Effects of ACTH, dexamethasone, and adrenalectomy on 11 β-hydroxylase (CYP11B1) and aldosterone synthase(CYP11B2) gene expression in the rat central nervous system

Ye, P., Kenyon, C. J., MacKenzie, S. M. , Nichol, K., Seckl, J. R., Fraser, R., Connell, J. M.C. and Davies, E. (2008) Effects of ACTH, dexamethasone, and adrenalectomy on 11 β-hydroxylase (CYP11B1) and aldosterone synthase(CYP11B2) gene expression in the rat central nervous system. Journal of Endocrinology, 196(2), pp. 305-311. (doi:10.1677/JOE-07-0439)

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Publisher's URL: http://dx.doi.org/10.1677/JOE-07-0439

Abstract

Using a highly sensitive quantitative RT-PCR method for the measurement of CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) mRNAs, we previously demonstrated that CYP11B2 expression in the central nervous system (CNS) is subject to regulation by dietary sodium. We have now quantified the expression of these genes in the CNS of male Wistar Kyoto (WKY) rats in response to systemic ACTH infusion, dexamethasone infusion, and to adrenalectomy. CYP11B1 and CYP11B2 mRNA levels were measured in total RNA isolated from the adrenal gland and discrete brain regions using real-time quantitative RT-PCR. ACTH infusion (40 ng/day for 7 days, N=8) significantly increased CYP11B1 mRNA in the adrenal gland, hypothalamus, and cerebral cortex compared with animals infused with vehicle only. ACTH infusion decreased adrenal CYP11B2 expression but increased expression in all of the CNS regions except the cortex. Dexamethasone (10 µg/day for 7 days, N=8) reduced adrenal CYP11B1 mRNA compared with control animals but had no significant effect on either gene's expression in the CNS. Adrenalectomy (N=6 per group) significantly increased CYP11B1 expression in the hippocampus and hypothalamus and raised CYP11B2 expression in the cerebellum relative to sham-operated animals. This study confirms the transcription of CYP11B1 and CYP11B2 throughout the CNS and demonstrates that gene transcription is subject to differential regulation by ACTH and circulating corticosteroid levels.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Davies, Professor Eleanor and Connell, Professor John and MacKenzie, Dr Scott and Fraser, Prof Robert
Authors: Ye, P., Kenyon, C. J., MacKenzie, S. M., Nichol, K., Seckl, J. R., Fraser, R., Connell, J. M.C., and Davies, E.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Journal of Endocrinology
Publisher:BioScientifica Ltd.
ISSN:0022-0795
ISSN (Online):1479-6805
Published Online:12 November 2007
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
392521Regulation of aldosterone and cortisol synthesis in hypertension and cardiovascular diseaseEleanor DaviesMedical Research Council (MRC)G0400874Institute of Cardiovascular and Medical Sciences
392522Regulation of aldosterone and cortisol synthesis in hypertension and cardiovascular diseaseEleanor DaviesMedical Research Council (MRC)G0400874Institute of Cardiovascular and Medical Sciences