17β-Estradiol Potentiates Kainate-Induced Currents via Activation of the cAMP Cascade

Gu, Qin; Moss, Robert L.

doi:10.1523/jneurosci.16-11-03620.1996

Cited by 328 publications

(216 citation statements)

References 58 publications

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“…Hence, effects of steroids with a latency of 10 minutes or less are often attributed to non-classical actions. For example, in dissociated hippocampal cells, E 2 increases kainate-induced currents in 3 minutes [23]. We have demonstrated that administration of E 2 improves affective processes within 10 minutes of administration when administered directly to the hippocampus [24], which supports the idea that some of E 2 's effects in the hippocampus for these processes are rapid.…”

Section: Rapid And/or Membrane Actions In the Hippocampus For E 2 'S supporting

confidence: 71%

Rapid and estrogen receptor beta mediated actions in the hippocampus mediate some functional effects of estrogen

Walf

Frye

2008

Steroids

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The steroid hormone, estradiol (E 2 ), has numerous targets in the central nervous system, including the hippocampus, which plays a key role in cognition and affective behavior. This review focuses on our evidence from studies in rodents that E 2 has diverse mechanisms in the hippocampus for its functional effects E 2 has rapid, membrane-mediated effects in the hippocampus to enhance cognitive performance. Administration of E 2 to the hippocampus of rats for 10 minutes following training enhances performance in a hippocampus-mediated task. Increased cell firing in the hippocampus occurs within this short time frame. Furthermore, administration of free E 2 or an E 2 conjugate, E 2 :bovine serum albumin (BSA), to the hippocampus produces similar performance-enhancing effects in this task, suggesting that E 2 has membrane actions in the hippocampus for these effects. Further evidence that E 2 has rapid, membrane-mediated effects is that co-administration of E 2 and inhibitors of mitogen activated protein kinase (MAPK), rather than intracellular E 2 receptors (ERs) or protein synthesis, attenuate the enhancing effects of E 2 in this task. Despite these data that demonstrate E 2 can have rapid and/or membrane-mediated effects in the hippocampus, there is clear evidence to suggest that intracellular ERs, particularly the β (rather than α) isoform of ERs, may be important targets for E 2 's functional effects for hippocampal processes. Administration of ligands that are specific for ERβ, but not ERα, have enhancing effects on hippocampal processes similar to that of E 2 (which has similar affinity for ERα and ERβ). These effects are attenuated when ERβ expression is knocked down in transgenic models or with central administration of antisense oligonucleotides. Thus, there may be a convergence of E 2 's actions through rapid, membranemediated effects and intracellular ERs and in the hippocampus for these functional effects.

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Section: Rapid And/or Membrane Actions In the Hippocampus For E 2 'S supporting

confidence: 71%

Rapid and estrogen receptor beta mediated actions in the hippocampus mediate some functional effects of estrogen

Walf

Frye

2008

Steroids

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“…However, we did not see any effects of 17α-estradiol on the GABA B response [17] or the μ-opioid response [21]. Similarly, Gu and Moss found that 17α-estradiol did not mimic the actions of E 2 in the hippocampus to potentiate the glutamate (kainate)-mediated currents in CA1 pyramidal neurons [35]. Likewise, Mermelstein et al found that 17α-estradiol was much less efficacious than E 2 in reducing L-type calcium currents in neostriatal neurons [36].…”

Section: Mer Is a Gpcr In Hypothalamic Pomc Neuronscontrasting

confidence: 46%

“…It was known previously that E 2 could rapidly modulate synaptic efficacy via activation of PKA [21,35,69,70]. Recently, we have delineated the upstream components of this signaling pathway that includes Gαq, phospholipase C, and PKCδ activation.…”

Section: Significancementioning

confidence: 99%

Modulation of hypothalamic neuronal activity through a novel G-protein-coupled estrogen membrane receptor

2008

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Estrogens are involved in the hypothalamic control of multiple homeostatic functions including reproduction, stress responses, energy metabolism, sleep cycles, temperature regulation, and motivated behaviors. The actions of 17β-estradiol (E 2 ) in the brain have been attributed to the activation of estrogen receptors α and β, as well as G-protein coupled or other membraneassociated estrogen receptors. Recently, we have identified a putative membrane-associated estrogen receptor that is coupled to desensitization of GABA B receptors in guinea pig and mouse hypothalamic neurons including proopiomelanocortin (POMC) neurons. We have synthesized a new nonsteroidal compound, STX, which selectively targets the Gαq-coupled phospholipase Cprotein kinase C-protein kinase A pathway, and have established that STX is more potent than E 2 in mediating this desensitization in an ICI 182, 780-sensitive manner in both guinea pig and mouse neurons. Both E 2 and STX are fully efficacious in estrogen receptor α, β knockout mice. Finally, we observed that the putative membrane-associated estrogen receptor is different from GPR30 in arcuate neurons using whole-cell patch recording in hypothalamic slices from GPR30 knockout mice. Collectively, these findings suggest that the mER is distinct from ERα, ERβ or GPR30.

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“…Also, E2 potentiates non-NMDA (kainate)-mediated excitation of hippocampal CA1 pyramidal neurons via activation of a cAMP/PKA pathway Moss, 1996, Gu andMoss, 1998). Based on the findings from the hippocampal slice, it was hypothesized that E2 activates a Gs-coupled receptor on the extracellular surface of hippocampal neurons, which operates in concert with an internal action of E2 on cAMP-dependent phosphorylation (Gu and Moss, 1998).…”

Section: Membrane-initiated Signaling Of E2mentioning

confidence: 99%

Membrane-initiated estrogen signaling in hypothalamic neurons

Kelly

Rønnekleiv

2008

Molecular and Cellular Endocrinology

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SummaryIt is well known that many of the actions of 17β-estradiol (E2) in the central nervous system are mediated via intracellular receptor/transcription factors that interact with steroid response elements on target genes. However, there is compelling evidence for membrane steroid receptors for estrogen in hypothalamic and other brain neurons. But it is not well understood how estrogen signals via membrane receptors, and how these signals impact not only membrane excitability but also gene transcription in neurons. Indeed, it has been known for sometime that E2 can rapidly alter neuronal activity within seconds, indicating that some cellular effects can occur via membrane delimited events. In addition, E2 can affect second messenger systems including calcium mobilization and a plethora of kinases to alter cell signaling. Therefore, this review will consider our current knowledge of rapid membrane-initiated and intracellular signaling by E2 in the hypothalamus, the nature of receptors involved and how they contribute to homeostatic functions. KeywordsERα; ERβ; GPCR (G protein-coupled receptor); mER (membrane estrogen receptor that is a GPCR) Electrophysiological studies in the 1960's and 1970's suggested that gonadal steroids could directly modulate the electrical activity of hypothalamic neurons

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17β-Estradiol Potentiates Kainate-Induced Currents via Activation of the cAMP Cascade

Cited by 328 publications

References 58 publications

Rapid and estrogen receptor beta mediated actions in the hippocampus mediate some functional effects of estrogen

Rapid and estrogen receptor beta mediated actions in the hippocampus mediate some functional effects of estrogen

Modulation of hypothalamic neuronal activity through a novel G-protein-coupled estrogen membrane receptor

Membrane-initiated estrogen signaling in hypothalamic neurons

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