title: The Regulation of Steroid Action by Sulfation and Desulfation.
abstract: 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 endocrine-related 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.
authors.affiliation: Centre for Endocrinology, Diabetes, and Metabolism, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Mueller
authors.affiliation: Centre for Endocrinology, Diabetes, and Metabolism, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Lorna C
authors.initials: LC
authors.lastname: Gilligan
authors.affiliation: Centre for Endocrinology, Diabetes, and Metabolism, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Jan
authors.initials: J
authors.lastname: Idkowiak
authors.affiliation: Centre for Endocrinology, Diabetes, and Metabolism, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Arlt
authors.affiliation: Centre for Endocrinology, Diabetes, and Metabolism, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Foster
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D006801:Humans; D058990:Molecular Targeted Therapy; D009097:Multienzyme Complexes / Q000378:metabolism; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism; D013256:Steroids / Q000378:metabolism*; D043266:Steryl-Sulfatase / Q000378:metabolism*; D013430:Sulfate Adenylyltransferase / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism*
chemical_list: D009097:Multienzyme Complexes; D013256:Steroids; C022322:PAPS synthetase; D013430:Sulfate Adenylyltransferase; D015238:Sulfotransferases; C044251:steroid sulfotransferase; D043266:Steryl-Sulfatase