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Journal of Lipid Research, Vol. 44, 1268-1278, July 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

Review

Cholesterol sulfate in human physiology

Charles A. Strott¹ and Yuko Higashi

Section on Steroid Regulation, Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-4510

¹ To whom correspondence should be addressed. e-mail: chastro{at}mail.nih.gov

Cholesterol sulfate is quantitatively the most important known sterol sulfate in human plasma, where it 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 of 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 work out the molecular mechanisms whereby this interesting molecule carries out its various roles.

Abbreviations: DHEA, dehydroepiandrosterone; MCR, metabolic clearance rate; P₄₅₀, cytochrome P₄₅₀; PR, production rate; [S], plasma steroid/sterol concentration; SCC, side-chain cleavage; SULT, cytosolic sulfotransferase

Supplementary key words sterol • sulfonation sulfoconjugation • sulfotransferase • signal transduction

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