| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1992861 | The Journal of Steroid Biochemistry and Molecular Biology | 2008 | 8 Pages |
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.
