Short term regulation of aldosterone secretion after stimulation and suppression experiments in mice

Abstract

Aldosterone is synthesized acutely from the zona glomerulosa cells upon stimulation by the renin-angiotensin-aldosterone system. Several enzymes are involved in this steroidogenic process including the steroidogenic acute regulatory protein (StAR), P450 side chain cleavage enzyme (Cyp11a1), and aldosterone synthase (Cyp11b2) which has been demonstrated to be transcriptionally regulated by the nuclear transcription factors NGF1-B and Nurr1. We investigated the short time transcriptional regulation of these genes in wild-type mice at 10 min intervals for 1 h following application of 0.2 nmol angiotensin II (ANGII) or sodium chloride in comparison sham injections. Using real-time PCR a fast upregulation of adrenal Cyp11b2 expression (53+/-5% increase over baseline) could be observed 10 min after sham injection which was accompanied by a transient increase in aldosterone secretion while StAR and Cyp11a1 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 a significant suppression of aldosterone secretion detectable after 60 min. While increases in NGF1-B mRNA levels were similar between the treatment groups, Nurr1 expression levels were induced only upon ANGII administration. These data suggest that acute regulation of aldosterone synthesis is accompanied by fast transcriptional modulation of steroidogenic enzymes and transcription factors that are likely to be involved in aldosterone secretion.