Cited by 133Hypothalamic control of reproductive hormonesEstrogen and related hormone effectsNeuroscience and Neuropharmacology Research

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Differential Regulation of Gonadotropin-Releasing Hormone Neuron Activity and Membrane Properties by Acutely Applied Estradiol: Dependence on Dose and Estrogen Receptor Subtype

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Chu, Zhiguo, Andrade, Josefa, Shupnik, Margaret A., Moenter, Suzanne M.·2009·The Journal of Neuroscience

DOI 10.1523/jneurosci.0352-09.2009PMC PMC2744362

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Abstract

Gonadotropin-releasing hormone (GnRH) neurons are critical to controlling fertility.In vivo, estradiol can inhibit or stimulate GnRH release depending on concentration and physiological state. We examined rapid, nongenomic effects of estradiol. Whole-cell recordings were made of GnRH neurons in brain slices from ovariectomized mice with ionotropic GABA and glutamate receptors blocked. Estradiol was bath applied and measurements completed within 15 min. Estradiol from high physiological (preovulatory) concentrations (100 p m) to 100 n m enhanced action potential firing, reduced afterhyperpolarizing potential (AHP) and increased slow afterdepolarization amplitudes (ADP), and reduced IAHP and enhanced IADP. The reduction of IAHP was occluded by previous blockade of calcium-activated potassium channels. These effects were mimicked by an estrogen receptor (ER) β-specific agonist and were blocked by the classical receptor antagonist ICI182780. ERα or GPR30 agonists had no effect. The acute stimulatory effect of high physiological estradiol on firing rate was dependent on signaling via protein kinase A. In contrast, low physiological levels of estradiol (10 p m) did not affect intrinsic properties. Without blockade of ionotropic GABA and glutamate receptors, however, 10 p m estradiol reduced firing of GnRH neurons; this was mimicked by an ERα agonist. ERα agonists reduced the frequency of GABA transmission to GnRH neurons; GABA can excite to these cells. In contrast, ERβ agonists increased GABA transmission and postsynaptic response. These data suggest rapid intrinsic and network modulation of GnRH neurons by estradiol is dependent on both dose and receptor subtype. In cooperation with genomic actions, nongenomic effects may play a role in feedback regulation of GnRH secretion.

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See all 133

Authors: Chu, Z., Andrade, J., Shupnik, M. A., & Moenter, S. M.
Affiliations: University of Virginia (US)
ORCID: Moenter, Suzanne M.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2009-04-29
Volume: 29
Issue: 17
Pages: 5616-5627
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.0352-09.2009
PMC: PMC2744362
OpenAlex: W2009302214
Cited by: 133
References: 87
Citations by year: 2026: 1 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 7 · 2020: 6 · 2019: 4 · 2018: 11 · 2017: 6 · 2016: 10 · 2015: 11 · 2014: 9 · 2013: 11 · 2012: 12
FWCI: 18.84
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 183 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-34860, HD41469, R29HD034860, R01HD034860, R37HD034860, R01HD041469)
Topics: Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: GnRH neurons, estradiol, non-genomic estrogen signaling, estrogen receptor beta, estrogen receptor alpha, GPR30, action potential firing, afterhyperpolarization, calcium-activated potassium channels, protein kinase A, GABA transmission, glutamatergic neurotransmission, ovariectomized mice
MeSH terms: Animals, Dose-Response Relationship, Drug, Drug Administration Schedule, Estradiol, Female, Gonadotropin-Releasing Hormone, Membrane Potentials, Neurons, Receptors, Estrogen, Time Factors, Protein Subunits, Estrogen Receptor alpha, Estrogen Receptor beta, Mice

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Differential Regulation of Gonadotropin-Releasing Hormone Neuron Activity and Membrane Properties by Acutely Applied Estradiol: Dependence on Dose and Estrogen Receptor Subtype

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