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Definition of Estrogen Receptor Pathway Critical for Estrogen Positive Feedback to Gonadotropin-Releasing Hormone Neurons and Fertility

Open access
Wintermantel, Tim M., Campbell, Rebecca E., Porteous, Robert, Bock, Dagmar, Gröne, Hermann-Josef, Todman, Martin G., Korach, Kenneth S., Greiner, Erich, Pérez, Cristian A., Schütz, Günther, Herbison, Allan E.·2006·Neuron
DOI 10.1016/j.neuron.2006.07.023
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Abstract

Summary The mechanisms through which estrogen regulates gonadotropin-releasing hormone (GnRH) neurons to control mammalian ovulation are unknown. We found that estrogen positive feedback to generate the preovulatory gonadotropin surge was normal in estrogen receptor β knockout (ERβ) mutant mice but absent in ERα mutant mice. An ERα-selective compound was sufficient to generate positive feedback in wild-type mice. As GnRH neurons do not express ERα, estrogen positive feedback upon GnRH neurons must be indirect in nature. To establish the cell type responsible, we generated a neuron-specific ERα mutant mouse line. These mice failed to exhibit estrogen positive feedback demonstrating that neurons expressing ERα are critical. We then used GnRH neuron-specific Cre-dependent Pseudorabies virus tracing to show that the ERα-expressing neurons modulating GnRH neurons are located within rostral periventricular regions of the hypothalamus. These studies demonstrate ovulation is driven by estrogen actions upon ERα-expressing neuronal afferents to GnRH neurons.

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Authors
Wintermantel, T. M., Campbell, R. E., Porteous, R., Bock, D., Gröne, H.-J., Todman, M. G., Korach, K. S., Greiner, E., Pérez, C. A., Schütz, G., & Herbison, A. E.
Venue
Neuron
Publisher
Elsevier BV
Published
2006-10
Volume
52
Issue
2
Pages
271-280
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2006.07.023
OpenAlex
W2006727096
Cited by
598
References
0
FWCI
35.89
Type
journal article
Language
en
Open access
bronze

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