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      Effects of Estrogen in the Male Rat Medial Amygdala: Infusion of an Aromatase Inhibitor Lowers Mating and Bovine Serum Albumin-Conjugated Estradiol Implants Do Not Promote Mating

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          Abstract

          In male rats, copulatory behavior depends on estrogen-responsive neurons located in brain areas known to be crucial for mating. Blocking the aromatization of testosterone (T) to estradiol (E<sub>2</sub>) either throughout the brain or within the medial preoptic area (MPO) reduces mating, whereas E<sub>2</sub> treatment of either the MPO or the medial amygdala (MEA) maintains sexual behavior. The effects of T aromatization in the MEA have received less attention; therefore, 2 studies were done to further elucidate the effects of E<sub>2</sub> in the MEA. In experiment 1, gonadally intact male rats that showed robust mating behavior were administered chronic fadrozole, a nonsteroidal aromatase inhibitor, to the MEA to stop the conversion of T to E<sub>2</sub> and then paired with receptive females. Infusion of fadrozole to the MEA significantly lowered mating behavior in experimental males compared to vehicle-infused control males. To further investigate the mechanism by which E<sub>2</sub> acts in the MEA, in experiment 2, E<sub>2</sub> conjugated to bovine serum albumin (BSA-E<sub>2</sub>: a complex of E<sub>2 </sub>and a large protein that does not cross the plasma membrane, thereby restricting the action of E<sub>2</sub> to cell-surface signaling) was chronically administered bilaterally to the MEA of castrated, dihydrotestosterone-treated males. This treatment did not maintain mating behavior. These studies show that E<sub>2</sub> acts in the MEA to promote male sexual behavior and suggest an intercellular mechanism of E<sub>2</sub> action.

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          Cloning of a novel receptor expressed in rat prostate and ovary.

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            Mitochondrial localization of estrogen receptor beta.

            Estrogen receptors (ERs) are believed to be ligand-activated transcription factors belonging to the nuclear receptor superfamily, which on ligand binding translocate into the nucleus and activate gene transcription. To date, two ERs have been identified: ERalpha and ERbeta. ERalpha plays major role in the estrogen-mediated genomic actions in both reproductive and nonreproductive tissue, whereas the function of ERbeta is still unclear. In this study, we used immunocytochemistry, immunoblotting, and proteomics to demonstrate that ERbeta localizes to the mitochondria. In immunocytochemistry studies, ERbeta was detected with two ERbeta antibodies and found to colocalize almost exclusively with a mitochondrial marker in rat primary neuron, primary cardiomyocyte, and a murine hippocampal cell line. The colocalization of ERbeta and mitochondrial markers was identified by both fluorescence and confocal microscopy. No translocation of ERbeta into the nucleus on 17beta-estradiol treatment was seen by using immunocytochemistry. Immunoblotting of purified human heart mitochondria showed an intense signal of ERbeta, whereas no signals for nuclear and other organelle markers were found. Finally, purified human heart mitochondrial proteins were separated by SDS/PAGE. The 50,000-65,000 M(r) band was digested with trypsin and subjected to matrix-assisted laser desorption/ionization mass spectrometric analysis, which revealed seven tryptic fragments that matched with those of ERbeta. In summary, this study demonstrated that ERbeta is localized to mitochondria, suggesting a role for mitochondrial ERbeta in estrogen effects on this important organelle.
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              Specific binding sites for oestrogen at the outer surfaces of isolated endometrial cells.

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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                2006
                August 2006
                25 August 2006
                : 83
                : 2
                : 106-116
                Affiliations
                Department of Biology, Georgia State University, Atlanta, Ga., USA
                Article
                94400 Neuroendocrinology 2006;83:106–116
                10.1159/000094400
                16825796
                6b73ded0-dea6-4e2c-b403-ec13d9479403
                © 2006 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 23 December 2005
                : 01 June 2006
                Page count
                Figures: 4, Tables: 2, References: 69, Pages: 11
                Categories
                Original Paper

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Dihydrotestosterone,Sexual behavior,Fadrozole,Estrogen receptor

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