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      Estrogen Receptor-Beta Regulates Epithelial Cell Differentiation in the Mouse Ventral Prostate

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          Abstract

          The epithelium of the ventral prostate expresses high levels of ERβ (but no ERα). ERα is expressed in the stroma. Thus, in addition to the indirect effects of estrogen on the epithelium which are reported to be mediated by ERα, there is a direct estrogenic influence on prostatic epithelium mediated by ERβ. We have reported that loss of ERβ results in epithelial hypercellularity in the ventral prostate. In ERβ–/– mouse prostates, there is overexpression of the androgen receptor and of the antiapoptotic factor Bcl-2 in the prostate. Bcl-2 is an estrogen-regulated gene. It is normally expressed only in the basal cells in the prostate. This apparent expansion of the ‘stem cell-like population’ in the ERβ–/– mouse prostate has been further examined. We found a higher expression of cytokeratin 5 in ERβ–/– mouse prostates so that the ratio of cytokeratin 5 to that of 19 is much higher in ERβ–/– than in wild-type littermates. In addition, labeling of DNA with BrdU showed a 3.5-fold higher proliferation rate in ERβ–/– mouse prostate. Despite these clear differences, the piling up of epithelial cells never progressed to high-grade PIN-like lesions. Hyperplastic foci in ERβ–/– mice show accumulation of cells without signs of atypia, resembling low-grade PIN in humans. The reason for this appeared to be a high rate of cellular detachment and subsequent fall off into the lumen in ERβ–/– mice. The fall off phenomenon is possibly related to the finding that the expression of the cell adhesion molecule E-cadherin was very reduced. We conclude that in ERβ–/– mouse prostates, the epithelial cell population contains more epithelial cells in the intermediate stage of differentiation, possessing both the ability to proliferate as the basal cells and the ability to secrete as the highly differentiated luminal epithelium.

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          Author and article information

          Journal
          HRE
          Horm Res Paediatr
          10.1159/issn.1663-2818
          Hormone Research in Paediatrics
          S. Karger AG
          978-3-8055-7833-2
          978-3-318-01154-8
          1663-2818
          1663-2826
          2004
          October 2004
          17 November 2004
          : 62
          : Suppl 3
          : 115
          Affiliations
          Departments of Medical Nutrition and Bioscience, Karolinska Institute, Novum, Huddinge, Sweden
          Article
          80510 Horm Res 2004;62(suppl 3):115DOI: 10.1159/00008080510
          10.1159/000080510
          © 2004 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
          Pages: 1
          Categories
          Endocrinology of Ageing

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