Journalartikel

Jahr der Veröffentlichung: 2018

Seiten: 26-35

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.2017.09.004

Verlag: Elsevier

Abstract: 
Sulfo-conjugated steroid hormones, such as dehydroepiandrosterone sulfate (DHEAS), pregnenolone sulfate or estrone-3-sulfate are abundant in the body, but are biologically inactive at classical androgen and estrogen steroid receptors. However, after carrier-mediated import and de-conjugation by the steroid sulfatase, these compounds participate in the overall steroid regulation of reproductive organs. The sodium-dependent organic anion transporter SOAT, coded by the SLC10A6 gene, is specific for the transport of steroid sulfates and is highly expressed in testicular germ cells, including pachytene spermatocytes, secondary spermatocytes, and round spermatids. Therefore, SOAT is supposed to be involved in the regulation of spermatogenesis and male fertility. In the present study, the SLC10A6 gene was analyzed for rare genetic variants, which might affect transport function or membrane expression of SOAT. Among the 31 SOAT variants analyzed, L44P, Q75R, P107L, G109S, S112F, N113K, S133F, G241D, G263E, G294R, and Y308N showed no transport activity for DHEAS at all. In the case of P107L, G241D, G263E, and Y308N, this was most likely due to significantly reduced expression in the plasma membrane. Other variants are located directly at (Q75R, S112F, N113K) or close to (G109S, S133F, and G263E) the supposed SOAT Na binding sites and thus could disable the sodium-coupled transport cycle. If these loss-of-function SOAT variants are more frequent in men with impaired spermatogenesis or infertility needs further investigation.

Harvard-Zitierstil: Bennien, J., Fischer, T. and Geyer, J. (2018) Rare genetic variants in the sodium-dependent organic anion transporter SOAT (SLC10A6): Effects on transport function and membrane expression, The Journal of Steroid Biochemistry and Molecular Biology, 179, pp. 26-35. https://doi.org/10.1016/j.jsbmb.2017.09.004

APA-Zitierstil: Bennien, J., Fischer, T., & Geyer, J. (2018). Rare genetic variants in the sodium-dependent organic anion transporter SOAT (SLC10A6): Effects on transport function and membrane expression. The Journal of Steroid Biochemistry and Molecular Biology. 179, 26-35. https://doi.org/10.1016/j.jsbmb.2017.09.004