Related Experiment Video
Updated: May 28, 2026

Enrichment of Mammalian Tissues and Xenopus Oocytes with Cholesterol
Published on: March 25, 2020
Early steps in steroidogenesis: intracellular cholesterol trafficking
Walter L Miller1, Himangshu S Bose2
1Department of Pediatrics, School of Medicine, University of California, San Francisco, CA 94143; UCSF Benioff Children's Hospital, San Francisco, CA 94143.
Abstract:
Steroid hormones are made from cholesterol, primarily derived from lipoproteins that enter cells via receptor-mediated endocytosis. In endo-lysosomes, cholesterol is released from cholesterol esters by lysosomal acid lipase (LAL; disordered in Wolman disease) and exported via Niemann-Pick type C (NPC) proteins (disordered in NPC disease). These diseases are characterized by accumulated cholesterol and cholesterol esters in most cell types. Mechanisms for trans-cytoplasmic cholesterol transport, membrane insertion, and retrieval from membranes are less clear. Cholesterol esters and "free" cholesterol are enzymatically interconverted in lipid droplets. Cholesterol transport to the cholesterol-poor outer mitochondrial membrane (OMM) appears to involve cholesterol transport proteins. Cytochrome P450scc (CYP11A1) then initiates steroidogenesis by converting cholesterol to pregnenolone on the inner mitochondrial membrane (IMM). Acute steroidogenic responses are regulated by cholesterol delivery from OMM to IMM, triggered by the steroidogenic acute regulatory protein (StAR). Chronic steroidogenic capacity is determined by CYP11A1 gene transcription. StAR mutations cause congenital lipoid adrenal hyperplasia, with absent steroidogenesis, potentially lethal salt loss, and 46,XY sex reversal. StAR mutations initially destroy most, but not all steroidogenesis; low levels of StAR-independent steroidogenesis are lost later due to cellular damage, explaining the clinical findings. Rare P450scc mutations cause a similar syndrome. This review addresses these early steps in steroid biosynthesis.
Related Concept Videos
Overview of Fatty Acid Metabolism
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...
Cholesterol: Significance and Regulation
Considering cholesterol and...
Synthesis of Phosphatidylcholine in the ER Membrane
The major components of all eukaryotic cell...
Protein Transport to the Inner Chloroplast Membrane
Regulation of Nuclear Protein Sorting
Intracellular Hormone Receptors

