The role of secretin in regulating aldosterone synthase expression in mouse

Abstract

Water and salt homeostasis is tightly controlled by both central and peripheral mechanisms. Angiotensin II (ANGII) and Vasopressin (VP) have long been known to be essential in this regulatory process. Recent studies have found that secretin (SCT) can regulate water homeostasis by playing osmoregulatory functions redundant as ANGII to stimulate VP expression and release in the hypothalamus. However, the functional role of secretin in salt homeostasis, which is closely related to water homeostasis, remains unclear. This study therefore aims to investigate the modulating function of secretin in the synthesis of aldosterone, which is known to be critical in salt regulation.

Using immunohistochemical staining, expression of secretin receptor (SCTR) was detected in the zona glumerulosa of adrenal cortex. In mouse adrenal gland, real time quantitative polymerase chain reaction showed that both intraperitoneal (IP) and intracerebral ventricular (ICV) injections of SCT significantly increased aldosterone synthase (cyp11b2) expression levels. This effect was determined to be secretin-specific as it is not observed in SCTR knockout (SCTR-/-) mice. The increase of aldosterone synthase expression levels was further confirmed by Western blot analysis. In circulation, the serum level of aldosterone was also increased by ICV SCT injection, supporting the activation of aldosterone synthase by both central and peripheral SCT. Further studies showed the ICV-SCT induced aldosterone synthase can be significantly reduced by conivaptan, a VP receptor antagonist, indicating that the stimulatory effect of SCT on aldosterone synthesis is VP-related. In low sodium diet-fed mice, both SCTR and aldosterone synthase expression level were significantly increased and elevated serum SCT level was also observed. Western blot analysis also found an increase in aldosterone synthase expression in wild type mice but not in SCTR-/- controls. These results warrant the further study of the role of SCT in sodium retention.

In summary, SCT facilitates the synthesis of aldosterone through the up-regulation of aldosterone synthase. This effect can be triggered by both central and peripheral administration of SCT. The central effect of SCT on aldosterone synthesis is vasopressin-related. SCT may also participate in the sodium retention under low-salt conditions. Taken together, this study suggests a potential function of SCT in regulating body sodium homeostasis.