Question: 

Male-dominant and testosterone-dependent expression of Oat1 and Oat3, which are involved in the transport of organic anions across the cell membrane, have been shown in rat renal proximal tubule cells. The aim of this study was to identify the transcriptional regulators of sex-dependent Oat1 and Oat3 expression.

Methodology: 

The activities of Oat1 and Oat3 promoter constructs were investigated using luciferase assays. Expression profiling was done using SurePrint G3 rat GE 8x60K microarray. RNA was isolated from renal cortical slices of four adult rats per sex. The genes which are expressed in the proximal tubule cells were filtered using a transcriptome database.

Result: 

Our results revealed that predicted androgen response elements in the promoter regions of Oat1 and Oat3 are not functional, and that both transporters are not directly activated by the classical androgen receptor mediated transcriptional pathway. Microarray screening revealed as potential transcriptional regulators amongst other, male-dominant genes B-cell lymphoma 6 (Bcl6), polymerase (RNA) III (DNA-directed) polypeptide G (32kD) and hydroxysteroid (17-beta) dehydrogenase 1. The transcription factor Bcl6 activated the promoters of Oat1 and Oat3.

Conclusion: 

The renal male-dominant expression of Oat1 and Oat3 appears to be directly regulated by transcription factor Bcl6 and not by classical androgen receptor mediated pathway.

(Supported by: DFG-Bu571/8-1)