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      D 2 Dopamine-Receptor-Mediated Inhibition of Proliferation of Rat Lactotropes in Culture Is Accompanied by Changes in Cell Shape

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          Abstract

          Dopaminergic agonists are effective in vivo in inhibiting lactotrope proliferation and prolactin (PRL)-secreting pituitary tumors. The purpose of the present study was to demonstrate in vitro actions of dopaminergic agents on proliferation and cell shape of rat lactotropes. Anterior pituitary cells cultured with serum-free, chemically defined medium were treated with dopaminergic agents and were labeled with 5-bromo-2′-deoxyuridine (BrdU) for 3 h before the end of culture. BrdU-labeling indices indicative of the proliferation rate of lactotropes were determined by double immunofluorescence staining for BrdU and PRL. Treatment with dopamine for 21 h decreased BrdU-labeling indices of lactotropes in a dose-dependent manner with a nadir at 3 × 10<sup>–7</sup>  M. The inhibitory action of 10<sup>–5</sup>  M dopamine appeared 15 h after the initiation of treatment and became pronounced with time up to 33 h. The dopamine action was mimicked by treatment with the D<sub>2</sub> receptor agonist bromocriptine at concentrations over 10<sup>–9</sup>  M. Phase-contrast microscopy revealed that the flat polygonal cell shape of cultured lactotropes had changed to a round refractive cell shape after treatment with dopamine or bromocriptine, and that these changes in cell shape exactly paralleled those in the BrdU-labeling index. The changes in cell shape of lactotropes were accompanied by changes in subcellular distribution of actin filaments. Pretreatment with 10<sup>–7</sup>  M eticlopride, a D<sub>2</sub> receptor antagonist, blocked the dopamine- or bromocriptine-induced changes in both BrdU-labeling index and cell shape. These results suggest that (1) the in vitro experimental system established in the present study is a good model for studying the mechanism of the antiproliferative action of dopamine and (2) D<sub>2</sub>-receptor-mediated inhibition of proliferation of lactotropes in serum-free culture is closely related to changes in actin organization and cell shape.

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          Most cited references 2

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          Preserved Collisional Crustal Structure of the Southern Urals Revealed by Vibroseis Profiling

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            Bromocriptine inhibits incorporation of [3H]thymidine into rat pituitary tumor 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
              1998
              September 1998
              18 September 1998
              : 68
              : 3
              : 163-171
              Affiliations
              Departments of a Physiology and b Obstetrics and Gynecology, Yamanashi Medical University, Yamanashi, Japan
              Article
              54362 Neuroendocrinology 1998;68:163–171
              10.1159/000054362
              9734000
              © 1998 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: 6, References: 54, Pages: 9
              Categories
              Differentiation and Signaling in the Anterior Pituitary

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