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      Estrogens Act in Rat Hippocampus and Frontal Cortex to Produce Rapid, Receptor-Mediated Decreases in Serotonin 5-HT 1A Receptor Function

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          Abstract

          Previously our laboratory has shown that 17β-estradiol in vivo rapidly decreases R(+)-8-OH-DPAT-stimulated [<sup>35</sup>S]GTPγS binding (a measure of the initial biochemical event in the intracellular signaling pathway associated with 5-HT<sub>1A</sub> receptors) in the hippocampus, frontal cortex and amygdala. Studies were designed to determine if 17β-estradiol also acts in vitro on estrogen receptors in the hippocampus and frontal cortex to decrease 5-HT<sub>1A</sub> receptor function. Hippocampus and frontal cortex were dissected from ovariectomized rats and incubated for up to 3 h with various estrogens and antiestrogens; membrane homogenates were prepared for R(+)-8-OH-DPAT-stimulated [<sup>35</sup>S]GTPγS binding assays. 17β-Estradiol (10<sup>–6</sup>  M) decreased the maximal response in the R(+)-8-OH-DPAT-stimulated [<sup>35</sup>S]GTPγS binding assay in a time-dependent manner (observed at 30, 60 and 120 min) in both hippocampus and frontal cortex. The hormone, however, did not alter the EC<sub>50</sub> of R(+)-8-OH-DPAT. When hippocampus and frontal cortex were incubated in graded concentrations of 17β-estradiol for 1 h, the calculated EC<sub>50</sub> was approximately 2.5 × 10<sup>–8</sup>  M in both brain regions. The nonestradiol estrogen diethylstilbestrol also decreased 5-HT<sub>1A</sub> receptor function while the less potent estrogens 17α-estradiol and estriol were inactive at 5 × 10<sup>–8</sup>  M. The estrogen receptor antagonist ICI 182,780 potently and completely blocked the effects of 17β-estradiol on 5-HT<sub>1A</sub> receptor function with an apparent K<sub>B</sub> of approximately 10<sup>–9</sup>  M. These data demonstrate clearly that estrogens can act on estrogen receptors located in hippocampus and frontal cortex of ovariectomized rats to produce rapid heterologous decreases in 5-HT<sub>1A</sub> receptor function.

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          Comparative distribution of estrogen receptor-? and -? mRNA in the rat central nervous system

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            Cell Membrane and Nuclear Estrogen Receptors (ERs) Originate from a Single Transcript: Studies of ER  and ER  Expressed in Chinese Hamster Ovary Cells

            M Razandi (1999)
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              5-Hydroxytryptamine1A receptors are linked to a Gi-adenylate cyclase complex in rat hippocampus.

              The ability of 5-hydroxytryptamine (5-HT) and the 5-HT1A selective agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) to modulate adenylate cyclase activity was measured in rat hippocampus. In vitro ADP ribosylation of GTP-binding proteins by pertussis toxin in this tissue abolished both 5-HT- and 8-OH-DPAT-induced inhibition of forskolin-stimulated adenylate cyclase activity. These findings indicate that 5-HT1A receptors are linked a pertussis-sensitive Gi protein in rat hippocampus.
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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                2001
                March 2001
                02 April 2001
                : 73
                : 3
                : 166-174
                Affiliations
                Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas School of Medicine, Kansas City, Kans., USA
                Article
                54633 Neuroendocrinology 2001;73:166–174
                10.1159/000054633
                11307035
                6ea6dfe4-abd7-4da3-aa06-3a824ea59849
                © 2001 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
                Page count
                Figures: 4, Tables: 4, References: 29, Pages: 9
                Categories
                Gonadotropin Regulation: Central Correlates of Sex Steroids and Lactation

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Gonadal steroid receptors,Serotonin,Cortex,Guanine triphosphate,Hippocampus,Gonadal steroids,Serotonin receptors

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