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Differential role of estrogen receptor isoforms in sex‐specific brain organization
Author(s) -
Patchev Alexandre V.,
Götz Franziska,
Rohde Wolfgang
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-1959fje
Subject(s) - endocrinology , medicine , estrogen , preoptic area , estrogen receptor alpha , estrogen receptor , biology , estrous cycle , gene isoform , hypothalamus , neuroscience , biochemistry , cancer , breast cancer , gene
Transient activation of estrogen receptors (ER) in the developing brain during a limited perinatal “window of time” is recognized as a key mechanism of defeminization of neural control of reproductive function and sexual behavior. Two major ER isoforms, α and β, are present in neural circuits that govern ovarian cycle and sexual behavior. Using highly selective ER agonists, this study provides the first evidence for distinct contribution of individual ER isoforms to the process of estrogen dependent defeminization. Neonatal activation of the ERα in female rats resulted in abrogation of cyclic ovarian activity and female sexual behavior in adulthood. These effects are associated with male‐like alterations in the morphology of the anteroventral periventricular (AVPV) and sexually dimorphic nucleus of the preoptic area (SDN‐POA), as well as refractoriness to estrogen‐mediated induction of sexual receptivity. Exposure to an ERβ‐selective agonist induced persistent estrus and had a strong defeminizing effect on the hypothalamic gonadotropin “surge generator” AVPV. However, neonatal ERβ activation failed to alter female sexual behavior, responsiveness to estrogens and morphometric features of the behaviorally relevant SDN‐POA. Thus, although co‐present in several brain regions involved in the control of female reproductive function, ER isoforms convey different, and probably not synergistic, chemical signals in the course of neonatal sex‐specific brain organization.