Journal article
Authors list: Neunzig, J; Sánchez-Guijo, A; Mosa, A; Hartmann, MF; Geyer, J; Wudy, SA; Bernhardt, R
Publication year: 2014
Pages: 324-333
Journal: The Journal of Steroid Biochemistry and Molecular Biology
Volume number: 144B
ISSN: 0960-0760
DOI Link: https://doi.org/10.1016/j.jsbmb.2014.07.005
Publisher: Elsevier
Abstract:
In many tissues sulfonated steroids exceed the concentration of free steroids and recently they were also shown to fulfill important physiological functions. While it was previously demonstrated that cholesterol sulfate (CS) is converted by CYP11A1 to pregnenolone sulfate (PregS), further conversion of PregS has not been studied in detail. To investigate whether a steroidogenic pathway for sulfonated steroids exists similar to the one described for free steroids, we examined the interaction of PregS with CYP17A1 in a reconstituted in-vitro system. Difference spectroscopy revealed a K-d-value of 74.8 +/- 4.2 mu M for the CYP17A1-PregS complex, which is 2.5-fold higher compared to the CYP17A1-pregnenolone (Preg) complex. Mass spectrometry experiments proved for the first time that PregS is hydroxylated by CYP17A1 at position C17, identically to pregnenolone. A higher K-m- and a lower k(cat)-value for CYP17A1 using PregS compared with Preg were observed, indicating a 40% reduced catalytic efficiency when using the sulfonated steroid. Furthermore, we analyzed whether the presence of cytochrome b(5) (b(5)) has an influence on the CYP17A1 dependent conversion of PregS, as was demonstrated for Preg. Interestingly, with 17OH-PregS no scission of the 17,20-carbon-carbon bond occurs, when b(5) is added to the reconstituted in-vitro system, while b(5) promotes the formation of DHEA from 17OH-Preg. When using human SOAT-HEK293 cells expressing CYP17A1 and CPR, we could confirm that PregS is metabolized to 17OH-PregS, strengthening the potential physiological meaning of a pathway for sulfonated steroids. (C) 2014 Elsevier Ltd. All rights reserved.
Citation Styles
Harvard Citation style: Neunzig, J., Sánchez-Guijo, A., Mosa, A., Hartmann, M., Geyer, J., Wudy, S., et al. (2014) A steroidogenic pathway for sulfonated steroids: The metabolism of pregnenolone sulfate, The Journal of Steroid Biochemistry and Molecular Biology, 144B, pp. 324-333. https://doi.org/10.1016/j.jsbmb.2014.07.005
APA Citation style: Neunzig, J., Sánchez-Guijo, A., Mosa, A., Hartmann, M., Geyer, J., Wudy, S., & Bernhardt, R. (2014). A steroidogenic pathway for sulfonated steroids: The metabolism of pregnenolone sulfate. The Journal of Steroid Biochemistry and Molecular Biology. 144B, 324-333. https://doi.org/10.1016/j.jsbmb.2014.07.005