Characteristic induction of steroidogenic factor 1 (SF-1) and DAX-1 and enhanced expression of glucocorticoid synthesis-related genes in adrenals from spontaneously hypertensive rats

Abstract

To gain insight into the molecular mechanism of hyper-glucocorticoidism in spontaneously hypertensive rats (SHR), this study investigated the expression of genes related to glucocorticoid synthesis, melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (StAR), cytochrome P450 side chain cleavage enzyme (P450scc) and 11β-hydroxylase (P450c11), and the transcription factors of steroidogenic factor 1 (SF-1), which stimulates expression of the above gene, and DAX-1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome gene 1), which negatively regulates the transcriptional activity of SF-1, in adrenals from SHR. On quantitative real time RT-PCR analysis, gene expression levels of MC2R, StAR, P450scc and P450c11 in SHR were high compared with those in normotensive Wistar Kyoto rats (WKY). The gene expression level of SF-1 was not different between the two rats. However, the expression level of DAX-1 in SHR was markedly lower than that in WKY. Furthermore, the protein levels of StAR, SF-1 and DAX-1 determined by Western blot analysis coincided well with the gene expressions in both rats. These results suggest that the low level of DAX-1 may enhance the transcriptional activity of SF-1 and expression of genes related to glucocorticoid synthesis, which are targeted by SF-1, in adrenals from SHR.