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Definition of signaling pathways mediating rapid actions of estrogen in specific neuronal phenotypes

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.

Field of science

  • /natural sciences/chemical sciences/inorganic chemistry/inorganic compounds

Call for proposal

FP6-2002-MOBILITY-11
See other projects for this call

Funding Scheme

ERG - Marie Curie actions-European Re-integration Grants

Coordinator

EOETVOES LORAND UNIVERSITY
Address
Egyetem T¿1-3
Budapest
Hungary