By Novartis Foundation, Novartis Foundation Symposium
Even though commonly considered a intercourse hormone, contemporary learn has highlighted the varied and important results that oestrogen has at the CNS, extending a long way past its very important reproductive position. it's been proven that oestrogen acts as a neural development issue with vital impacts at the survival, plasticity, regeneration and growing older of the mammalian brain.
This intriguing booklet 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 capabilities in animals and people. eventually, fresh examine at the function of oestrogens in getting old and dementia, together with the importance of oestrogen motion in Alzheimer's illness, is mentioned. The 15 papers contained during this publication, including the large dialogue periods that stick to them, display a lot new and intriguing paintings during this quarter, and determine promising new examine instructions.
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Extra info for Neuronal and Cognitive Effects of Oestrogens (Novartis Foundation Symposium 230)
Sample text
McEwen: Donald Pfa¡, you commented earlier that there is expression of ERb message in places like the cerebellum and the hippocampus, where there is sparse evidence at this point for any kind of high a⁄nity oestrogen binding, and the jury is still out on protein expression. You implied that there may even be a ligandindependent expression of a protein that can have some kind of regulatory function. Could you say more on this? Pfa¡: I said this because when we looked at the cognitive performance of ER knockout (ERKO) animals, in the absence of either ovaries or testes, there’s a di¡erence in the decline of incorrect responses between ERKO and wild-type (S.
Kushner: It’s certainly possible. Rosalie Uht in my lab has been studying the interaction of glucocorticoid receptors and ERs at these AP-1 sites. The glucocorticoid receptor is known to repress, while the ER activates. We looked at what happens if both are present, in competition. It turns out that the most abundant receptor wins out. It is possible to block ER action with enough OESTROGEN RECEPTOR FUNCTION AT EREs 29 glucocorticoid receptor, and then this repression can be relieved by increasing ER.
But there might be ligands so far undiscovered that ¢t in the ligand-binding pocket of ERb2. This is a fascinating possibility. Toran-Allerand: At very high doses, genistein acts as a receptor tyrosine kinase inhibitor, and if one were to take huge amounts of it, one might ¢nd oneself in a lot of trouble. Simpkins: In hippocampus, cortex or cerebellum, what percentage of neurons show positive binding for either ER? Gustafsson: ERb is more widely distributed than ERa. As a rough ¢gure, I’d say that 20% of the total neurons would be ERa or ERb positive.