ABSTRACT
It is hypothesized that hyperuricemia in males is caused by androgen-induced urate reabsorptive transport system in the kidney. The expression of urate transporter 1 (Urat1), sodium-coupled monocarboxylate transporter 1 (Smct1) and glucose transporter 9 (Glut9) were investigated in orchiectomized mice with or without testosterone replacement. Testosterone enhanced mRNA and protein levels of Smct1 while those of Glut9 were attenuated. Although the mRNA level of Urat1 was enhanced by testosterone, the corresponding levels of Urat1 protein remained unaffected. Thus, the induction of Smct1 by testosterone is a candidate mechanism underlying hyperuricemia in males.
Subject(s)
Kidney/drug effects , Kidney/metabolism , Testosterone/pharmacology , Uric Acid/metabolism , Animals , Biological Transport/drug effects , Case-Control Studies , Glucose Transport Proteins, Facilitative/genetics , Glucose Transport Proteins, Facilitative/metabolism , Hyperuricemia/metabolism , Hyperuricemia/physiopathology , Kidney/physiology , Male , Mice , Mice, Inbred ICR , Monocarboxylic Acid Transporters/genetics , Monocarboxylic Acid Transporters/metabolism , Orchiectomy , Organic Anion Transporters/genetics , Organic Anion Transporters/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Symporters/genetics , Symporters/metabolism , Uric Acid/blood , Uric Acid/urineABSTRACT
In order to elucidate the mechanisms of post-exercise acute renal failure, one of the complications of hereditary renal hypouricemia, we have targeted the mouse Slc22a12 gene by the exchange of exons 1-4 with pMC1neo-polyA. The knockout mice revealed no gross anomalies. The concentration ratio of urinary urate/creatinine of the knockout mice was significantly higher than that of wildtype mice, indicating an attenuated renal reabsorption of urate. The plasma levels of urate were around 11 muM and were similar among the genotypes. Although the fractional excretion of urate of knockout mice was tend to higher than that of wildtype mice, the urate reabsorption ability remained in the kidney of knockout mice, indicating a urate reabsorptive transporter other than Urat1.
