Regulation of Leydig Cell Cholesterol Metabolism

  • Salman Azhar
  • Eve Reaven
Part of the Contemporary Endocrinology book series (COE)


Steroidogenic tissues have special requirements for cholesterol, which is used as a substrate for tissue specific steroid biosynthesis. Because of this, all steroidogenic tissues, including Leydig cells, have evolved multiple cholesterol delivery pathways and an efficient intracellular cholesterol transport system to ensure constant supply and adequate availability of cholesterol. There are four potential sources, which could contribute to the putative “cholesterol pool” needed for steroidogenesis: (a) de novo synthesized cholesterol, (b) stored cholesteryl esters, (c) exogenous lipoprotein-supplied cholesterol, and (d) plasma membrane-derived cholesterol. Among these, the cholesterol-rich plasma lipoproteins are often the most utilized source of cholesterol for steroid production. Cells acquire lipoprotein-cholesterol both by classic LDL receptor-mediated endocytosis and by selective uptake pathways. In the latter case, lipoprotein cholesteryl ester is selectively internalized without the concomitant uptake and lysosomal degradation of the entire lipoprotein particle. This bulk cholesterol delivery pathway is mediated by a scavenger receptor class B, type-I protein, which is highly expressed and hormonally regulated in steroidogenic cells. In addition to an adequate supply of intracellular cholesterol, steroidogenic cells also require efficient and controlled delivery of cholesterol to outer mitochondrial membranes, and subsequently, to inner mitochondrial membranes for P450scc catalyzed pregnenolone production—the precursor product for all steroids. Although, the exact steps involved in intracellular cholesterol transport to the outer mitochondrial membrane are not yet defined, it appears that vesicular/nonvesicular (through carrier protein) transport processes and interactions between mitochondria, and lipid droplets are probably involved. Two highly studied proteins, peripheral-type benzodiazepine receptor, and steroidogenic acute regulatory protein/steroidogenic acute regulatory protein D1, may function individually, or in concert, to subsequently facilitate the transfer of cholesterol from the outer to inner mitochondrial membranes—the rate-limiting step in steroidogenesis. The present chapter highlights the current understanding of these critical events in Leydig cells; i.e., the acquisiton, intracellular processing, transport, and utilization of cholesterol as the substrate for testosterone production.

Key Words

Cholesterol transport cholesterol transport proteins cholesteryl esters endocytic pathway HDL LDL LDL-receptor lipid droplets selective pathway SR-BI steroidogenesis 


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Copyright information

© Humana Press Inc., Totowa, NJ 2007

Authors and Affiliations

  • Salman Azhar
    • 1
    • 2
  • Eve Reaven
    • 1
  1. 1.Geriatric Research, Educationnn and Clinical Center (GRECC)VA Palo Alto Health Care SystemPalo Alto
  2. 2.Division of Gastroenterology and Hepatology, Department of MedicineStanford University School of MedicineStanford

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