[Effects of estrogens on the brain and implications for neuro-protection]

Numerous biological effects of oestrogens within the brain support the argument that their influence is not restricted to the reproductive system. Specific estrogen receptors were found in the central nervous system as early as in the 70's, but until recently little was known about the molecular background of oestrogens activity in the brain. The last decade witnessed a great effort aimed at better understanding of the tangled molecular mechanisms underlying subtle liaisons between brain metabolism and cerebral blood flow and particularly their disturbances triggered by brain ischaemia. These investigations had an ultimate goal--an effective method of preventing an expanding biochemical "catastrophe" within and around the ischaemic brain regions (the so-called "neuroprotection"). Molecular mechanisms by which oestrogens increase both metabolism and blood flow through certain regions of the brain became only recently better understood. Now there is a consensus as to that these hormones increase secretion of neuromediators, stimulate formation of new synapses and can activate certain genes, responsible for production of anti-apoptotic proteins and growth factors. Oestrogens can also dilate cerebral vessels, here acting through increased synthesis of nitric oxide and by stimulating such compounds as prostacycline and a potent vasodilator-epoxyeikosotrienoic acid. There is a body of recent evidence which suggest that during brain ischaemia the physiological estrogen stimulation, of both, brain metabolism and cerebral blood flow, becomes biased towards increased release of vasodilating substances. As the metabolism is not spurred accordingly, the net effect of oestrogens is neuroprotection. Other protective properties of oestrogens within the brain are related to attenuation of the excitotoxic effects of glutamate and to the activation of enzymes scavenging free oxygen radicals. Moreover, oestrogens can diminish free radicals synthesis and act as free radicals scavengers themselves. They can also activate synthesis of bcl-2 protein, which prevents cell apoptosis in the ischaemic regions. The relevant evidence, which continue to accumulate, may suggest that it is time now to consider launching a clinical investigation on the role of oestrogens as potentially important neuroprotective factors.