (GnRH) neurons, require the presence of ERK1/2 for CREB phosphorylation. In addition, we have showed the oestrogen also has rapid action in cholinergic neurons. These neurons play important role in memory formation and they are highly affected in Alzheimer disease. Using a multidisciplinary approach involving electrophysiological, immunohistochemical, confocal imaging, molecular biological and transgenic techniques our work provides solid basis for understanding the mechanisms of non-classical oestrogen actions upon the GnRH and cholinergic neurons. This work also provided critical scientific information underpinning the future treatment of infertility and age-related dementia within Europe.
Data: CORDIS, © European Union
Project objective
Estrogen secreted from the ovaries regulates the function of the reproductive axis (hypothalamus, pituitary ovary, and other reproductive organs) and also exerts powerful modulatory effects on cognitive processes Although estrogen is known to have effects on gene transcription via classical estrogen receptors, it has recently become clear that it also exerts rapid effects on neurons by altering second messenger transduction pathway such as calcium and cAMP.In turn, these rapid effects can impinge upon transcription by altering the phosphorylation status of key transcription factors such as cAMP response element-binding protein (CREB). As a consequence, these ill-defined nongenomic" actions of estrogen are now thought to have a critical role in estrogen-dependent brain functions. As a Marie Curie Research Fellow working in Cambridge, UK, I have recently demonstrated that rapid action of estrogen upon the principal neurons of the reproductive axis, the gonadotropin-releasing hormone (GnRH) neurons, require the presence of the classical estrogen receptor, ERp in vivo. This novel result was the first demonstration that ERp is involved in rapid estrogen actions. Based on this finding, I intend to continue my research in Hungary with the aim to characterize the rapid estrogen-sensitive signalling systems that exist ii GnRH neurons.I will also extend the work to evaluate possible rapid estrogen actions upon the basal forebrain cholinergic neurons that are involved in age-related dementia thought to be preventable by e strogen treatment. Using a multidisciplinary approach involving immunohistochemical, confocal imaging, molecular biological and transgenic techniques, my work will provide insights into the mechanisms of rapid estrogen actions upon the GnRH and cholinergic neurons. This will provide critical basic scientific information underpinning the future treatment of infertility and age-related dementia within Europe."
Original text from CORDIS.
Participants
- EOETVOES LORAND UNIVERSITY · BUDAPESTCoordinatorCity levelHungary
Links
Data: CORDIS, © European Union