Steroidogenic acute regulatory protein: an update on its regulation and mechanism of action

Arch Med Res. Nov-Dec 2001;32(6):576-86. doi: 10.1016/s0188-4409(01)00338-1.


Steroidogenic acute regulatory (StAR) protein controls the rate-limiting step in steroidogenesis: the transport of cholesterol from the outer to the inner mitochondrial membrane. Early studies indicated that rate of transcription of the StAR gene is a primary determinant of steroidogenesis. The transcription factors that govern basal and cAMP-dependent StAR expression are reviewed, as are new findings regarding chromatin modifications associated with activation of the StAR promoter. Molecular genetic studies of congenital lipoid adrenal hyperplasia, a rare disease caused by mutations in the StAR gene, and structure-function studies defined two major domains within the StAR protein, the N-terminal mitochondrial targeting sequence and the C-terminal StAR-related lipid transfer (START) domain, which promotes the translocation of cholesterol between the two mitochondrial membranes. Several models of StAR's mechanism of action have been proposed based on a combination of structure/function studies or on the crystal structure of a related START domain. The models-intermembrane shuttle hypothesis, and cholesterol desorption hypothesis-are discussed with respect to the known biochemical and biophysical events associated with steroidogenesis and the structure of StAR.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Acetylation
  • Adrenal Hyperplasia, Congenital / classification
  • Adrenal Hyperplasia, Congenital / genetics
  • Animals
  • Base Sequence
  • Biological Transport
  • Carrier Proteins*
  • Cholesterol / metabolism*
  • Female
  • Gene Expression Regulation
  • Histones / metabolism
  • Humans
  • Intracellular Membranes / metabolism
  • Lipid Metabolism
  • Male
  • Membrane Lipids / metabolism
  • Membrane Proteins / chemistry
  • Membrane Proteins / physiology
  • Mice
  • Mice, Knockout
  • Mitochondria / metabolism
  • Models, Biological
  • Molecular Sequence Data
  • Phenotype
  • Phosphoproteins / chemistry
  • Phosphoproteins / deficiency
  • Phosphoproteins / genetics
  • Phosphoproteins / physiology*
  • Phosphorylation
  • Promoter Regions, Genetic
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / physiology
  • Sequence Alignment
  • Sequence Deletion
  • Sequence Homology, Nucleic Acid
  • Steroids / biosynthesis*
  • Structure-Activity Relationship
  • Transcription, Genetic


  • Carrier Proteins
  • Histones
  • Membrane Lipids
  • Membrane Proteins
  • Phosphoproteins
  • Recombinant Fusion Proteins
  • STARD3 protein, human
  • Steroids
  • steroidogenic acute regulatory protein
  • Cholesterol