Endocrine Abstracts

Aldosterone synthase catalyses the synthesis of aldosterone in the adrenal cortex and is encoded by the CYP11B2 gene. Recent studies have shown that CYP11B2 is also expressed in the central nervous system (CNS) but little is known about its regulation. In this study, we have quantitated CYP11B2 expression in the CNS following dietary manipulation of sodium and infusion of angiotensin II.
In study 1, 3 groups of male WKY rats (n=6) were fed normal (0.3%), high (3%) or low (0.03%) sodium diets for 12 days. In study 2, 2 groups of animals (n=6) received vehicle or angiotensin II (200ng/kg/min) via an osmotic mini-pump for 7 days. RNA was isolated and CYP11B2 expression was measured using real-time quantitative RT-PCR(LightCycler).
Low sodium increased CYP11B2 expression in the adrenal gland from 1.6x10⁵ plus/minus1.2x10⁵ to 5.9x10⁶ plus/minus 2.6x10⁶copies/micrograms RNA (Mean plus/minus SEM, p<0.001), in the hippocampus from 7.0x10² plus/minus 1.3x10² to 6.0x10³ plus/minus 2.9x10² copies/micrograms RNA (p=0.005) and in the cerebellum from 1.6x10³ plus/minus 2.9x10² to 9.5x10³ plus/minus 2.3x10³copies/micrograms RNA (p<0.001). Low sodium had no significant effect on CYP11B2 gene expression in the brain stem or hypothalamus. High sodium decreased CYP11B2 expression in the adrenal gland to 4.0x10⁴plus/minus 2.7x10⁴ copies/micrograms RNA (p=0.02), but had no effect on CNS tissue. Plasma aldosterone levels were 308 plus/minus 52, 134 plus/minus 19 and 154 plus/minus 50 pM in the low, normal and high sodium groups respectively. Angiotensin II increased CYP11B2 expression in the adrenal gland from 2.7x10⁶ plus/minus 8.7x10⁵ to 1.7x10⁷ plus/minus 6.5x10⁶copies/micrograms RNA (p=0.03) but had no significant effect on CYP11B2 expression in the CNS. Plasma aldosterone increased from 414 plus/minus 50pM to 671 plus/minus 182pM.
The results suggest that CYP11B2 expression may be under the regulation of the renin angiotensin system in some, but not all, regions of the CNS.