Neuroendocrinology
Hypothalamic Adrenal Axis
Lipocortin 1 Mediates an Early Inhibitory Action of Glucocorticoids on the Secretion of ACTH by the Rat Anterior Pituitary Gland in vitroTaylor A.D.a · Cowell A.-M.a · Flower J.b · Buckingham J.C.aaDepartment of Pharmacology, Charing Cross and Westminster Medical School, and bDepartment of Biochemical Pharmacology, William Harvey Research Institute, Medical College of St. Bartholomew’s Hospital, London, UK
|
|
Log in to MyKarger to check if you already have access to this content.
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.
Article / Publication Details
Received: March 24, 1993
Accepted: July 30, 1993
Published online: April 08, 2008
Issue release date: 1993
Number of Print Pages: 10
Number of Figures: 0
Number of Tables: 0
ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)
For additional information: https://www.karger.com/NEN
Abstract
Lipocortin 1 (LC1), a mediator of anti-inflammatory steroid action in some peripheral tissues, may contribute to the acute inhibitory effects of these steroids on hypothalamo-pituitary-adrenal (HPA) function. Accordingly, in the present study we have used an in vitro model to examine the potential role of this protein in the regulation of the release of corticotrophin (ACTH) from the anterior pituitary gland. Hypothalamic extracts (0.05-0.4 HE/ml), the 41 amino acid corticotrophin-releasing factor (CRF-41, 1-100 nM), the adenyl cyclase stimulator, forskolin (0.1 µM–10 mM), and the L-Ca2+ channel opener, BAY K8644 (0.01-10 mM), all caused concentration-dependent increases in the release in vitro of immunoreactive (ir)-ACTH from segments of rat anterior pituitary tissue. The secretory responses to submaximal concentrations of these secretagogues were overcome by preincubation of the tissue with dexamethasone (0.1 and 1 µM). LC1 was readily detectable by Western blotting in protein extracts of freshly excised pituitary tissue; a small proportion of the protein was found to be attached to the outer surface of the cell membranes where it was retained by a Ca2+-dependent mechanism. Exposure to dexamethasone (0.1 µM) in vitro did not affect the total LC1 content of the pituitary tissue but, over a 2-hour period, it caused a progressive two- to fivefold increase in the amount of LC1 attached to the outer surface of the cell; this response developed in parallel with the inhibitory effects of the steroid on ir-ACTH release. Both the dexamethasone-induced ‘externalization’ of LC1 by the pituitary tissue and the concomitant steroid-induced inhibition of peptide release were blocked by cycloheximide (1.0 µg/ml) but not by actinomycin D (0.5 µg/ml). A stable N-terminal lipocortin 1 fragment, LC11–188 (10 pg-10 ng/ml), attenuated (p < 0.01) the release of ir-ACTH evoked by HE (0.1 HE/ml), CRF-41 (1 nM), forskolin (1 mM) and BAY K8644 (1 nM). Conversely, inclusion of the anti-LC1 antibody in the medium substantially overcame the inhibitory effects of dexamethasone (0.1 µM) on the release of ir-ACTH evoked by the secretagogues whilst a control isotype matched antibody was without effect. The results suggest that LC1 plays a key role in effecting the acute inhibitory actions of glucocorticoids on the secretion of ir-ACTH by the rat anterior pituitary gland.
© 1993 S. Karger AG, Basel
Related Articles:
Article / Publication Details
Received: March 24, 1993
Accepted: July 30, 1993
Published online: April 08, 2008
Issue release date: 1993
Number of Print Pages: 10
Number of Figures: 0
Number of Tables: 0
ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)
For additional information: https://www.karger.com/NEN
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.
Get Permission
PubMed ID
