Endocrine Abstracts

A genome-wide association study indicated a correlation between a locus at 5q32 and high aldosterone to renin ratio in subjects from KORA F4 survey. As we considered the genes in this locus for their potential relevance for the etiology of primary aldosteronism, we observed significantly higher expression of one of them, SLC26A2, in mouse adrenal glands, even though the gene’s function in the adrenal was not reported in the literature. Using the human adrenocortical cell line NCI H295r and wt mice, effects of aldosterone regulators on SLC26A2 gene expression were evaluated. Consistently, angiotensin II treatment resulted in a decrease in SLC26A2 gene expression in vitro and in vivo, while potassium resulted in lower expression levels only in the in vivo setting. Interestingly, a shRNA-mediated four-fold knockdown of SLC26A2 in H295r cells yielded a significant increase in aldosterone synthase (CYP11B2) expression and aldosterone output of the cells; this effect of knockdown was sustained after incubation with aldosterone stimulators including potassium, angiotensin or forskolin. An increase in the expression of calcium dependent regulators of CYP11B2 expression including CamK1, NR4A1 and NR4A2 was observed. In order to gain insight into in vivo functional characteristics of the gene, we analyzed gene expression profiles in adrenal glands from SLC26A2 knock-out mice. These results suggested a tendency towards higher expression for adrenal enzymes with more specific role in aldosterone synthesis and expression in the zona glomerulosa (CYP11B2, HSD3B6), and a tendency towards lower expression for enzymes with a more unspecified expression pattern (STAR, CYP11A1) or a more fasciculata specific distribution (HSD3B1). Further detailed investigation into the functional link between adrenal SLC26A2 expression and aldosterone production is ongoing.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.