title: Kidney transcriptome reveals altered steroid homeostasis in NaS1 sulfate transporter null mice.
abstract: 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 (>or=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 ( approximately 50% decrease), dehydroepiandrosterone (DHEA, approximately 30% decrease) and DHEA-sulfate ( approximately 40% decrease), and increased urinary corticosterone ( approximately 16-fold increase) and DHEA ( approximately 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.
authors.affiliation: School of Biomedical Sciences, University of Queensland, St. Lucia, QLD, Australia. paul.dawson@uq.edu.au
authors.forename: Paul Anthony
authors.initials: PA
authors.lastname: Dawson
authors.forename: Brooke
authors.initials: B
authors.lastname: Gardiner
authors.forename: Soohyun
authors.initials: S
authors.lastname: Lee
authors.forename: Sean
authors.initials: S
authors.lastname: Grimmond
authors.forename: Daniel
authors.initials: D
authors.lastname: Markovich
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics*; D003345:Corticosterone / Q000097:blood / Q000652:urine; D003687:Dehydroepiandrosterone / Q000097:blood / Q000652:urine; D005260:Female; D020869:Gene Expression Profiling; D006706:Homeostasis; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000077003:Sodium Sulfate Cotransporter; D013256:Steroids / Q000378:metabolism*; D027981:Symporters / Q000235:genetics*
chemical_list: D027682:Cation Transport Proteins; D000077003:Sodium Sulfate Cotransporter; D013256:Steroids; D027981:Symporters; D003687:Dehydroepiandrosterone; D003345:Corticosterone