Neuronal and Cognitive Effects of Oestrogens: Novartis by Novartis Foundation, Novartis Foundation Symposium

By Novartis Foundation, Novartis Foundation Symposium

Even supposing in most cases regarded as a intercourse hormone, contemporary examine has highlighted the varied and critical results that oestrogen has at the CNS, extending a ways past its vital reproductive position. it's been proven that oestrogen acts as a neural progress issue with very important impacts at the survival, plasticity, regeneration and ageing of the mammalian brain.

This intriguing ebook brings jointly top clinicians and researchers to debate oestrogen's simple mechanisms of motion, the extrahypothalmic mind areas it impacts, and its impact on cognitive services in animals and people. ultimately, contemporary examine at the function of oestrogens in growing old and dementia, together with the importance of oestrogen motion in Alzheimer's disorder, is mentioned. The 15 papers contained during this e-book, including the large dialogue periods that stick with them, demonstrate a lot new and fascinating paintings during this sector, and determine promising new learn directions.Content:

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When oestrogen, which has worked its way to the nucleus binds the receptor, the ER dissociates from the heat shock protein complex, dimerizes and binds to EREs. Once bound to the ERE, the ER uses AF-1 and AF-2 to stimulate transcription from the promoter. Recent studies reveal that AF-1 (Webb et al 1998, Tremblay et al 1999) and AF-2 (Xu et al 1999) work by binding to coactivators of the p160 family, which has three members SRC-1, GRIP1 and p/CIP. These proteins bind the ER LBD very tightly in the presence of oestrogen.

We picked that site because previous studies with the glucocorticoid receptor had shown that the site which is conserved in all nuclear receptors changed the behaviour of receptors on AP-1. The glucocorticoid receptor normally inhibits AP-1 target chains. If you make the analogous mutation K461A, it becomes an activator. Since the ER was an activator, we decided to look to see what would happen. This is puzzling because it is in the DBD. We know that the mutation does not increase the ability of the receptor to activate at the classical response pathway; it only has an e¡ect at this AP-1 pathway.

Levin Division of Endocrinology, Veterans A¡airs Medical Center, Long Beach, Long Beach, CA 90822 and Departments of Medicine and Pharmacology, University of California, Irvine, Irvine CA 92717, USA Abstract. The co-existence of both plasma membrane and nuclear oestrogen receptors has changed our thinking about the mechanisms of the actions of this sex steroid. To date, however, the plasma membrane receptor has not been isolated. However, many emerging data implicate this receptor in the rapid, non-genomic e¡ects of oestrogen, and this is seen when the membrane receptor e¡ects a variety of signal transduction events.

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