Regulation of the Steroidogenic Acute Regulatory Protein by 3 0 – 5 0 Dibutyryl Cyclic Amp and Transforming Growth Factor-Beta Dependent Pathways. Doctoral Dissertation

The steroidogenic acute regulatory (StAR)proteinmediates the rate-limiting stepofmitochondrial transport of cholesterol for steroid biosynthesis. To investigate the regulation of this protein in lower vertebrates,we cloned the StAR coding region from large-mouthbass for analysis. Induction of themRNAcorrespondedwith increasing levelsofplasmasex steroids invivo.Culturesof largemouth bass ovarian follicles were exposed to dibutyryl cAMP (dbcAMP), a potent signaling molecule for steroidogenesis. StARmRNA expression was significantly up-regulated by dbcAMP signaling, sug-gesting that the 5 regulatory region of the gene is functionally conserved. To further analyze its transcriptional regulation, a 2.9-kb portion of the promoter was cloned and transfected into Y-1 cells, a steroidogenic mouse adrenocortical cell line. The promoter activity was induced in a dose-responsive manner upon stimulation with dbcAMP; however, deletion of 1 kb from the 5 end of the promoter segment significantly diminished the transcriptional activation. A putative retinoic acid-related receptor-/rev-erb element was identified between the1.86- and2.9-kb regio