Gender differences exist in the development of the nigrostriatal dopamine system, and in the incidence and course of pediatric and adult neuropsychiatric diseases in which this system is implicated. The medium size spiny neuron (MSN) is the major output neuron of the caudate nucleus. It receives a large dopaminergic input from the substantia nigra, and 96% of the MSNs express DARPP-32, a dopamine and cyclic AMP-regulated phosphoprotein and key mediator of dopamine function. There are few examples, however, of direct effects of sex hormones, including 17β-estradiol (E2), on the MSN. We report that in vitro, E2 (10–50 nM) promotes MSN phenotypic maturation, as determined by increased soma size, neurite length, and DARPP-32 protein levels. Treatment with the ‘anti-estrogen’ ICI 182,780 or the partial-agonist tamoxifen also increases DARPP-32 levels, but when added to E2, ICI 182,780 only prevents the increase in DARPP-32 levels and increase in soma size and neurite length. Surprisingly, maturation effects are more robust in cells derived exclusively from female embryos. Western blot analysis of protein lysates and immunocytochemistry of cultured MSNs reveals the presence of the estrogen receptor β (ERβ). These data suggest that ERβ may mediate the differentiating effect of E2 on embryonic MSNs, and provide new avenues of investigation for the role of sex hormones in the development of the striatum and in diseases affecting the basal ganglia.
© 2004 S. Karger AG, Basel
Article / Publication Details
Published online: 7/28/2004
Issue release date: 2004
Number of Print Pages: 9
Number of Figures: 4
Number of Tables: 1
ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)
For additional information: http://www.karger.com/NEN
Copyright / Drug Dosage / Disclaimer
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 or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
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.