Mechanism of the Rapid Effect of 17β-Estradiol on Medial Amygdala Neurons

Nabekura, Junichi; Osuga, Yutaka; Minami, Taketsugu; Mizuno, Yuji; Fukuda, Atsuo

doi:10.1126/science.3726531

Cited by 262 publications

(122 citation statements)

References 24 publications

Supporting

Mentioning

116

Contrasting

Unclassified

Order By: Relevance

“…The ovary in several species releases Ca2+ from intracellular stores within seconds of E, exposure, perhaps via a "nonclassical" receptor (Morley et al, 1992). In another population of guinea pig hypothalamic neurons, E, directly modulates a potassium conductance, possibly via modulation of intracellular nucleotides (Kelly et al, 1984;Nabekura et al, 1986;Minami et al, 1990). A similar effect was seen in some neurons in the present study, but there was no decrease in DAMGO potency in any of these neurons following E, application (n = 8).…”

Section: Potential Mechanisms Of E Actionsupporting

confidence: 58%

The potency of mu-opioid hyperpolarization of hypothalamic arcuate neurons is rapidly attenuated by 17 beta-estradiol

1994

View full text Add to dashboard Cite

The mu-opioid agonist DAMGO (Tyr-D-Ala-Gly-MePhe-Gly-ol) hyperpolarizes the majority of arcuate hypothalamic (ARC) neurons by opening an inwardly rectifying potassium conductance. The EC50 for the DAMGO- induced hyperpolarization was 60 +/- 3 nM in ARC neurons from ovariectomized guinea pigs. Superfusion of 17 beta-estradiol (E2; 100 nM) for 20 min in vitro resulted in a significant decrease in DAMGO potency (EC50 = 212 +/- 16 nM) in 40% of the neurons that were tested. This rapid effect of E2 on the mu-opioid response was not mimicked by the biologically inactive isomer 17 alpha-estradiol. Multiple concentrations of E2 were used to generate an E2 concentration-response curve, with an EC50 of 9 nM and a maximal increase in the DAMGO EX50 of 411% of controls. The membrane properties and firing rate of E2- sensitive and E2-insensitive neurons were not different. Streptavidin- FITC labeling did not reveal any significant morphological differences between the groups, but a higher number of E2-sensitive cells was found in the lateral ARC and cell-poor zone. Moreover, immunocytochemical staining of the recorded cells revealed that beta-endorphin neurons were among those sensitive to E2. Therefore, E2 could increase beta- endorphin release by decreasing the potency of beta-endorphinergic autoinhibition, thus increasing the tonic opioid inhibition of E2- insensitive cells. Furthermore, the diffuse projections of hypothalamic beta-endorphin neurons would allow E2 to alter processes throughout the brain, as well as having local effects in the hypothalamus.

show abstract

Section: Potential Mechanisms Of E Actionsupporting

confidence: 58%

The potency of mu-opioid hyperpolarization of hypothalamic arcuate neurons is rapidly attenuated by 17 beta-estradiol

1994

View full text Add to dashboard Cite

show abstract

“…Using intracellular recording techniques, it was found that fast perfusion of estrogen (100 pM) hyperpolarized arcuate neurons within seconds in a hypothalamic slice preparation and that this effect was reversed within minutes of washing out estrogen (Kelly et al, 1980). Similar actions of E2 were also demonstrated in hypothalamic ventromedial nucleus (VMH) and amygdala neurons, even in the presence of protein synthesis inhibitors (Nabekura et al, 1986, Minami et al, 1990. Later, it was found that GnRH neurons, identified post hoc using a combination of intracellular dye labeling and immunocytochemical staining, were a target of estrogen actions (Kelly et al, 1984).…”

mentioning

confidence: 86%

Membrane-initiated estrogen signaling in hypothalamic neurons

Kelly

Rønnekleiv

2008

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

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

show abstract

“…In contrast, estrogen has also been found to produce short-term actions on the electrical properties of neurons and transmitter release. The rapid onset and time course of these effects suggest that they are distinct from the genomic mechanism of action and indicate that estrogen may act on membrane recep-tors or other cellular components to alter neuronal events (Nabekura et al, 1986;Smith et al, 1987Smith et al, , 1989Minami et al, 1990;Kelly et al, 1992;Majewska, 1992;Paul and Purdy, 1992). However, the mechanisms to account for the rapid actions of estrogen have remained elusive.…”

mentioning

confidence: 97%

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

1996

View full text Add to dashboard Cite

Evidence for nongenomic actions of steroids is now coming from a variety of fields of steroid research. Mechanisms of steroid action are being studied with regard to the membrane receptors and the activation of second messengers. The present study investigated the mechanism for the rapid effect of estrogen on acutely dissociated hippocampal CA1 neurons by using the whole-cell, voltage-clamp recording. Under the perforated patch configuration, 17P-estradiol potentiated kainateinduced currents in 38% of tested neurons. The potentiation was stereospecific, rapid in onset, and reversible after the removal of the steroid. Dose-response curves show that the potentiation by l-/P-estradiol was evident at a concentration as low as 10 nM and saturated at IO PM. 17/3-Estradiol did not affect the kinetics (i.e., affinity and cooperativity) and reversal potential of kainate-induced currents. This suggests that the potentiation did not result from direct interaction with kainate receptors nor the activation of ion channels other than kainate receptor-channels.The potentiation by 17/3-estradiol was similar to the enhancement of kainate-induced currents evoked by 8-bromo-CAMP, and was modulated by an inhibitor of phosphodiesterase (IBMX). The estrogen potentiation was blocked by a specific blocker of PKA (&I-CAMPS). Under standard recording configuration, the effect was significantly affected by intracellular perfusing with GDP-p-S or GTP-y-S. The data suggest that the potentiation of kainate-induced currents by 17P-estradiol was likely a G-protein(s) coupled, CAMPdependent phosphorylation event. By involvement of this nongenomic mechanism, estrogen may play a role in the modulation of excitatory synaptic transmission in the hippocampus.

show abstract

Mechanism of the Rapid Effect of 17β-Estradiol on Medial Amygdala Neurons

Cited by 262 publications

References 24 publications

The potency of mu-opioid hyperpolarization of hypothalamic arcuate neurons is rapidly attenuated by 17 beta-estradiol

The potency of mu-opioid hyperpolarization of hypothalamic arcuate neurons is rapidly attenuated by 17 beta-estradiol

Membrane-initiated estrogen signaling in hypothalamic neurons

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

Contact Info

Product

Resources

About