2. Academic Validation
  3. Transport of steroid 3-sulfates and steroid 17-sulfates by the sodium-dependent organic anion transporter SOAT (SLC10A6)

Transport of steroid 3-sulfates and steroid 17-sulfates by the sodium-dependent organic anion transporter SOAT (SLC10A6)

  • J Steroid Biochem Mol Biol. 2018 May;179:20-25. doi: 10.1016/j.jsbmb.2017.09.013.
Gary Grosser 1,  Josefine Bennien 1,  Alberto Sánchez-Guijo 2,  Katharina Bakhaus 1,  Barbara Döring 1,  Michaela Hartmann 2,  Stefan A Wudy 2,  Joachim Geyer 3
Affiliations

Affiliations

  • 1 Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus Liebig University Giessen, Germany.
  • 2 Steroid Research and Mass Spectrometry Unit, Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University Giessen, Germany.
  • 3 Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus Liebig University Giessen, Germany. Electronic address: [email protected].
PMID: 28951227 DOI: 10.1016/j.jsbmb.2017.09.013
Abstract

The sodium-dependent organic anion transporter SOAT/Soat shows highly specific transport activity for sulfated Steroids. SOAT substrates identified so far include dehydroepiandrosterone sulfate, 16α-hydroxydehydroepiandrosterone sulfate, estrone-3-sulfate, pregnenolone sulfate, 17β-estradiol-3-sulfate, and androstenediol sulfate. Apart from these compounds, many other sulfated Steroids occur in mammals. Therefore, we aimed to expand the substrate spectrum of SOAT and analyzed the SOAT-mediated transport of eight different sulfated Steroids by combining in vitro transport experiments in SOAT-transfected HEK293 cells with LC-MS/MS analytics of cell lysates. In addition, we aimed to better understand the structural requirements for SOAT substrates and so selected structural pairs varying only at specific positions: 3α/3β-sulfate, 17α/17β-sulfate, mono-sulfate/di-sulfate, and 17α-hydroxylation. We found significant and sodium-dependent SOAT-mediated transport of 17α-hydroxypregnenolone sulfate, 17β-estradiol-17-sulfate, androsterone sulfate, epiandrosterone sulfate, testosterone sulfate, epitestosterone sulfate, and 5α-dihydrotestosterone sulfate. However, 17β-estradiol-3,17-disulfate was not transported by SOAT.

In conclusion: SOAT substrates from the group of sulfated Steroids are characterized by a planar and lipophilic steroid backbone in trans-trans-trans conformation of the rings and a negatively charged mono-sulfate group at positions 3' or 17' with flexibility for α- or β- orientation. Furthermore, 5α-reduction, 16α-hydroxylation, and 17α-hydroxylation are acceptable for SOAT substrate recognition, whereas addition of a second negatively charged sulfate group seems to abolish substrate binding to SOAT, and so 17β-estradiol-3,17-disulfate is not transported by SOAT.

Keywords

17β-Estradiol-17-sulfate; 17β-Estradiol-3,17-disulfate; Epiandrosterone sulfate; SLC10A6; SOAT; Sulfated steroids; Transport.

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