On the Role of Brain Mineralocorticoid (Type I) and Glucocorticoid (Type II) Receptors in Neuroendocrine Regulation (original) (raw)
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Research Articles| April 02 2008
Rudolf Magnus Institute for Pharmacology, Medical Faculty, University of Utrecht, The Netherlands
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Rudolf Magnus Institute for Pharmacology, Medical Faculty, University of Utrecht, The Netherlands
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Rudolf Magnus Institute for Pharmacology, Medical Faculty, University of Utrecht, The Netherlands
Search for other works by this author on:
Rudolf Magnus Institute for Pharmacology, Medical Faculty, University of Utrecht, The Netherlands
Search for other works by this author on:
Neuroendocrinology (1989) 50 (2): 117–123.
Abstract
Administrations of the glucocorticoid receptor antagonist (anti-glucocorticoid, RU38486) and the mineralocorticoid antagonist (anti-mineralocorticoid, RU28318) followed by frequent, sequential blood sampling were employed to investigate the possible role the brain mineralocorticoid receptor (MR, type I) and glucocorticoid receptor (GR, type II) have in the regulation of basal and stress-induced adrenocortical secretion in the rat. The anti-mineralocorticoid and anti-glucocorticoid were administered subcutaneously (s.c.) at doses of 2.5 mg and 1.0 mg/100 g body weight, respectively. Both antagonists were also given intracerebro-ventricularly (i.c.v.) at a dose of 100 ng/rat. Under basal non-stressed conditions (at the diurnal trough in the morning), injections of either saline, anti-glucocorticoid (s.c. or i.c.v.) or anti-mineralocorticoid (s.c.) did not have effect on the plasma corticosterone level. The anti-mineralocorticoid given intracerebroventricularly, however, caused an elevation of plasma corticosterone up to 60 min after the injection. Exposure of the rats to a novel environment resulted in a large increase in the plasma corticosterone level, which was slightly reduced in the rats treated with the anti-glucocorticoid. In vehicle-treated rats, the level returned to basal values at 90 min, while in the anti-glucocorticoid- and anti-mineralocorticoid-treated groups, it remained elevated for prolonged periods. The present study thus shows that (1) the anti-glucocorticoid RU38486 via the brain GR has no effect on the basal plasma corticosterone level in the morning but interferes with a glucocorticoid negative feedback following stress and (2) the anti-mineralocorticoid RU28318 via the brain MR elevates the basal plasma corticosterone level and enhances adrenocortical secretion following stress. Accordingly, both antagonists caused prolonged adrenocortical secretion following stress. Such an effect caused by the anti-mineralocorticoid is probably due to an enhanced stress responsiveness resulting from a blockade of the limbic MR and that caused by the anti-glucocorticoid resulting from a blockade of GR involved in the termination of the stress response.
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© 1989 S. Karger AG, Basel
1989
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