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The Journal of Neuroscience, April 29, 2009, 29(17):5616-5627; doi:10.1523/JNEUROSCI.0352-09.2009

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

Zhiguo Chu,¹ Josefa Andrade,¹ Margaret A. Shupnik,^1,2 and Suzanne M. Moenter^1,3

Departments of ¹Medicine, ²Molecular Physiology and Biological Physics, and ³Cell Biology, University of Virginia, Charlottesville, Virginia 22908

Correspondence should be addressed to Suzanne M. Moenter, Departments of Medicine and Cell Biology, P.O. Box 800578, University of Virginia, Charlottesville, VA 22908. Email: Moenter{at}virginia.edu

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 pM) to 100 nM enhanced action potential firing, reduced afterhyperpolarizing potential (AHP) and increased slow afterdepolarization amplitudes (ADP), and reduced I_AHP and enhanced I_ADP. The reduction of I_AHP 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. ER 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 pM) did not affect intrinsic properties. Without blockade of ionotropic GABA and glutamate receptors, however, 10 pM estradiol reduced firing of GnRH neurons; this was mimicked by an ER agonist. ER 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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Received Jan. 22, 2009; revised March 16, 2009; accepted March 25, 2009.

Correspondence should be addressed to Suzanne M. Moenter, Departments of Medicine and Cell Biology, P.O. Box 800578, University of Virginia, Charlottesville, VA 22908. Email: Moenter{at}virginia.edu

This article has been cited by other articles:

				A. E. Herbison Rapid actions of oestrogen on gonadotropin-releasing hormone neurons; from fantasy to physiology? J. Physiol., November 1, 2009; 587(21): 5025 - 5030. [Abstract] [Full Text] [PDF]

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