Definition of estrogen receptor pathway critical for estrogen positive feedback to gonadotropin-releasing hormone neurons and fertility.

Abstract:

: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 beta knockout (ERbeta) mutant mice, but absent in ERalpha mutant mice. An ERalpha-selective compound was sufficient to generate positive feedback in wild-type mice. As GnRH neurons do not express ERalpha, estrogen positive feedback upon GnRH neurons must be indirect in nature. To establish the cell type responsible, we generated a neuron-specific ERalpha mutant mouse line. These mice failed to exhibit estrogen positive feedback, demonstrating that neurons expressing ERalpha are critical. We then used a GnRH neuron-specific Pseudorabies virus (PRV) tracing approach to show that the ERalpha-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 ERalpha-expressing neuronal afferents to GnRH neurons.

journal_name

Neuron

journal_title

Neuron

authors

Wintermantel TM,Campbell RE,Porteous R,Bock D,Gröne HJ,Todman MG,Korach KS,Greiner E,Pérez CA,Schütz G,Herbison AE

doi

10.1016/j.neuron.2006.07.023

subject

Has Abstract

pub_date

2006-10-19 00:00:00

pages

271-80

issue

2

eissn

0896-6273

issn

1097-4199

pii

S0896-6273(06)00588-5

journal_volume

52

pub_type

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