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The Journal of Neuroscience, August 29, 2007, 27(35):9294-9300; doi:10.1523/JNEUROSCI.0592-07.2007

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Behavioral/Systems/Cognitive
Membrane Estrogen Receptor- Interactions with Metabotropic Glutamate Receptor 1a Modulate Female Sexual Receptivity in Rats

Phoebe Dewing,¹ Marissa I. Boulware,² Kevin Sinchak,¹ Amy Christensen,¹ Paul G. Mermelstein,² and Paul Micevych¹

¹Department of Neurobiology and Laboratory of Neuroendocrinology of the Brain Research Institute, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California 90095, and ²Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455

Correspondence should be addressed to Dr. Paul Micevych, 73-078 CHS, Department of Neurobiology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095-1763. Email: pmicevych{at}mednet.ucla.edu

In rats, female sexual behavior is regulated by a well defined limbic–hypothalamic circuit that integrates sensory and hormonal information. Estradiol activation of this circuit results in µ-opioid receptor (MOR) internalization in the medial preoptic nucleus, an important step for full expression of sexual receptivity. Estradiol acts through both membrane and intracellular receptors to influence neuronal activity and behavior, yet the mechanism(s) and physiological significance of estradiol-mediated membrane responses in vivo have remained elusive. Recent in vitro evidence found that stimulation of membrane-associated estrogen receptor- (ER) led to activation of metabotropic glutamate receptor 1a (mGluR1a). Furthermore, mGluR1a signaling was responsible for the observed downstream effects of estradiol. Here we present data that show that ER and mGluR1a directly interact to mediate a rapid estradiol-induced activation of MOR in the medial preoptic nucleus, leading to female sexual receptivity. In addition, blockade of mGluR1a in the arcuate nucleus of the hypothalamus resulted in a significant attenuation of estradiol-induced MOR internalization, leading to diminished female sexual behavior. These results link membrane-initiated estradiol actions to neural events modulating behavior, demonstrating the physiological importance of ER-to-mGluR1a signaling.

Key words: mGluR1a; estradiol; arcuate nucleus; lordosis; µ-opioid receptor internalization; coimmunoprecipitation

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Received Feb. 10, 2007; revised June 8, 2007; accepted July 5, 2007.

Correspondence should be addressed to Dr. Paul Micevych, 73-078 CHS, Department of Neurobiology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095-1763. Email: pmicevych{at}mednet.ucla.edu

This article has been cited by other articles:

				P. Micevych and K. Sinchak Synthesis and Function of Hypothalamic Neuroprogesterone in Reproduction Endocrinology, June 1, 2008; 149(6): 2739 - 2742. [Abstract] [Full Text] [PDF]

				M. I. Boulware, H. Kordasiewicz, and P. G. Mermelstein Caveolin Proteins Are Essential for Distinct Effects of Membrane Estrogen Receptors in Neurons J. Neurosci., September 12, 2007; 27(37): 9941 - 9950. [Abstract] [Full Text] [PDF]

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