Submitted on March 13, 2003
Revised on April 21, 2003
Accepted on April 21, 2003
Cholesterol sulfate in human physiology: what's it all about?
Charles A. Strott
National Institutes of Health, Bethesda, MD 20892-4510
Corresponding Author: chastro{at}mail.nih.gov
Abstract Cholesterol sulfate is quantitatively the most important known sterol sulfate in human plasma and is present in a concentration that overlaps that of the other abundant circulating steroid sulfate, dehydroepiandrosterone (DHEA) sulfate. Although these sulfolipids have similar production and metabolic clearance rates, they arise from distinct sources and are metabolized by different pathways. While the function of DHEA sulfate remains an enigma, cholesterol sulfate has emerged as an important regulatory molecule. Cholesterol sulfate is a component of cell membranes where it has a stabilizing role, e.g. protecting erythrocytes from osmotic lysis and regulating sperm capacitation. It is present in platelet membranes where it supports platelet adhesion. Cholesterol sulfate can regulate the activity serine proteases, e.g. those involved in blood clotting, fibrinolysis and epidermal cell adhesion. As a result of its ability to regulate the activity of selective protein kinase C isoforms and modulate the specificity of phosphatidylinositol 3-kinase, cholesterol sulfate is involved in signal transduction. Cholesterol sulfate functions in keratinocyte differentiation inducing genes that encode for key components involved in development of the barrier. The accumulating evidence demonstrating a regulatory function for cholesterol sulfate appears solid; the challenge now is to decipher the molecular mechanisms whereby this interesting molecule carries out its various roles.
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