Kidney transcriptome reveals altered steroid homeostasis in NaS1 sulfate transporter null mice

Sulfate is essential for human growth and development, and circulating sulfate levels are maintained by the NaS1 sulfate transporter which is expressed in the kidney. Previously, we generated a NaS1-null (Nas1−/−) mouse which exhibits hyposulfatemia. In this study, we investigated the kidney transcriptome of Nas1−/− mice. We found increased (n = 25) and decreased (n = 60) mRNA levels of genes with functional roles that include sulfate transport and steroid metabolism. Corticosteroid-binding globulin was the most up-regulated gene (110% increase) in Nas1−/− mouse kidney, whereas the sulfate anion transporter-1 (Sat1) was among the most down-regulated genes (≥50% decrease). These findings led us to investigate the circulating and urinary steroid levels of Nas1−/− and Nas1+/+ mice, which revealed reduced blood levels of corticosterone (≈50% decrease), dehydroepiandrosterone (DHEA, ≈30% decrease) and DHEA-sulfate (≈40% decrease), and increased urinary corticosterone (≈16-fold increase) and DHEA (≈40% increase) levels in Nas1−/− mice. Our data suggest that NaS1 is essential for maintaining a normal metabolic state in the kidney and that loss of NaS1 function leads to reduced circulating steroid levels and increased urinary steroid excretion.