Endocrine Abstracts (2004) 7 P209

The effect of adrenalectomy on 11beta-hydroxylase(CYP11B1) and aldosterone synthase (CYP11B2) gene expression in the hippocampus

P Ye1, CJ Kenyon2, K Nichol2, SM MacKenzie1, R Fraser1, JR Seckl2, JMC Connell1 & E Davies1

1Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK; 2Molecular Medicine, Molecular Medicine Centre, University of Edinburgh, Edinburgh, UK.

11Beta-Hydroxylase and aldosterone synthase catalyse the synthesis of corticosterone and aldosterone in the rat adrenal cortex and are encoded by the CYP11B1 and CYP11B2 genes respectively. These genes are also expressed in distinct regions of the CNS and cardiovascular system where they may play a key role in behavioural response and blood pressure homeostasis. However, it is unclear whether this extra-adrenal expression is regulated by, or contributes to, circulating levels of corticosteroids. In this study, we have quantified CYP11B1 and CYP11B2 gene expression in the hippocampus following adrenalectomy.

Adrenalectomy or sham adrenalectomy was performed on 2 groups of male Wistar rats (n=6/group). After 7 days, RNA was isolated from the hippocampus. CYP11B1 and CYP11B2 expression were measured using real-time quantitative RT-PCR using a LightCycler. Fecal corticosterone and aldosterone were measured each day by RIA.

Although adrenalectomy significantly decreased fecal levels of corticosterone and aldosterone, there were still detectable levels of each steroid. Corticosterone decreased from 201.1 plus/minus 57.5 to 5.2 plus/minus 0.7 nanograms/rat/day (P<0.05) and aldosterone from 39.6 plus/minus 8.1 to 6.9 plus/minus 3.8 nanograms/rat/day over the 7 days. Adrenalectomy caused a 1.3-fold (p<0.05) increase in CYP11B1 expression in the hippocampus. CYP11B2 gene expression was unaffected.

These results show that adrenalectomy increases CYP11B1 expression in the hippocampus, a region known to express the mineralocorticoid receptor at high levels. Despite the removal of the adrenal glands, detectable levels of fecal corticosteroids remain. These may be derived from extra-adrenal steroidogenic systems not only in the hippocampus but also in other parts of the CNS and the cardiovascular system. This is currently under investigation.

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