2015/07/27 by Jonathan Wolf Mueller, Lorna C Gilligan, Jan Idkowiak +2 · 4 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Estrogen and related hormone effects #Cholesterol and Lipid Metabolism #Protein Kinase Regulation and GTPase Signaling
paper · pdf · doi:10.1210/er.2015-1036
openalex publication_date 2015/07/27 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/26
Steroid sulfation and desulfation are fundamental pathways vital for a functional vertebrate endocrine system. After biosynthesis, hydrophobic steroids are sulfated to expedite circulatory transit. Target cells express transmembrane organic anion-transporting polypeptides that facilitate cellular uptake of sulfated steroids. Once intracellular, sulfatases hydrolyze these steroid sulfate esters to their unconjugated, and usually active, forms. Because most steroids can be sulfated, including cholesterol, pregnenolone, dehydroepiandrosterone, and estrone, understanding the function, tissue distribution, and regulation of sulfation and desulfation processes provides significant insights into normal endocrine function. Not surprisingly, dysregulation of these pathways is associated with numerous pathologies, including steroid-dependent cancers, polycystic ovary syndrome, and X-linked ichthyosis. Here we provide a comprehensive examination of our current knowledge of endocrinerelated sulfation and desulfation pathways. We describe the interplay between sulfatases and sulfotransferases, showing how their expression and regulation influences steroid action. Furthermore, we address the role that organic anion-transporting polypeptides play in regulating intracellular steroid concentrations and how their expression patterns influence many pathologies, especially cancer. Finally, the recent advances in pharmacologically targeting steroidogenic pathways will be examined. (Endocrine Reviews 36: 526 -563, 2015) I. Introduction A. Steroid analysis II. Steroid Sulfatases A. Molecular overview and functionality B. STS cellular and tissue distribution C. The regulation of STS III. Steroid Sulfotransferases and PAPS Synthases A. Molecular overview and functionality B. Tissue and cellular distribution C. Regulation of sulfotransferases and PAPS synthase activity IV. Cellular Influx and Efflux of Sulfated Steroids A. OATP-regulated influx B. MRP-regulated efflux C. Estrone sulfate influx and efflux D. DHEAS influx and efflux E.