Sex steroid regulation and identification of different transcription units of the SA gene in mouse kidney.

Although the SA gene was first identified as a putative candidate gene to understand the molecular basis of hypertension in rat and humans, the concept has not been supported in recently generated SA-null mice. We had first identified the mouse SA gene on the basis of its strong androgenic regulation in mouse kidney and further characterized its genomic organization, transcription start site and chromosomal location. Northern blot, RT-PCR and in situ hybridization assays determined mouse strain, tissue distribution, sex-hormone dependence and cell expression of the SA) mRNA. Kidney and liver constitute the main expression sites of the SA gene; in particular it is expressed in epithelial proximal tubule cells in the presence of androgens. This androgen-dependent expression is abrogated when estrogens are also present. By using the sensitive RT-PCR technique, minor SA expression sites, corresponding to testes, stomach, heart and lung, have also appeared. Like in kidney, expression of the SA gene in heart and lung is androgen-dependent. Production of rabbit antibodies against SA-synthetic peptides identified the SA protein, a moiety of unknown function, which has been defined as a member of the acyl-CoA synthetase family. We have determined that the SA protein follows the same distribution and regulation as its corresponding mRNA. Transient transfection assays followed by confocal microscopy identified the mitochondria of proximal tubule-derived PCT3 cells as the subcellular location of the SA protein. Different transcriptional units produced by splicing events, occurring before the translation initiation site, have been identified from mouse kidney. This work provides the basis to further understand the molecular mechanisms that control the sex-steroid-dependent expression of the SA gene in mouse kidney, heart and lung, where SA is also expressed in an androgen-dependent manner.

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