Neuron
Volume 52, Issue 2, 19 October 2006, Pages 271-280
Journal home page for Neuron

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

https://doi.org/10.1016/j.neuron.2006.07.023Get rights and content
Under an Elsevier user license
open archive

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 a GnRH neuron-specific Pseudorabies virus (PRV) tracing approach to show that the ERα-expressing neurons innervating GnRH neurons are located within rostral periventricular regions of the hypothalamus. These studies demonstrate that ovulation is driven by estrogen actions upon ERα-expressing neuronal afferents to GnRH neurons.

MOLNEURO
SIGNALING

Cited by (0)

5

These authors contributed equally to this work.

6

Present address: Schering AG, Muellerstrasse 178, D-13342 Berlin, Germany.

7

Present address: Evotec AG, Schnackenburgalle 114, D-22525 Hamburg, Germany.