Updated: Aug 15
This article is part of the Deep Define series. These articles provide an in-depth definition and explanation of complex topics that may require further explanation to understand fully.
StAR (STARD1), or steroidogenic acute regulatory protein, is a transport protein that controls cholesterol transfer inside the mitochondria, which is the rate-limiting step in steroid hormone synthesis.
It's mostly found in steroid-producing cells, such as theca and luteal cells in the ovary, Leydig cells in the testis, and adrenal cortex cell types.
It is greatly involved in the production of steroids and hormones, such as testosterone, etc.
Effects on the Body
The lack of functioning StAR in humans and mice drastically decreases steroid production, although it does not completely eradicate it. Steroids include all steroid hormones, such as testosterone, DHT, etc.
Other effects on the body are not yet fully understood, though they include the following.
Bile Acid Production: StAR may potentially transport cholesterol to sterol 27-hydroxylase, a second mitochondrial enzyme. It might be necessary for the initial step in one of the two routes for the liver to produce bile acids.
Inflammation: The presence of StAR in the immune cell called a macrophage has also been shown to induce the creation of 27-hydroxycholesterol. 27-hydroxycholesterol may be effective on its own in preventing the formation of inflammatory factors linked to cardiovascular disease. Though a link between StAR and heart disease is not yet clear.
Myocardial Infarction: StAR expression was detected in cardiac fibroblasts after myocardial infarction. The anti-apoptotic impact of StAR on fibroblasts may enable them to survive the early stress of an infarct, differentiate, and function in tissue repair.
Cholesterol must be transported from the outer mitochondrial membrane to the inner mitochondrial membrane, where the cholesterol side chain is cleaved by the cytochrome P450scc enzyme (CYP11A1), which is the first enzymatic step in all steroid production.
The lipophilic cholesterol cannot traverse the aqueous phase between these two membranes unless particular proteins aid in the process.
Several proteins have been postulated in the past to aid this transfer, including:
sterol carrier protein 2 (SCP2)
steroidogenic activator polypeptide (SAP)
peripheral benzodiazepine receptor (PBR or translocator protein, TSPO)
steroidogenic acute regulatory protein (StAR, or STARD1)
It is now clear that the activity of StAR is the primary mediator in this process.
StAR seems to work from the exterior of the mitochondria, and its entrance inside the mitochondria appears to stop its action, hence the mechanism by which it induces cholesterol transport is unknown. Several theories have been proposed.
Some include StAR acting as a shuttle to transport cholesterol. While StAR may bind cholesterol, the large number of cholesterol molecules transferred by the protein suggests that it must function as a cholesterol channel rather than a shuttle.
Another theory is that it causes cholesterol to be pushed into the inner membrane from the outside membrane (cholesterol desorption). StAR may also facilitate cholesterol import by promoting the establishment of contact areas between the outer and inner mitochondrial membranes.
Another theory proposes that StAR works in tandem with PBR to enhance contact site formation by forcing Cl to exit the mitochondria. However, proof of a StAR-PBR interaction has yet to be discovered.
StAR is a mitochondrial protein that is quickly produced when the cell is stimulated to create steroid hormones.
Hormones such as the following increase its synthesis depending on the cell type.
Luteinising hormone (LH)
Angiotensin converting hormone (ACTH)
StAR is generated at the cellular level in response to the activation of the cAMP second messenger pathway, while other systems may be engaged even if cAMP is not.
It has been discovered in all organs capable of producing steroids, including the adrenal cortex, gonads, brain, and nonhuman placenta. The human placenta is one known exception.
Substances that inhibit StAR action may disturb the endocrine system, causing changes in steroid hormone levels and fertility. Some of those substances are listed below.
DEHP (di(2- ethylhexyl) phthalate, a plasticiser)
DBP (Dibutyl phthalate, a plasticiser)
Permethrin (also known as Nix, a medication and an insecticide)
Cypermethrin (CP, a synthetic pyrethroid used as an insecticide)
DES (Diethylstilbestrol, also known as stilbestrol or stilboestrol, a nonsteroidal estrogen medication)
BPA (Bisphenol A, used for making polycarbonates and epoxy resin)
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This evidence based definition and explanation of StAR (steroidogenic acute regulatory protein) features 19 references, listed below.
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✔ Citations with a tick indicate the information is from a trusted source.
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