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      Hormonal Regulation of Prolactin Release by Human Prolactinoma Cells Cultured in Serum-Free Conditions

      a , a , b

      Hormone Research in Paediatrics

      S. Karger AG

      PRL, Prolactinoma cells, Culture, Dopamine-TRH interactions, T3, E2

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          Abstract

          Thyrotropin-releasing hormone (TRH) stimulates the prolactin (PRL) release from normal lactotrophs or tumoral cell line GH3. This effect is not observed in many patients with PRL-secreting tumors. We examined in vitro the PRL response to TRH on cultured human PRL-secreting tumor cells (n = 10) maintained on an extracellular matrix in a minimum medium (DME + insulin, transferrin, selenium). Addition of 10<sup>-8</sup> M TRH to 4 × 10<sup>4</sup> cells produced either no stimulation of PRL release (n = 6) or a mild PRL rise of 32 ± (SE) 11 % (n = 4) when measured 1 2 and 24 h after TRH addition. When tumor cells were preincubated for 24 h with 5 × 10<sup>-11</sup> M bromocriptine, a 47 ± 4% inhibition of PRL release was obtained. When TRH (10<sup>-8</sup> M) was added, 24 h after bromocriptine, it produced a 85 ± 25% increase of PRL release (n = 8). This stimulation of PRL release was evident when measured 1 h after TRH addition and persisted for 48 h. The half maximal stimulatory effect of TRH was 2 × 10<sup>-10</sup> M and the maximal effect was achieved at 10<sup>-9</sup> M TRH. When tumor cells were pretreated with various concentrations of triiodothyronine (T3), the PRL release was inhibited by 50% with 5 × 10<sup>-11</sup> M T3 and by 80% with 10<sup>-9</sup> MT3. Successive addition of TRH (10<sup>-8</sup> M) was unable to stimulate PRL release at any concentration of T3. The addition of 10<sup>-8</sup> M estradiol for up to 16 days either stimulated or had no effect upon the PRL basal release according to the cases. In all cases tested (n = 4), preincubation of the tumor cells with estradiol (10<sup>-8</sup> M) modified the inhibition of PRL release induced by bromocriptine with a half-inhibitory concentration displaced from 3 × 10<sup>-11</sup> M (control) to 3 × 10<sup>-10</sup> M (estradiol). These data demonstrate that the absence of TRH effect observed in some human prolactinomas is not linked to the absence of TRH receptor in such tumor cells. TRH responsiveness is always restored in the presence of dopamine (DA) at appropriate concentration. This TRH/DA interaction seems specific while not observed under T3 inhibition of PRL. Furthermore, estrogens, while presenting a variable stimulatory effect upon basal PRL, antagonize the dopaminergic inhibition of PRL release.

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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
          978-3-8055-4237-1
          978-3-318-01981-0
          1663-2818
          1663-2826
          1985
          1985
          28 November 2008
          : 22
          : 3
          : 153-163
          Affiliations
          aLaboratoire de Neuroendocrinologie Expérimentale, et bDépartement de Neurochirurgie, Centre Hospitalo Universitaire de Marseille, France
          Article
          180089 Horm Res 1985;22:153–163
          10.1159/000180089
          3932176
          © 1985 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: 11
          Categories
          Prolactin

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