Endocrine Abstracts (2006) 11 P669

Role of estrogen receptor α- or β-isoforms in sex-specific brain organization

F Goetz, AV Patchev & W Rohde

Institute of Experimental Endocrinology, Humboldt University Medical School (Charité - Universitätsmedizin Berlin), Berlin, Germany.

Male- or female-like neural control of gonadal function and reproductive behaviour is determined by sex-specific activation of estrogen receptors (ER) in the developing brain during a limited, critical period during ontogenesis. Exposure of the neonatal female brain to inappropriately high estrogen concentrations results in irreversible defeminization of neuroendocrine function which is manifested by disturbed cyclic ovarian activity and decreased female sexual receptivity in adulthood. Two major ER isoforms, alpha and beta, are present in neural circuits which govern ovarian cycle and sexual behavior. Using highly selective ERalpha or beta-agonists, this study provides evidence for distinct contribution of individual ER isoforms to the process of estrogen-dependent brain defeminization in the rat. Neonatal activation of the ERalpha results in impairment 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 ERbeta-selective agonist abolished cyclic gonadal function and had a strong defeminizing effect on the morphometry of the hypothalamic gonadotrophin ‘surge generator’ AVPV. However, neonatal ERbeta-activation failed to alter female sexual behaviour, responsiveness to estrogens and morphometric appearance of the behaviourally 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.

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