Steroidogenic acute regulatory protein (StAR)

Steroidogenic acute regulatory protein (StAR, also known as STARD1) is a mitochondrial transport protein primarily expressed in steroid-producing cells such as those in the adrenal cortex, ovary, and testis. StAR mediates the rate-limiting step in steroid hormone biosynthesis by facilitating the transfer of cholesterol from the outer to the inner mitochondrial membrane, where cholesterol is cleaved by cytochrome P450scc (CYP11A1) to form pregnenolone, the precursor to all steroid hormones. StAR contains an N-terminal mitochondrial targeting sequence and a C-terminal START (StAR-related lipid transfer) domain, which binds cholesterol. Mutations in the StAR gene cause congenital lipoid adrenal hyperplasia, a severe disorder of adrenal and gonadal steroid production. StAR expression is regulated by trophic hormones (e.g., ACTH, LH) and is modulated in response to cAMP and other signaling pathways. While no approved drugs currently target StAR directly, its activity is critical for endocrine health and is sensitive to various endocrine disruptors.

Other names

STARD1START domain-containing protein 1

Agents that induce StAR increase steroidogenesis by promoting mitochondrial cholesterol transfer. Agents that inhibit StAR decrease steroidogenesis by blocking cholesterol movement to CYP11A1/P450scc.