Regulated expression of the prostacyclin receptor (IP) gene by androgens within the vasculature: Combined role for androgens and serum cholesterol.

摘要: The prostanoid prostacyclin plays a key cardioprotective role within the vasculature. There is increasing evidence that androgens may also confer cardioprotection but through unknown mechanisms. This study investigated whether androgen dihydrotestosterone (DHT) regulate expression of prostacyclin/I receptor or, in short, IP platelet-progenitor megakaryoblastic and vascular endothelial cells. DHT significantly increased mRNA protein expression, IP-induced cAMP generation promoter (PrmIP)-directed gene all cell types examined. androgen-responsive region was localised to cis-acting response element (ARE), which lies close proximity functional sterol (SRE) core promoter. In normal serum conditions, classic (AR) binding ARE PrmIP. However, under conditions low-cholesterol, led further increases an indirect mechanism involving AR-dependent upregulation SCAP enhanced SREBP1 processing & SRE Chromatin immunoprecipitation assays confirmed DHT-induced AR vivo cells cultured while, low cholesterol, elements, respectively, PrmIP resulting expression. Collectively, these data establish human transcriptional regulation DHT, where this influenced by serum-cholesterol levels. explain, part, some protective actions