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This version published online on September 22, 2005
Endocrinology, doi:10.1210/en.2005-0370
A more recent version of this article appeared on December 1, 2005
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Submitted on March 30, 2005
Accepted on September 12, 2005

The aldosterone synthase (CYP11B2) and 11{beta}-hydroxylase (CYP11B1) genes are not expressed in the rat heart

P Ye, C J Kenyon, S M MacKenzie, A S Jong, C Miller, G A Gray, A Wallace, A S Ryding, J J Mullins, M W McBride, D Graham, R Fraser, J MC Connell, and E Davies*

PY, SMM, ASJ, CM, MWM, DG, RF, JMCC and ED., Division of Cardiovascular and Medical Sciences, Western Infirmary, Church Street, Glasgow G11 6NT, United Kingdom.; CJK. Molecular Endocrinology, Molecular Medicine Centre, Western General Hospital, Edinburgh, EH4 2XU, United Kingdom.; GAG, AW. Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH8 9J2, United Kingdom.; ASR, JJM. Molecular Physiology Laboratory, Wilkie Building, Teviot Place, University of Edinburgh Medical School, Edinburgh EH8 9AG, United Kingdom

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

Aldosterone synthase (CYP11B2) and 11{beta}-hydroxylase (CYP11B1) catalyze the production of aldosterone and corticosterone, respectively, in the rat adrenal cortex. Recently, there has been some debate as to whether these corticosteroids are also produced in the hearts of rodents and humans, possibly contributing to the development of hypertrophy and myocardial fibrosis. To investigate this, we have used our established, highly-sensitive real-time quantitative RT-PCR method to measure CYP11B1 and CYP11B2 mRNA levels in adrenal and cardiac tissue from several rat models of cardiovascular pathology. We have also studied isolated adult rat ventricular myocytes treated with Ang II and ACTH.

Total RNA was isolated from the adrenal and cardiac tissue of (i) male Wistar rats with heart failure (CHF) induced by coronary artery ligation (CAL) and sham-operated controls; (ii) stroke prone spontaneously hypertensive rats (SHRSP) and WKY controls; (iii) cyp1a1Ren-2 transgenic rats (TG) and Fischer controls; (iv) isolated adult Sprague Dawley ventricular myocytes incubated with DOC, DOC + AngII, or DOC + ACTH.

Adrenal CYP11B2 expression was significantly increased in TG compared with Fischer controls (1.3x109± 1.2x109 vs. 2.1x107± 7.0x106 copies/µg RNA, P < 0.05). There were no other significant differences in adrenal CYP11B2 or CYP11B1 expression between the model animals and their respective controls. Cardiac CYP11B1 and CYP11B2 mRNA transcript levels from all in vivo and in vitro groups, were never greater than 102 copies per µg total RNA and therefore too low to be detected reproducibly. This suggests that cardiac corticosteroid production is unlikely to be of any physiological or pathological significance.
Key words: aldosterone • hypertension • cardiac hypertrophy • cardiac fibrosis • 11{beta}-hydroxylase • aldosterone synthase • real-time quantitative RT-PCR




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