Journal ArticleDOI
Estrogen modulation of G-protein-coupled receptor activation of potassium channels in the central nervous system.
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TLDR
It is shown that E2 can modulate K+ channels in hypothalamic neurons that are involved in regulating numerous homeostatic functions through multiple intracellular signaling pathways and observed a direct, steroid‐induced hyperpolarization of GnRH neurons.Abstract:
Estrogen rapidly alters the excitability of hypothalamic neurons that are involved in regulating numerous homeostatic functions including reproduction, stress responses, feeding, and motivated behaviors. Neurosecretory neurons, such as gonadotropin-releasing hormone (GnRH) and dopamine neurons, and local circuitry neurons, such as pro-opiomelanocortin (POMC) and gamma-aminobutyric acid (GABA) neurons, are among those involved. We have identified membrane-initiated, rapid-signaling pathways through which 17beta-estradiol (E(2)) alters synaptic responses in these neurons using whole-cell patch recording in hypothalamic slices from ovariectomized female guinea pigs. E(2) rapidly uncouples micro -opioid and GABA(B) receptors from G-protein-gated inwardly rectifying K(+) (GIRK) channels in POMC and dopamine neurons as manifested by a reduction in the potency of micro -opioid and GABA(B) receptor agonists to activate these channels. These effects are mimicked by the selective E(2) receptor modulators raloxifene and 4OH-tamoxifen, the membrane impermeable E(2)-bovine serum albumin (BSA), but not by 17alpha-estradiol. Furthermore, the anti-estrogen ICI 182,780 antagonizes these rapid effects of E(2). Inhibitors of phospholipase C, protein kinase C, and protein kinase A block the actions of E(2), indicating that the E(2) receptor is G-protein-coupled to activation of this cascade. Conversely, estrogen enhances the efficacy of alpha1-adrenergic receptor agonists to inhibit apamin-sensitive small-conductance, Ca(2+)-activated K(+) (SK) currents in preoptic GABAergic neurons; it does so in both a rapid and sustained fashion. Finally, we observed a direct, steroid-induced hyperpolarization of GnRH neurons. These findings indicate that E(2) can modulate K(+) channels in hypothalamic (POMC, dopamine, GABA, GnRH) neurons that are involved in regulating numerous homeostatic functions through multiple intracellular signaling pathways.read more
Citations
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Anatomy and regulation of the central melanocortin system.
TL;DR: Given that the central melanocortin system is an active target for development of drugs for the treatment of obesity, diabetes and cachexia, it is important to understand the system in its full complexity, including the likelihood that the system also regulates the cardiovascular and reproductive systems.
Journal ArticleDOI
The neural basis of puberty and adolescence
Cheryl L. Sisk,Douglas L. Foster +1 more
TL;DR: The pubertal transition to adulthood involves both gonadal and behavioral maturation, and reproductive maturity is the product of developmentally timed, brain-driven and recurrent interactions between steroid hormones and the adolescent nervous system.
Journal ArticleDOI
Studying sex and gender differences in pain and analgesia: a consensus report
Joel D. Greenspan,Rebecca M. Craft,Linda LeResche,Lars Arendt-Nielsen,Karen J. Berkley,Roger B. Fillingim,Michael S. Gold,Anita Holdcroft,Stefan Lautenbacher,Emeran A. Mayer,Jeffrey S. Mogil,Anne Z. Murphy,Richard J. Traub +12 more
TL;DR: In this article, members of the Sex, Gender and Pain Special Interest Group of the International Association for the Study of Pain met to discuss the following: (1) what is known about sex and gender differences in pain and analgesia; (2) what are the "best practice" guidelines for pain research with respect to sex this article.
Consensus report Studying sex and gender differences in pain and analgesia: A consensus report
Joel D. Greenspan,Rebecca M. Craft,Linda LeResche,Lars Arendt-Nielsen,Karen J. Berkley,Roger B. Fillingim,Michael S. Gold,Anita Holdcroft,Stefan Lautenbacher,Emeran A. Mayer,Jeffrey S. Mogil,Anne Z. Murphy,Richard J. Traub +12 more
TL;DR: This document is intended to serve as a utilitarian and thought-provoking guide for future research on sex and gender differences in pain and analgesia, both for those currently working in this field as well as those still wondering, "Do I really need to study females?"
Journal ArticleDOI
Non-genomic actions of estrogens and their interaction with genomic actions in the brain.
TL;DR: There is evidence in this review, that membrane actions of estrogens, which activate these rapid signaling cascades, can also potentiate nuclear transcription in both the central nervous system and in non-neuronal cell lines.
References
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Journal ArticleDOI
Estradiol reduces calcium currents in rat neostriatal neurons via a membrane receptor.
TL;DR: Using whole-cell patch-clamp techniques, 17 beta-estradiol was found to reduce Ba2+ entry reversibly via Ca2+ channels in acutely dissociated and cultured neostriatal neurons, suggesting that at physiological concentrations, 17 alpha-Estradiol can have immediate actions on neostRIatal neurons via nongenomic signaling pathways.
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The mitogen-activated protein kinase pathway mediates estrogen neuroprotection after glutamate toxicity in primary cortical neurons.
TL;DR: A novel mechanism by which cytoplasmic actions of the estrogen receptor may activate the MAPK pathway is described, thus broadening the understanding of effects of estrogen in neurons, and providing evidence that activation of theMAPK pathway by estrogen participates in mediating neuroprotection via an estrogen receptor.
Journal ArticleDOI
ER-X: a novel, plasma membrane-associated, putative estrogen receptor that is regulated during development and after ischemic brain injury.
C. Dominique Toran-Allerand,Xiaoping Guan,Neil J. MacLusky,Tamas L. Horvath,Sabrina Diano,Meharvan Singh,E. Sander Connolly,Imam S. Nethrapalli,Alexander A. Tinnikov +8 more
TL;DR: It is proposed that the ER mediating activation of the MAPK cascade, a signaling pathway important for cell division, neuronal differentiation, and neuronal survival in the developing brain, is neither ER-α nor ER-β but a novel, plasma membrane-associated, putative ER with unique properties, which is designated “ER-X.”
Journal ArticleDOI
Rapid Membrane Effects of Steroids in Neuroblastoma Cells: Effects of Estrogen on Mitogen Activated Protein Kinase Signalling Cascade and c-fos Immediate Early Gene Transcription
TL;DR: It is shown that in the human neuroblastoma cell line SK-N-SH, the membrane impermeable conjugated 17beta-estradiol (E2BSA) activates mitogen activated protein kinase kinase (MAPKK or MEK) and induces the phosphorylation and activation of both ERK-1 and ERK
Journal ArticleDOI
17beta-estradiol enhances NMDA receptor-mediated EPSPs and long-term potentiation.
TL;DR: 17β-estradiol enhances NMDA receptor-mediated EPSPs and long-term potentiation and to test the hypothesis that gonadal steroid hormones influence CNS functioning through a variety of different mechanisms, this data indicates that the former improves CNS functioning and the latter enhances potentiation.