Log in to MyKarger to check if you already have access to this content.
Buy
FullText & PDF
Unlimited re-access via MyKarger
Unrestricted printing, no saving restrictions for personal use
read more
CHF 38.00 *
EUR 35.00 *
USD 39.00 *
Select
KAB
Buy a Karger Article Bundle (KAB) and profit from a discount!
If you would like to redeem your KAB credit, please log in.
Save over 20% compared to the individual article price.
Learn more
Rent via DeepDyve
Unlimited fulltext viewing of this article
Organize, annotate and mark up articles
Printing and downloading restrictions apply
Start free trial
Subscribe
Access to all articles of the subscribed year(s) guaranteed for 5 years
Unlimited re-access via Subscriber Login or MyKarger
Unrestricted printing, no saving restrictions for personal use
read more
Subcription rates
Select
* The final prices may differ from the prices shown due to specifics of VAT rules.
Article / Publication Details
Abstract
Introduction. The glucocorticoid receptor is pivotal to control corticotrophin (ACTH) secretion and its function is closely linked to the heat shock protein 90 (HSP90) chaperone complex. Impaired sensitivity to glucocorticoid feedback is a hallmark of human corticotroph adenomas, i.e., Cushing’s disease, a disorder with few medical treatment options. Silibinin, a HSP90 inhibitor, has been studied in tumoral corticotroph cells and its use proposed in Cushing’s disease. Aim of the present study was to further investigate the effect of silibinin on human corticotroph adenomas in vitro.
Methods. Seven human ACTH-secreting pituitary adenomas were established in culture and treated with 10 – 50 µM silibinin with/without dexamethasone for up to 72 hours. ACTH medium levels were measured and POMC and glucocorticoid receptor, i.e., NR3C1, gene expression assessed.
Results. Silibinin reduced spontaneous ACTH secretion and restored sensitivity to steroid negative feedback to a different extent in individual adenomas. POMC expression was decreased both in control and dexamethasone-treated wells in specimens sensitive to silibinin. Interestingly, silibinin reduced constitutive NR3C1 expression and reversed the dexamethasone-induced inhibition.
Conclusions. Our findings indicate that silibinin can inhibit ACTH synthesis and secretion in individual human corticotroph adenomas and directly affects NR3C1 gene expression. These results reveal promising effects of this HSP90 inhibitor on human corticotroph adenomas and support an innovative target treatment for patients with Cushing’s disease.
S. Karger AG, Basel
Article / Publication Details
Copyright / Drug Dosage / Disclaimer
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.
留言 (0)