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This version published online on April 17, 2003
Endocrinology, doi:10.1210/en.2003-0109
A more recent version of this article appeared on August 1, 2003
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Submitted on January 22, 2003
Accepted on April 9, 2003

Regulation of Aldosterone Synthase Gene Expression in the Rat Adrenal Gland and Central Nervous System by Sodium and Angiotensin II

Ping Ye1, Christopher J Kenyon1, Scott M MacKenzie1, Jonathan R Seckl1, Robert Fraser1, John MC Connell1, and Eleanor Davies1*

1 MRC Blood Pressure Group, Division of Cardiovascular & Medical Sciences, Western Infirmary, Glasgow, United Kingdom, G11 6NT and Molecular Endocrinology, Molecular Medicine Centre, Western General Hospital, Edinburgh, United Kingdom, EH4 2XU.

* To whom correspondence should be addressed. E-mail: ed18g{at}clinmed.gla.ac.uk.

We have developed a highly sensitive quantitative RT-PCR method for the measurement of CYP11B1 (11{beta}-hydroxylase) and CYP11B2 (aldosterone synthase) mRNAs to study their expression in the rat brain in response to dietary sodium manipulation and AngII infusion.

Male WKY rats (n = 6) were fed normal, high or low sodium diets for 12 days or were administered AngII or vehicle for 7 days. CYP11B2 and CYP11B1 expression were measured in RNA from adrenal gland and discrete brain regions using real-time quantitative RT-PCR. Sodium restriction increased adrenal CYP11B2 expression 57-fold from 1.0 x 105 ± 0.6 x 105 to 57 x 105 ± 22 x 105 copies/µg RNA (mean±SEM, P < 0.05), in the hippocampus 14-fold from 5.4 x 102 ± 0.8 x 102 to 74 x 102 ± 31 x 102 copies/µg RNA (P < 0.05) and in the cerebellum 5-fold from 1.9 x 103 ± 0.7 x 103 to 9.9 x 103 ± 3.0 x 103 copies/µg RNA (P < 0.01). CYP11B2 gene expression in the brain stem and hypothalamus was not affected. High sodium diet reduced adrenal CYP11B2 expression to 0.19 x 105 ± 0.1 x 105 copies/µg RNA (P < 0.05) but did not affect CNS expression significantly. AngII significantly increased adrenal CYP11B2 expression but did not affect CNS expression. Brain CYP11B1 mRNA levels were 10-1000-fold higher than CYP11B2 but were unaffected by dietary sodium or AngII.

To summarize, we have identified a local CYP11B2 response to sodium depletion in the hippocampus and cerebellum. This is the first such regulation of CYP11B2 transcription to be identified in the CNS.


Key words: 11{beta}-hydroxylase • aldosterone synthase • real-time quantitative RT-PCR • LightCycler







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