Decreased hypothalamic and adrenal angiotensin II receptor expression and adrenomedullary catecholamines in transgenic mice with impaired glucocorticoid receptor function

Document Type

Journal Article

Publication Date

12-1-2004

Journal

Neuroendocrinology

Volume

80

Issue

3

DOI

10.1159/000082358

Keywords

Adrenal medulla; Adrenal steroids; Angiotensin receptors; Catecholamines; Corticotropin-releasing hormone; Median eminence; Paraventricular nucleus; Supraoptic nucleus; Transgenic mice; Tyrosine hydroxylase; Vasopressin

Abstract

In transgenic mice expressing an antisense mRNA against the glucocorticoid receptor (GR), which partially blocks GR expression, impaired glucocorticoid feedback efficacy is accompanied by reduced hypothalamic corticotropin-releasing hormone (CRH) and vasopressin (AVP) activity and reduced peripheral sympathetic tone, indications of a shift in the balance of hypothalamic CRH and sympathetic regulation. As angiotensin II (Ang II) regulates CRH, AVP and sympathetic activity, we studied the expression of Ang II receptors in the hypothalamus and adrenal gland of GR transgenic and wild-type mice, adrenal catecholamines and mRNA for their rate-limiting enzyme, tyrosine hydroxylase (TH). We found that transgenic mice expressed significantly less numbers of Ang II AT1 receptors in the hypothalamic paraventricular nucleus and median eminence, lower numbers of AT2 receptors in supraoptic and paraventricular nuclei and lower numbers of AT2 receptors in the adrenal medulla when compared with wild-type controls. The expression of TH mRNA and the concentration of adrenomedullary epinephrine and norepinephrine were also lower in transgenic mice when compared with wild-type controls. Decreased hypothalamic and adrenal Ang II receptor stimulation as a result of decreased GR expression may explain the decreased hypothalamic CRH and AVP and decreased adrenomedullary and sympathetic activities in this model. Copyright © 2004 S. Karger AG, Basel.

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