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      17β-Estradiol Modulates hMT 1 Melatonin Receptor Function

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          Abstract

          Estrogen modulates expression and function of G-protein-coupled receptors. The goal of this study was to assess the effect of 17β-estradiol (10 n M) exposure for 1 (E1) or 6 (E6) days on density and function of hMT<sub>1</sub> and hMT<sub>2</sub> melatonin receptors expressed in Chinese hamster ovary (CHO) cells (CHO-MT<sub>1</sub>/CHO-MT<sub>2</sub> cells). This strain of CHO cells expressed both estrogen receptor alpha and beta mRNAs, as determined by RT-PCR amplification. 17β-Estradiol treatment did not modify the affinity of either receptor; however, it significantly increased the density of 2-[<sup>125</sup>I]iodomelatonin-binding sites in CHO-MT<sub>2</sub> cells. 17β-Estradiol treatment (1–6 days) did not affect the potency of melatonin to inhibit forskolin stimulation of cAMP formation through activation of either MT<sub>1</sub> or MT<sub>2</sub> receptors; however, it significantly attenuated the maximal inhibition of forskolin-stimulated cAMP formation induced by melatonin (0.01–1 µ M) in CHO-MT<sub>1</sub> cells. Melatonin stimulation of [<sup>35</sup>S]GTPγS binding to CHO-MT<sub>1</sub> cell membranes was also attenuated following estradiol treatment. The inverse agonist luzindole reduced basal [<sup>35</sup>S]GTPγS binding in estradiol-treated cells but not in control CHO-MT<sub>1</sub> cells, suggesting that estradiol promotes constitutive activity of MT<sub>1</sub> melatonin receptors. We suggest that 17β-estradiol differentially affects MT<sub>1</sub> and MT<sub>2</sub> melatonin receptor functions, attenuates melatonin responses through activation of MT<sub>1</sub> receptors, and increases the MT<sub>2</sub> receptors density.

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          Most cited references 29

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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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              Oestrogen and attacks of migraine with and without aura.

              During women's reproductive years, migraine is three times more common than in men of a similar age. Although this female preponderance is commonly assumed to be associated with the additional trigger of fluctuating sex hormones of the menstrual cycle, few studies have been done to confirm or refute this. This review is confined to the relation between oestrogen and attacks of migraine. The evidence for an association between oestrogen "withdrawal" and attacks of migraine without aura is presented, as well as evidence for an association between high oestrogen states and attacks of migraine with aura. Only clinical data are presented here.
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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                2005
                July 2005
                06 July 2005
                : 81
                : 2
                : 87-95
                Affiliations
                Departments of aMolecular Pharmacology and Biological Chemistry and bPsychiatry and Behavioral Science, Northwestern University Feinberg School of Medicine, and cNorthwestern Drug Discovery Program, Northwestern University, Chicago, Ill., USA
                Article
                84897 Neuroendocrinology 2005;81:87–95
                10.1159/000084897
                15809517
                © 2005 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.

                Page count
                Figures: 5, Tables: 1, References: 40, Pages: 9
                Categories
                Original Paper

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