StAR is the acronym for Steroidogenic Acute Regulatory protein, a vital transport protein that mediates the rate-limiting step in the biosynthesis of all steroid hormones, including cortisol, aldosterone, testosterone, and estrogen. Its primary function is to facilitate the rapid transfer of cholesterol, the universal precursor molecule, from the outer mitochondrial membrane to the inner mitochondrial membrane within steroid-producing cells. StAR activity is the key point of acute regulation for the entire steroidogenesis pathway.
Origin
The protein was discovered in the early 1990s through research into the acute regulation of steroid hormone production by trophic hormones like ACTH and LH. Its name reflects its function: it is ‘Steroidogenic’ because it initiates steroid synthesis, ‘Acute’ because its expression and activity are rapidly regulated, and ‘Regulatory’ because it controls the flux of cholesterol. The discovery of StAR provided the molecular explanation for the rapid, on-demand secretion of steroid hormones.
Mechanism
The mechanism begins with the binding of a trophic hormone (e.g., LH or ACTH) to its cell-surface receptor, which typically activates the cAMP second messenger system. This signaling cascade induces the rapid synthesis and phosphorylation of the StAR protein. StAR then acts at the outer mitochondrial membrane to promote the movement of cholesterol across the intermembrane space to the inner membrane. Once inside the inner membrane, the cholesterol is immediately converted to pregnenolone by the P450scc enzyme, initiating the subsequent cascade of steroid hormone synthesis.
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