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      Ectopic ACTH Syndrome: Discrepancy between Somatostatin Receptor Status in vivo and ex vivo, and between Immunostaining and Gene Transcription for POMC and CRH

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          Abstract

          Objective: To characterize somatostatin receptor status in vivo and ex vivo and immunoreactivity and gene transcription for proopiomelanocortin (POMC) and corticotropin-releasing hormone (CRH) in a case of Cushing’s syndrome caused by a sporadic metastatic medullary thyroid carcinoma (MTC). Methods:<sup>111</sup>In octreoscan, analysis of tumorous mRNA transcripts for somatostatin receptor subtypes (SSTR) as well as for POMC and CRH. Results: The tissue was intensely positive by <sup>111</sup>In octreoscan but expressed only SSTR 1, 3 and 5. There was immunopositivity only for CRH, but gene transcription for both POMC and CRH was seen. Conclusions: (1) This first comparison between somatostatin receptor status in vivo and ex vivo in MTC shows a marked positive octreoscan despite absent SSTR 2 expression, and (2) this is the first report of a discrepancy between immunostaining and gene transcription for POMC and CRH.

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          The Diagnosis and Differential Diagnosis of Cushing's Syndrome and Pseudo-Cushing's States

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            Gene transcription of receptors for growth hormone-releasing peptide and somatostatin in human pituitary adenomas.

            Growth hormone (GH)-releasing peptides (GHRP) or secretagogs (GHS) constitute a family of synthetic compounds with potent and specific GH releasing activity. The receptor (GHS-R) has recently been cloned even though the endogenous ligand remains to be identified. GHRPs act both at the hypothalamic and the pituitary level through mechanisms involving amplification of GH-releasing hormone activity and functional somatostatin antagonism. In the present study we examined the co-expression of messenger RNA (mRNA) for GHS-R and all 5 somatostatin receptor subtypes (sstr 1-5) in 28 human pituitary tumors by RT-PCR. GHS-R transcription was detected in 11 out of 12 somatotroph adenomas and in 2 out of 2 prolactinomas, whereas GHS-R expression was detected in only 2 out of 14 clinically nonfunctioning adenomas (NFPA), and no expression was seen in the only ACTH secreting adenoma. Almost all tumors expressed sstr 2 mRNA (n = 24), whereas only 1 tumor expressed sstr 4 mRNA. The expression of sstr 3 mRNA was inversely associated with GHS-R expression (P < 0.001), which could be attributed to a high prevalence of sstr 3 expression in NFPA. This study suggests that GHS-R expression is predominantly observed in somatotroph adenomas and much less so in NFPA. Moreover, the presence of a distinct pattern of somatostatin receptor subtype co-expression is suggested, which may provide a molecular basis for the complex interaction between GHRPs and somatostatin.
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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
              1663-2818
              1663-2826
              2002
              2002
              30 May 2002
              : 57
              : 5-6
              : 200-204
              Affiliations
              aDepartment of Endocrinology and Metabolism, bLaboratory for Molecular Pathology, cDepartment of Nuclear Medicine, and dMedical Department M (Endocrinology and Diabetes), Aarhus University Hospital, Aarhus, Denmark; eDepartment of Pathology, University of Toronto, Ont., Canada
              Article
              58383 Horm Res 2002;57:200–204
              10.1159/000058383
              12053094
              7d71b029-d627-49a0-9911-fe4c18bd84a5
              © 2002 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.

              History
              Page count
              Figures: 3, Tables: 1, References: 11, Pages: 5
              Categories
              Case Report

              Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
              Corticotropin-releasing hormone,Cushing’s syndrome,Proopiomelanocortin,Medullary thyroid carcinoma

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