The Experts below are selected from a list of 16116 Experts worldwide ranked by ideXlab platform
Eric R Prossnitz - One of the best experts on this subject based on the ideXlab platform.
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gper gpr30 knockout mice effects of gper on metabolism
Methods of Molecular Biology, 2016Co-Authors: Geetanjali Sharma, Eric R ProssnitzAbstract:: Endogenous Estrogens, predominantly 17β-estradiol (E2), mediate various diverse effects throughout the body in both normal physiology and disease. Actions include development (including puberty) and reproduction as well as additional effects throughout life in the metabolic, endocrine, musculoskeletal, nervous, cardiovascular, and immune systems. The actions of E2 have traditionally been attributed to the classical Nuclear Estrogen receptors (ERα and ERβ) that largely mediate transcriptional/genomic activities. However, more recently the G protein-coupled Estrogen receptor GPER/GPR30 has become recognized as an essential mediator of certain, and particularly rapid, signaling events in response to E2. Murine genetic knockout (KO) models represent an important approach to understand the mechanisms of E2 action in physiology and disease. Studies of GPER KO mice over the last years have revealed functions for GPER in the regulation of obesity, insulin resistance and glucose intolerance, among other areas of (patho)physiology. This chapter focuses on methods for the evaluation of metabolic parameters in vivo and ex vivo with an emphasis on glucose homeostasis and metabolism through the use of glucose and insulin tolerance tests, pancreatic islet and adipocyte isolation and characterization.
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the g protein coupled Estrogen receptor gper in health and disease
Nature Reviews Endocrinology, 2011Co-Authors: Eric R Prossnitz, Matthias BartonAbstract:Estrogens regulate physiological and pathological processes in both women and men. Traditionally, the actions of 17β-estradiol, the predominant and most potent endogenous Estrogen, were ascribed to two Nuclear Estrogen receptors (ERs), ERα and ERβ; however, transmembrane ERs, such as G-protein-coupled ER 1 (GPER), have been implicated in rapid Estrogen signaling. This Review provides an overview of Estrogen signaling and its receptors, with particular emphasis on GPER. It also highlights the importance of GPER in health and disease, such as cancer, for which GPER is a potential therapeutic target and prognostic indicator.
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beneficial role of the gpr30 agonist g 1 in an animal model of multiple sclerosis
Journal of Neuroimmunology, 2009Co-Authors: Eric Blasko, Megan K Dennis, Eric R Prossnitz, Christopher A Haskell, Stewart Leung, Giovanna Gualtieri, Meredith Halksmiller, Mithra Mahmoudi, William J Karpus, Richard HorukAbstract:The beneficial effects of Estrogens in multiple sclerosis are thought to be mediated exclusively by the classical Nuclear Estrogen receptors ERalpha and ERbeta. However, recently many reports revealed that Estrogens are able to mediate rapid signals through a G protein-coupled receptor (GPCR), known as GPR30. In the present study, we set out to explore whether effects mediated through this receptor were anti-inflammatory and could account for some of the beneficial effects of Estrogen. We demonstrate that GPR30 is expressed in both human and mouse immune cells. Furthermore a GPR30-selective agonist, G-1, previously described by us, inhibits the production of lipopolysaccharide (LPS)-induced cytokines such as TNF-alpha and IL-6 in a dose-dependent manner in human primary macrophages and in a murine macrophage cell line. These effects are likely mediated solely through the Estrogen-specific receptor GPR30 since the agonist G-1 displayed an IC(50) far greater than 10 microM on the classical Nuclear Estrogen receptors as well as a panel of 25 other GPCRs. Finally, we show that the agonist G-1 is able to reduce the severity of disease in both active and passive EAE models of multiple sclerosis in SJL mice and that this effect is concomitant with a G-1-mediated decrease in proinflammatory cytokines, including IFN-gamma and IL-17, in immune cells harvested from these mice. The effect of G-1 appears indirect, as the GPR30 agonist did not directly influence IFN-gamma or IL-17 production by purified T cells. These data indicate that G-1 may represent a novel therapeutic agent for the treatment of chronic autoimmune, inflammatory diseases.
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beneficial role of the gpr30 agonist g 1 in an animal model of multiple sclerosis
Journal of Neuroimmunology, 2009Co-Authors: Eric Blasko, Megan K Dennis, Eric R Prossnitz, Christopher A Haskell, Stewart Leung, Giovanna Gualtieri, Meredith Halksmiller, Mithra Mahmoudi, William J Karpus, Richard HorukAbstract:The beneficial effects of Estrogens in multiple sclerosis are thought to be mediated exclusively by the classical Nuclear Estrogen receptors ERα and ERβ. However, recently many reports revealed that Estrogens are able to mediate rapid signals through a G protein-coupled receptor (GPCR), known as GPR30. In the present study, we set out to explore whether effects mediated through this receptor were anti-inflammatory and could account for some of the beneficial effects of Estrogen. We demonstrate that GPR30 is expressed in both human and mouse immune cells. Furthermore a GPR30-selective agonist, G-1, previously described by us, inhibits the production of lipopolysaccharide (LPS)-induced cytokines such as TNF-α and IL-6 in a dose-dependent manner in human primary macrophages and in a murine macrophage cell line. These effects are likely mediated solely through the Estrogen-specific receptor GPR30 since the agonist G-1 displayed an IC50 far greater than 10 μM on the classical Nuclear Estrogen receptors as well as a panel of 25 other GPCRs. Finally, we show that the agonist G-1 is able to reduce the severity of disease in both active and passive EAE models of multiple sclerosis in SJL mice and that this effect is concomitant with a G-1-mediated decrease in proinflammatory cytokines, including IFN-γ and IL-17, in immune cells harvested from these mice. The effect of G-1 appears indirect, as the GPR30 agonist did not directly influence IFN-γ or IL-17 production by purified T cells. These data indicate that G-1 may represent a novel therapeutic agent for the treatment of chronic autoimmune, inflammatory diseases.
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mechanisms of Estrogen signaling and gene expression via gpr30
Molecular and Cellular Endocrinology, 2009Co-Authors: Eric R Prossnitz, Marcello MaggioliniAbstract:The effects of Estrogen are widespread throughout the body. Although the classical Nuclear Estrogen receptors have been known for many years to decades and their primary modes of action as transcriptional regulators is well understood, certain aspects of Estrogen biology remain inconsistent with the mechanisms of action of these receptor. More recently, the G protein-coupled receptor, GPR30/GPER, has been suggested to contribute to some of the cellular and physiological effects of Estrogen. Not only does GPR30 mediate some of the rapid signal transduction events following cell stimulation, such as calcium mobilization and kinase activation, it also appears to regulate rapid transcriptional activation of genes such as c-fos. Since many cells and tissues co-express classical Estrogen receptors and GPR30, there exists great diversity in the possible avenues of synergism and antagonism. In this review, we will provide an overview of GPR30 function, focusing on the rapid signaling events that culminate in the transcriptional activation of certain genes.
Paul J Davis - One of the best experts on this subject based on the ideXlab platform.
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thyroid hormone causes mitogen activated protein kinase dependent phosphorylation of the Nuclear Estrogen receptor
Endocrinology, 2004Co-Authors: Hengyuan Tang, Shenli Zhang, Faith B Davis, Hungyun Lin, Paul J DavisAbstract:Activated by thyroid hormone, the MAPK (ERK1/2) signaling pathway causes serine phosphorylation by MAPK of several nucleoproteins, including the Nuclear thyroid hormone receptor beta1. Because Estrogen can activate MAPK and cause MAPK-dependent serine phosphorylation of Nuclear Estrogen receptor (ER)alpha, we studied whether thyroid hormone also promoted MAPK-mediated ERalpha phosphorylation. Human breast cancer (MCF-7) cells were incubated with physiological concentrations of l-T(4) or 17beta-estradiol (E(2)) for 15 min to 24 h, and Nuclear ERalpha and serine-118-phosphorylated ERalpha were identified by Western blotting. Serine-118-phosphorylated ERalpha was recovered at 15 min in nuclei of MCF-7 cells exposed to either T(4) or E(2). The T(4) effect was apparent at 15 min and peaked at 2 h, whereas the E(2) effect was maximal at 4-6 h. T(4)-agarose was as effective as T(4) in causing phosphorylation of ERalpha. T(4) action on ERalpha was inhibited by PD 98059, an inhibitor of ERK1/2 phosphorylation, and by tetraiodothyroacetic acid, a T(4) analog that blocks cell surface-initiated actions of T(4) but is not itself an agonist. Electrophoretic mobility shift assay of Nuclear extracts from T(4)-treated and E(2)-treated cells showed similar specific protein-DNA-binding. Indexed by [(3)H]thymidine incorporation and Nuclear proliferating cell Nuclear antigen, MCF-7 cell proliferation was stimulated by T(4) and T(4)-agarose to an extent comparable with the effect of E(2). This T(4) effect was blocked by either PD 98059 or ICI 182,780, an ER antagonist. Thus, T(4), like E(2), causes phosphorylation by MAPK of Nuclear ERalpha at serine-118 in MCF-7 cells and promotes cell proliferation through the ER by a MAPK-dependent pathway.
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thyroid hormone causes mitogen activated protein kinase dependent phosphorylation of the Nuclear Estrogen receptor
Endocrinology, 2004Co-Authors: Hengyuan Tang, Shenli Zhang, Faith B Davis, Paul J DavisAbstract:Activated by thyroid hormone, the MAPK (ERK1/2) signaling pathway causes serine phosphorylation by MAPK of several nucleoproteins, including the Nuclear thyroid hormone receptor β1. Because Estrogen can activate MAPK and cause MAPK-dependent serine phosphorylation of Nuclear Estrogen receptor (ER)α, we studied whether thyroid hormone also promoted MAPK-mediated ERα phosphorylation. Human breast cancer (MCF-7) cells were incubated with physiological concentrations of l-T4 or 17β-estradiol (E2) for 15 min to 24 h, and Nuclear ERα and serine-118-phosphorylated ERα were identified by Western blotting. Serine-118-phosphorylated ERα was recovered at 15 min in nuclei of MCF-7 cells exposed to either T4 or E2. The T4 effect was apparent at 15 min and peaked at 2 h, whereas the E2 effect was maximal at 4–6 h. T4-agarose was as effective as T4 in causing phosphorylation of ERα. T4 action on ERα was inhibited by PD 98059, an inhibitor of ERK1/2 phosphorylation, and by tetraiodothyroacetic acid, a T4 analog that bloc...
Hengyuan Tang - One of the best experts on this subject based on the ideXlab platform.
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thyroid hormone causes mitogen activated protein kinase dependent phosphorylation of the Nuclear Estrogen receptor
Endocrinology, 2004Co-Authors: Hengyuan Tang, Shenli Zhang, Faith B Davis, Hungyun Lin, Paul J DavisAbstract:Activated by thyroid hormone, the MAPK (ERK1/2) signaling pathway causes serine phosphorylation by MAPK of several nucleoproteins, including the Nuclear thyroid hormone receptor beta1. Because Estrogen can activate MAPK and cause MAPK-dependent serine phosphorylation of Nuclear Estrogen receptor (ER)alpha, we studied whether thyroid hormone also promoted MAPK-mediated ERalpha phosphorylation. Human breast cancer (MCF-7) cells were incubated with physiological concentrations of l-T(4) or 17beta-estradiol (E(2)) for 15 min to 24 h, and Nuclear ERalpha and serine-118-phosphorylated ERalpha were identified by Western blotting. Serine-118-phosphorylated ERalpha was recovered at 15 min in nuclei of MCF-7 cells exposed to either T(4) or E(2). The T(4) effect was apparent at 15 min and peaked at 2 h, whereas the E(2) effect was maximal at 4-6 h. T(4)-agarose was as effective as T(4) in causing phosphorylation of ERalpha. T(4) action on ERalpha was inhibited by PD 98059, an inhibitor of ERK1/2 phosphorylation, and by tetraiodothyroacetic acid, a T(4) analog that blocks cell surface-initiated actions of T(4) but is not itself an agonist. Electrophoretic mobility shift assay of Nuclear extracts from T(4)-treated and E(2)-treated cells showed similar specific protein-DNA-binding. Indexed by [(3)H]thymidine incorporation and Nuclear proliferating cell Nuclear antigen, MCF-7 cell proliferation was stimulated by T(4) and T(4)-agarose to an extent comparable with the effect of E(2). This T(4) effect was blocked by either PD 98059 or ICI 182,780, an ER antagonist. Thus, T(4), like E(2), causes phosphorylation by MAPK of Nuclear ERalpha at serine-118 in MCF-7 cells and promotes cell proliferation through the ER by a MAPK-dependent pathway.
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thyroid hormone causes mitogen activated protein kinase dependent phosphorylation of the Nuclear Estrogen receptor
Endocrinology, 2004Co-Authors: Hengyuan Tang, Shenli Zhang, Faith B Davis, Paul J DavisAbstract:Activated by thyroid hormone, the MAPK (ERK1/2) signaling pathway causes serine phosphorylation by MAPK of several nucleoproteins, including the Nuclear thyroid hormone receptor β1. Because Estrogen can activate MAPK and cause MAPK-dependent serine phosphorylation of Nuclear Estrogen receptor (ER)α, we studied whether thyroid hormone also promoted MAPK-mediated ERα phosphorylation. Human breast cancer (MCF-7) cells were incubated with physiological concentrations of l-T4 or 17β-estradiol (E2) for 15 min to 24 h, and Nuclear ERα and serine-118-phosphorylated ERα were identified by Western blotting. Serine-118-phosphorylated ERα was recovered at 15 min in nuclei of MCF-7 cells exposed to either T4 or E2. The T4 effect was apparent at 15 min and peaked at 2 h, whereas the E2 effect was maximal at 4–6 h. T4-agarose was as effective as T4 in causing phosphorylation of ERα. T4 action on ERα was inhibited by PD 98059, an inhibitor of ERK1/2 phosphorylation, and by tetraiodothyroacetic acid, a T4 analog that bloc...
Nancy A Muma - One of the best experts on this subject based on the ideXlab platform.
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extra Nuclear Estrogen receptor gpr30 regulates serotonin function in rat hypothalamus
Neuroscience, 2009Co-Authors: H Xu, Edward J Filardo, George Battaglia, Lydia L. Doncarlos, Gonzalo A. Carrasco, Eric R Prossnitz, Nancy A MumaAbstract:Abstract Selective serotonin reuptake inhibitors (SSRIs), such as Prozac®, are used to treat mood disorders. SSRIs attenuate (i.e. desensitize) serotonin 1A (5-HT1A) receptor signaling, as demonstrated in rats through decreased release of oxytocin and adrenocorticotropin hormone (ACTH) following 5-HT1A receptor stimulation. Maximal therapeutic effects of SSRIs for treatment of mood disorders, as well as effects on hypothalamic 5-HT1A receptor signaling in animals, take 1 to 2 weeks to develop. Estradiol also attenuates 5-HT1A receptor signaling, but, in rats, these effects occur within 2 days; thus, Estrogens or selective Estrogen receptor modulators may serve as useful short-term tools to accelerate desensitization of 5-HT1A receptors in response to SSRIs if candidate Estrogen receptor targets in the hypothalamus are identified. We found high levels of GPR30, which has been identified recently as a pertussis-toxin (PTX) sensitive G-protein-coupled Estrogen receptor, in the hypothalamic paraventricular nucleus (PVN) of rats. Double-label immunohistochemistry revealed that GPR30 co-localizes with 5-HT1A receptors, corticotrophin releasing factor (CRF) and oxytocin in neurons in the PVN. Pretreatment with PTX to the PVN before peripheral injections of 17-β-estradiol 3-benzoate completely prevented the reduction of the oxytocin response to the 5-HT1A receptor agonist, (+)-8-hydroxy-2-dipropylaminotetralin (DPAT). Treatment with the selective GRP30 agonist, G-1, attenuated 5-HT1A receptor signaling in the PVN as measured by an attenuated oxytocin (by 29%) and ACTH (by 31%) response to DPAT. This study indicates that a putative extra-Nuclear Estrogen receptor, GPR30, may play a role in estradiol-mediated attenuation of 5-HT1A receptor signaling, and potentially in accelerating the effects of SSRIs in treatment of mood disorders.
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extra Nuclear Estrogen receptor gpr30 regulates serotonin function in rat hypothalamus
Neuroscience, 2009Co-Authors: H Xu, Edward J Filardo, George Battaglia, Lydia L. Doncarlos, Gonzalo A. Carrasco, Eric R Prossnitz, Nancy A MumaAbstract:Abstract Selective serotonin reuptake inhibitors (SSRIs), such as Prozac®, are used to treat mood disorders. SSRIs attenuate (i.e. desensitize) serotonin 1A (5-HT1A) receptor signaling, as demonstrated in rats through decreased release of oxytocin and adrenocorticotropin hormone (ACTH) following 5-HT1A receptor stimulation. Maximal therapeutic effects of SSRIs for treatment of mood disorders, as well as effects on hypothalamic 5-HT1A receptor signaling in animals, take 1 to 2 weeks to develop. Estradiol also attenuates 5-HT1A receptor signaling, but, in rats, these effects occur within 2 days; thus, Estrogens or selective Estrogen receptor modulators may serve as useful short-term tools to accelerate desensitization of 5-HT1A receptors in response to SSRIs if candidate Estrogen receptor targets in the hypothalamus are identified. We found high levels of GPR30, which has been identified recently as a pertussis-toxin (PTX) sensitive G-protein-coupled Estrogen receptor, in the hypothalamic paraventricular nucleus (PVN) of rats. Double-label immunohistochemistry revealed that GPR30 co-localizes with 5-HT1A receptors, corticotrophin releasing factor (CRF) and oxytocin in neurons in the PVN. Pretreatment with PTX to the PVN before peripheral injections of 17-β-estradiol 3-benzoate completely prevented the reduction of the oxytocin response to the 5-HT1A receptor agonist, (+)-8-hydroxy-2-dipropylaminotetralin (DPAT). Treatment with the selective GRP30 agonist, G-1, attenuated 5-HT1A receptor signaling in the PVN as measured by an attenuated oxytocin (by 29%) and ACTH (by 31%) response to DPAT. This study indicates that a putative extra-Nuclear Estrogen receptor, GPR30, may play a role in estradiol-mediated attenuation of 5-HT1A receptor signaling, and potentially in accelerating the effects of SSRIs in treatment of mood disorders.
Lydia L. Doncarlos - One of the best experts on this subject based on the ideXlab platform.
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extra Nuclear Estrogen receptor gpr30 regulates serotonin function in rat hypothalamus
Neuroscience, 2009Co-Authors: H Xu, Edward J Filardo, George Battaglia, Lydia L. Doncarlos, Gonzalo A. Carrasco, Eric R Prossnitz, Nancy A MumaAbstract:Abstract Selective serotonin reuptake inhibitors (SSRIs), such as Prozac®, are used to treat mood disorders. SSRIs attenuate (i.e. desensitize) serotonin 1A (5-HT1A) receptor signaling, as demonstrated in rats through decreased release of oxytocin and adrenocorticotropin hormone (ACTH) following 5-HT1A receptor stimulation. Maximal therapeutic effects of SSRIs for treatment of mood disorders, as well as effects on hypothalamic 5-HT1A receptor signaling in animals, take 1 to 2 weeks to develop. Estradiol also attenuates 5-HT1A receptor signaling, but, in rats, these effects occur within 2 days; thus, Estrogens or selective Estrogen receptor modulators may serve as useful short-term tools to accelerate desensitization of 5-HT1A receptors in response to SSRIs if candidate Estrogen receptor targets in the hypothalamus are identified. We found high levels of GPR30, which has been identified recently as a pertussis-toxin (PTX) sensitive G-protein-coupled Estrogen receptor, in the hypothalamic paraventricular nucleus (PVN) of rats. Double-label immunohistochemistry revealed that GPR30 co-localizes with 5-HT1A receptors, corticotrophin releasing factor (CRF) and oxytocin in neurons in the PVN. Pretreatment with PTX to the PVN before peripheral injections of 17-β-estradiol 3-benzoate completely prevented the reduction of the oxytocin response to the 5-HT1A receptor agonist, (+)-8-hydroxy-2-dipropylaminotetralin (DPAT). Treatment with the selective GRP30 agonist, G-1, attenuated 5-HT1A receptor signaling in the PVN as measured by an attenuated oxytocin (by 29%) and ACTH (by 31%) response to DPAT. This study indicates that a putative extra-Nuclear Estrogen receptor, GPR30, may play a role in estradiol-mediated attenuation of 5-HT1A receptor signaling, and potentially in accelerating the effects of SSRIs in treatment of mood disorders.
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extra Nuclear Estrogen receptor gpr30 regulates serotonin function in rat hypothalamus
Neuroscience, 2009Co-Authors: H Xu, Edward J Filardo, George Battaglia, Lydia L. Doncarlos, Gonzalo A. Carrasco, Eric R Prossnitz, Nancy A MumaAbstract:Abstract Selective serotonin reuptake inhibitors (SSRIs), such as Prozac®, are used to treat mood disorders. SSRIs attenuate (i.e. desensitize) serotonin 1A (5-HT1A) receptor signaling, as demonstrated in rats through decreased release of oxytocin and adrenocorticotropin hormone (ACTH) following 5-HT1A receptor stimulation. Maximal therapeutic effects of SSRIs for treatment of mood disorders, as well as effects on hypothalamic 5-HT1A receptor signaling in animals, take 1 to 2 weeks to develop. Estradiol also attenuates 5-HT1A receptor signaling, but, in rats, these effects occur within 2 days; thus, Estrogens or selective Estrogen receptor modulators may serve as useful short-term tools to accelerate desensitization of 5-HT1A receptors in response to SSRIs if candidate Estrogen receptor targets in the hypothalamus are identified. We found high levels of GPR30, which has been identified recently as a pertussis-toxin (PTX) sensitive G-protein-coupled Estrogen receptor, in the hypothalamic paraventricular nucleus (PVN) of rats. Double-label immunohistochemistry revealed that GPR30 co-localizes with 5-HT1A receptors, corticotrophin releasing factor (CRF) and oxytocin in neurons in the PVN. Pretreatment with PTX to the PVN before peripheral injections of 17-β-estradiol 3-benzoate completely prevented the reduction of the oxytocin response to the 5-HT1A receptor agonist, (+)-8-hydroxy-2-dipropylaminotetralin (DPAT). Treatment with the selective GRP30 agonist, G-1, attenuated 5-HT1A receptor signaling in the PVN as measured by an attenuated oxytocin (by 29%) and ACTH (by 31%) response to DPAT. This study indicates that a putative extra-Nuclear Estrogen receptor, GPR30, may play a role in estradiol-mediated attenuation of 5-HT1A receptor signaling, and potentially in accelerating the effects of SSRIs in treatment of mood disorders.
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neuroprotection by estradiol
Progress in Neurobiology, 2001Co-Authors: Luis M Garciasegura, Inigo Azcoitia, Lydia L. DoncarlosAbstract:This review highlights recent evidence from clinical and basic science studies supporting a role for Estrogen in neuroprotection. Accumulated clinical evidence suggests that Estrogen exposure decreases the risk and delays the onset and progression of Alzheimer’s disease and schizophrenia, and may also enhance recovery from traumatic neurological injury such as stroke. Recent basic science studies show that not only does exogenous estradiol decrease the response to various forms of insult, but the brain itself upregulates both Estrogen synthesis and Estrogen receptor expression at sites of injury. Thus, our view of the role of Estrogen in neural function must be broadened to include not only its function in neuroendocrine regulation and reproductive behaviors, but also to include a direct protective role in response to degenerative disease or injury. Estrogen may play this protective role through several routes. Key among these are Estrogen dependent alterations in cell survival, axonal sprouting, regenerative responses, enhanced synaptic transmission and enhanced neurogenesis. Some of the mechanisms underlying these eAects are independent of the classically defined Nuclear Estrogen receptors and involve unidentified membrane receptors, direct modulation of neurotransmitter receptor function, or the known anti-oxidant activities of Estrogen. Other neuroprotective eAects of Estrogen do depend on the classical Nuclear Estrogen receptor, through which Estrogen alters expression of Estrogen responsive genes that play a role in apoptosis, axonal regeneration, or general trophic support. Yet another possibility is that Estrogen receptors in the membrane or cytoplasm alter phosphorylation cascades through direct interactions with protein kinases or that Estrogen receptor signaling may converge with signaling by other trophic molecules to confer resistance to injury. Although there is clear evidence that estradiol exposure can be deleterious to some neuronal populations, the potential clinical benefits of Estrogen treatment for enhancing cognitive function may outweigh the associated central and peripheral risks. Exciting and important avenues for future investigation into the protective eAects of Estrogen include the optimal ligand and doses that can be used clinically to confer benefit without undue risk, modulation of neurotrophin and neurotrophin receptor expression, interaction of Estrogen with regulated cofactors and coactivators that couple Estrogen receptors to basal transcriptional machinery, interactions of Estrogen with other survival and regeneration promoting factors, potential Estrogenic eAects on neuronal replenishment, and modulation of phenotypic choices by neural stem cells. 7 2000 Elsevier Science Ltd. All rights reserved.
