Role of STAR and SCP2/SCPx in the Transport of Cholesterol and Other Lipids.

Cholesterol is a lipid molecule essential for several key cellular processes including steroidogenesis. As such, the trafficking and distribution of cholesterol is tightly regulated by various pathways that include vesicular and non-vesicular mechanisms. One non-vesicular mechanism is the binding of cholesterol to cholesterol transport proteins, which facilitate the movement of cholesterol between cellular membranes.

Dynamic Remodeling of Membranes and Their Lipids during Acute Hormone-Induced Steroidogenesis in MA-10 Mouse Leydig Tumor Cells.

Lipids play essential roles in numerous cellular processes, including membrane remodeling, signal transduction, the modulation of hormone activity, and steroidogenesis. We chose steroidogenic MA-10 mouse tumor Leydig cells to investigate subcellular lipid localization during steroidogenesis. Electron microscopy showed that cAMP stimulation increased associations between the plasma membrane (PM) and the endoplasmic reticulum (ER) and between the ER and mitochondria.

Identification of Sec23ip, Part of 14-3-3γ Protein Network, as a Regulator of Acute Steroidogenesis in MA-10 Leydig Cells.

Testosterone production occurs in the Leydig cells of the testes and is essential for virilization, development, reproduction, and quality of life. Although the steroidogenic proteins involved in cholesterol conversion to testosterone (T) are well characterized, the causes of reduced T during fetal, neonatal, and adult life remain uncertain. It is well established that normal cellular function is achieved through fine-tuning of multiple rather than single protein networks.

mutations in rats and a human polymorphism impair the rate of steroid synthesis.

The 18 kDa translocator protein (TSPO) is a ubiquitous conserved outer mitochondrial membrane protein implicated in numerous cell and tissue functions, including steroid hormone biosynthesis, respiration, cell proliferation, and apoptosis. TSPO binds with high affinity to cholesterol and numerous compounds, is expressed at high levels in steroid-synthesizing tissues, and mediates cholesterol import into mitochondria, which is the rate-limiting step in steroid formation. In humans, the rs6971 polymorphism on the gene leads to an amino acid substitution in the fifth transmembrane loop of the protein, which is where the cholesterol-binding domain of TSPO is located, and this polymorphism has been associated with anxiety-related disorders.

Plasma Membrane Origin of the Steroidogenic Pool of Cholesterol Used in Hormone-induced Acute Steroid Formation in Leydig Cells.

Hormone-sensitive acute steroid biosynthesis requires trafficking of cholesterol from intracellular sources to the inner mitochondrial membrane. The precise location of the intracellular cholesterol and its transport mechanism are uncertain. Perfringolysin O, produced by Clostridium perfringens, binds cholesterol.