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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.

Reported by

Pazmany Peter ut 1/c
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