Effect of the glucocorticoid receptor antagonist Org 34850 on fast and delayed feedback of corticosterone release

Spiga, F., Harrison, L. R., Wood, S. A., MacSweeney, C. P., Thomson, F. .J. , Craighead, M., Grassie, M. and Lightman, S. L. (2008) Effect of the glucocorticoid receptor antagonist Org 34850 on fast and delayed feedback of corticosterone release. Journal of Endocrinology, 196(2), pp. 323-330. (doi:10.1677/JOE-07-0503) (PMID:18252955)

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Abstract

We investigated the effect of the glucocorticoid receptor (GR) antagonist Org 34850 on fast and delayed inhibition of corticosterone secretion in response to the synthetic glucocorticoid methylprednisolone (MPL). Male rats were implanted with a catheter in the right jugular vein, for blood sampling and MPL administration, and with an s.c. cannula for Org 34850 administration. All experiments were conducted at the diurnal hormonal peak in the late afternoon. Rats were connected to an automated sampling system and blood samples were collected every 5 or 10 min. Org 34850 (10 mg/kg, s.c.) or vehicle (5% mulgofen in saline) was injected at 1630 h; 30 min later, rats received an injection of MPL (500 μg/rat, i.v.) or saline (0.1 ml/rat). We found that an acute administration of MPL rapidly decreased the basal corticosterone secretion and this effect was not prevented by acute pretreatment with Org 34850. However, blockade of GR with Org 34850 prevented delayed inhibition of MPL on corticosterone secretion measured between 4 and 12 h after MPL administration. Our data suggest an involvement of GR in modulating delayed, but not fast, inhibition induced by MPL on basal corticosterone secretion.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Thomson, Dr Fiona
Authors: Spiga, F., Harrison, L. R., Wood, S. A., MacSweeney, C. P., Thomson, F. .J., Craighead, M., Grassie, M., and Lightman, S. L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Journal of Endocrinology
Publisher:BioScientifica
ISSN:0022-0795
ISSN (Online):1479-6805
Copyright Holders:Copyright © 2008 Society for Endocrinology
First Published:First published in Journal of Endocrinology 196(2):323-330
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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