Adrenocortical cholesterol uptake and transport system

The adrenocortical cholesterol uptake and transport system is a specialized functional pathway in the adrenal cortex responsible for providing the essential cholesterol precursor required for steroid hormone biosynthesis. This system involves the acquisition of cholesterol from circulating lipoproteins, primarily through the scavenger receptor class B member 1 (SR-B1) for high-density lipoprotein (HDL) and the low-density lipoprotein receptor (LDLR) for LDL, as well as the mobilization of stored cholesteryl esters from lipid droplets (Hoekstra et al., 2009; JCI, 2002). The rate-limiting step of this system is the transport of cholesterol from the outer to the inner mitochondrial membrane, a process mediated by the steroidogenic acute regulatory (StAR) protein (Stocco, 2001; Wikipedia). Once inside the inner mitochondrial membrane, cholesterol is converted into pregnenolone by the cytochrome P450 side-chain cleavage enzyme (CYP11A1), initiating the steroidogenic cascade. Dysregulation of this system is central to several endocrine disorders; for instance, mutations in the StAR gene cause congenital lipoid adrenal hyperplasia, a severe condition characterized by a failure to produce any steroid hormones (Maharaj et al., 2023). In clinical practice, the system is targeted by adrenolytic drugs like mitotane, which disrupts mitochondrial function and steroidogenesis in the treatment of adrenocortical carcinoma, and by inhibitors like aminoglutethimide (Cambridge University Press). Additionally, the system's activity is utilized for diagnostic purposes through adrenal scintigraphy using radiolabeled cholesterol analogs such as 6β-iodomethyl-19-norcholesterol (NP-59), which serves as a functional marker of adrenocortical cholesterol uptake (SNM Journals; Cambridge University Press).

Other names

Adrenal cholesterol trafficking systemSteroidogenic cholesterol uptake pathwayAdrenocortical cholesterol metabolism system

Inhibition of cholesterol uptake or intramitochondrial transport to reduce steroid hormone synthesis; or selective uptake of radiolabeled cholesterol analogs for diagnostic imaging of adrenal function.