Regulation of CYP enzymes in steroidogenesis with particular focus on cholesterol metabolism and vitamin D-related processes

摘要

Our studies concern CYP enzymes in steroidogenesis. We are especially interested in key enzymes in cholesterol metabolism, vitamin D bioactivation and adrenal steroidogenesis. These processes are tightly controlled by a number of factors. We have investigated how hormones and certain drugs influence these processes by regulation of key enzymatic steps.CYP27A1 is an enzyme essential for cholesterol homeostasis and is considered an anti-atherogenic enzyme. CYP27A1 is required in bile acid biosynthesis and participates in oxysterol formation, cholesterol transport and cholesterol elimination (Fig 1). Considering these important functions, mechanisms for regulation of the human CYP27A1 gene are of great interest (1). CYP27A1 is also a vitamin D 25-hydro-xylase, catalyzing the first step in the bioactivation of vitamin D into the multifunctional hormone 1,25-dihydroxyvitamin D. Fig 2 shows the bioactivation of vitamin D. Multiple vitamin D 25-hydroxylases exist in humans. In addition to CYP27A1, other known vitamin D 25-hydroxylases are CYP2R1, CYP2J2 and CYP3A4 (2). The active 1,25-dihydroxyvitamin D is a calcium-regulating hormone. Newly discovered functions of this hormone are regulation of cell growth, regulation of immune function and regulation of blood pressure and insulin production. In the current presentation, we focus on our recent studies on the regulation of CYP27A1 and the CYP enzymes catalyzing the first step in the bioactivation of vitamin D.