The regulation of steroid action by sulfation and desulfation
File(s)
Published version
Author(s)
Mueller, Jonathan W
Gilligan, Lorna C
Idkowiak, Jan
Arlt, Wiebke
Foster, Paul A
Type
Journal Article
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.
Date Issued
2015-10-01
Date Acceptance
2015-07-21
Citation
Endocrine Reviews, 2015, 36 (5), pp.526-563
ISSN
0163-769X
Publisher
Oxford University Press
Start Page
526
End Page
563
Journal / Book Title
Endocrine Reviews
Volume
36
Issue
5
Copyright Statement
© 2015 by the Endocrine Society This article has been published under the terms of the Creative Commons Attribution License (CC-BY; http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright for this article is retained by the author(s).
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/26213785
Subjects
3'-PHOSPHOADENOSINE 5'-PHOSPHOSULFATE PAPS
ANDROGEN-DEPRIVATION THERAPY
CONSTITUTIVE ANDROSTANE RECEPTOR
DEPENDENT BREAST-CANCER
Endocrinology & Metabolism
FORMYLGLYCINE-GENERATING ENZYME
HUMAN DEHYDROEPIANDROSTERONE SULFOTRANSFERASE
HUMAN HYDROXYSTEROID SULFOTRANSFERASE
Life Sciences & Biomedicine
ORGANIC ANION TRANSPORTER
POLYPEPTIDE OATP-B
Science & Technology
X-LINKED ICHTHYOSIS
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2015-10-01