The DOI matches its Crossref record; 99 of the 99 references it cites were found in a registry or an index.
Early steps in steroidogenesis: intracellular cholesterol trafficking
Open accessAbstract
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.
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Cites
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Cited by
MAM (mitochondria-associated membranes) in mammalian cells: Lipids and beyond
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Steroidogenesis in the skin: Implications for local immune functions
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Novel activities of CYP11A1 and their potential physiological significance
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Metadata
- Authors
- Miller, W. L., & Bose, H. S.
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2011-12
- Volume
- 52
- Issue
- 12
- Pages
- 2111-2135
- ISSN
- 0022-2275 (ISSN-L)
- OpenAlex
- W1963827257
- Cited by
- 554
- References
- 99
- FWCI
- 28.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
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