Journalartikel

Jahr der Veröffentlichung: 2018

Seiten: 20-25

Zeitschrift: The Journal of Steroid Biochemistry and Molecular Biology

Bandnummer: 179

ISSN: 0960-0760

eISSN: 1879-1220

DOI Link: https://doi.org/10.1016/j.jsbmb.2017.09.013

Verlag: Elsevier

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, 16 alpha-hydroxydehydroepiandrosterone sulfate, estrone-3-sulfate, pregnenolone sulfate, 17 beta-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: 3 alpha/3 beta-sulfate, 17 alpha/17 beta-sulfate, mono-sulfate/di-sulfate, and 17 alpha-hydroxylation. We found significant and sodium-dependent SOAT-mediated transport of 17 alpha-hydroxypregnenolone sulfate, 17 beta-estradiol-17-sulfate, androsterone sulfate, epiandrosterone sulfate, testosterone sulfate, epitestosterone sulfate, and 5 alpha-dihydrotestosterone sulfate. However, 17 beta-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 alpha- or beta- orientation. Furthermore, 5 alpha-reduction, 16 alpha-hydroxylation, and 17 alpha-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 17 beta-estradiol-3,17-disulfate is not transported by SOAT.

Harvard-Zitierstil: Grosser, G., Bennien, J., Sánchez-Guijo, A., Bakhaus, K., Döring, B., Hartmann, M., et al. (2018) Transport of steroid 3-sulfates and steroid 17-sulfates by the sodium-dependent organic anion transporter SOAT (SLC10A6), The Journal of Steroid Biochemistry and Molecular Biology, 179, pp. 20-25. https://doi.org/10.1016/j.jsbmb.2017.09.013

APA-Zitierstil: Grosser, G., Bennien, J., Sánchez-Guijo, A., Bakhaus, K., Döring, B., Hartmann, M., Wudy, S., & Geyer, J. (2018). Transport of steroid 3-sulfates and steroid 17-sulfates by the sodium-dependent organic anion transporter SOAT (SLC10A6). The Journal of Steroid Biochemistry and Molecular Biology. 179, 20-25. https://doi.org/10.1016/j.jsbmb.2017.09.013