Projects per year
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.
Original language | English |
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Pages (from-to) | 526-563 |
Number of pages | 38 |
Journal | Endocrine Reviews |
Volume | 36 |
Issue number | 5 |
Early online date | 27 Jul 2015 |
DOIs | |
Publication status | Published - Oct 2015 |
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Dive into the research topics of 'The Regulation of Steroid Action by Sulfation and Desulfation'. Together they form a unique fingerprint.Projects
- 4 Finished
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The Role of DHEA Sulfation in the Pre-Receptor Regulation of Androgen Excess
Arlt, W. (Principal Investigator)
1/10/11 → 30/09/14
Project: Research
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The role of DHEA sulfation in childhood androgen excess
Idkowiak, J. (Principal Investigator), Arlt, W. (Co-Investigator) & Barrett, T. (Co-Investigator)
1/05/11 → 30/04/13
Project: Research Councils
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Steroid Profiling as a Biomarker Tool in the Diagnosis and Monitoring of Adrenal Tumours
Arlt, W. (Principal Investigator) & Stewart, P. (Co-Investigator)
2/03/09 → 29/02/12
Project: Research Councils
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Pre-Receptor Regulation of Dehydroepiandrosterone Synthesis, Metabolism and Action
Arlt, W. (Principal Investigator)
1/08/04 → 31/10/09
Project: Research Councils