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      Effect of Androgens on Hypothalamic Pro-Opiomelanocortin

      Neuroendocrinology

      S. Karger AG

      β-Endorphin, Pro-opiomelanocortin, Androgens, Sex steroids, Hypothalamus

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          Abstract

          Testosterone and estradiol have been shown to affect the hypothalamic content of several pro-opiomelanocortin (POMC)-derived peptides in castrated male and female rats, respectively. It was unclear, however, whether the effects of testosterone on hypothalamic POMC were due to conversion by aromatization to estradiol or whether there were independent androgen actions on hypothalamic POMC. In order to answer this question, the effect of treatment with the nonaromitizable androgen 5-α-dihydrotestosterone (DHT) on the concentration of β-endorphin (β-EP) in the medial basal hypothalamus (MBH) was studied in castrated male rats and compared to the effect of treatment with testosterone or estradiol. The concentrations of two other POMC-derived peptides, corticotropin-like intermediate lobe peptide (CLIP) and α-MSH were measured as well. Adult male rats were castrated and received either no treatment or treatment with subcutaneously implanted silastic capsules, containing either DHT, testosterone or estradiol, designed to produce steroid levels in a physiological range. After 4 weeks the mean concentration of β-EP in the MBH of the untreated castrated rats was 1,640 ± 56 fmol/mg protein. This was reduced significantly to 1,184 + 74 fmol/mg protein after DHT treatment (p < 0.001). Similar reductions to 1,340 + 95 and 1,130 ± 85 fmol/mg protein were noted after testosterone and estradiol treatment, respectively. The mean CLIP concentration of 1,870 ± 73 fmol/mg protein in the untreated animals fell to 1,390 ± 95 after DHT (p < 0.001) compared to 1,520 ± 105 and 1,260 ± 101 after testosterone and estradiol treatment, respectively. α-MSH was similarly reduced from 911 ± 42 fmol/mg protein to 723 ± 54 after DHT (p < 0.02) as compared to 726 ± 39 and 627 ± 31 after testosterone and estradiol treatment. Reverse-phase high-performance liquid chromatography was performed on extracts of the MBH from individual castrated rats with and without DHT treatment in order to characterize the β-EP immunoactivity. The elution profile of the β-EP immunoactivity was very similar in both cases. Thus although DHT treatment is associated with a fall in the concentration of β-EP in the MBH, there does not appear to be a change in the processing of β-EP in the MBH. These results indicate that treatment with either testosterone or estradiol produces significant reductions in the hypothalamic concentrations of β-EP, CLIP, and α-MSH. The effectiveness of DHT in this respect demonstrates that there are independent androgen actions on hypothalamic POMC.

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          Author and article information

          Journal
          NEN
          Neuroendocrinology
          10.1159/issn.0028-3835
          Neuroendocrinology
          S. Karger AG
          0028-3835
          1423-0194
          1988
          1988
          02 April 2008
          : 47
          : 2
          : 164-168
          Affiliations
          Department of Medicine, Columbia University College of Physicians & Surgeons, New York, N.Y., USA
          Article
          124908 Neuroendocrinology 1988;47:164–168
          10.1159/000124908
          2830552
          © 1988 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: 5
          Categories
          Original Paper

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