Aldosterone is synthesized acutely upon stimulation of the renin-angiotensin-aldosterone system from the cells of the zona glomerulosa. Several enzymes are involved in this steroidogenic process including the steroidogenic acute regulatory protein (StAR), P450 side chain cleavage enzyme (Cyp11a1) and aldosterone synthase, the product of the gene Cyp11b2.
We investigated the short time transcriptional regulation of these genes in wild type mice at 10 min intervals for one hour following application of angiotensin II (ANGII) and sodium chloride in comparison to sham injections. The aldosterone response after each stimulus was quantified through measurement by a fluorescent immunoassay. Using Real-Time PCR a fast upregulation of adrenal Cyp11b2 expression (53±5% increase over baseline expression; P<0.05) could be observed 10 min after sham injection which was accompanied by a transient increase in aldosterone secretion (baseline, 88±10 pg/ml vs 10 min, 228±23 pg/ml; P<0.005) while StAR (20 min, 233%±47%; P<0.05) and Cyp11a1 (20 min, 363%±31%; P<0.001) upregulation was delayed and more sustained. ANGII caused an increase of StAR and Cyp11a1 expression similar to that observed after sham injection while Cyp11b2 upregulation was more pronounced (10 min, 236±39%) and reflected ANGII induced stimulation of aldosterone output. Sodium challenge was followed by a sustained reduction of all three genes examined (Cyp11b2 20 min, −63±6%) which was accompanied by significant suppression of aldosterone secretion detectable after 60 min. These data suggest that acute regulation of aldosterone synthesis is accompanied by fast transcriptional modulation of steroidogenic enzymes. Parallel changes of Cyp11b2 and aldosterone levels are in line with the concept of Cyp11b2 being a rate limiting step for aldosterone output.
25 - 29 Apr 2009
European Society of Endocrinology