2β- and 16β-hydroxylase activity of CYP11A1 and direct stimulatory effect of estrogens on pregnenolone formation

The Journal of Steroid Biochemistry and Molecular Biology
A MosaRita Bernhardt

Abstract

The biosynthesis of steroid hormones in vertebrates is initiated by the cytochrome P450 CYP11A1, which performs the side-chain cleavage of cholesterol thereby producing pregnenolone. In this study, we report a direct stimulatory effect of the estrogens estradiol and estrone onto the pregnenolone formation in a reconstituted in vitro system consisting of purified CYP11A1 and its natural redox partners. We demonstrated the formation of new products from 11-deoxycorticosterone (DOC), androstenedione, testosterone and dehydroepiandrosterone (DHEA) during the in vitro reaction catalyzed by CYP11A1. In addition, we also established an Escherichia coli-based whole-cell biocatalytic system consisting of CYP11A1 and its redox partners to obtain sufficient yields of products for NMR-characterization. Our results indicate that CYP11A1, in addition to the previously described 6β-hydroxylase activity, possesses a 2β-hydroxylase activity towards DOC and androstenedione as well as a 16β-hydroxylase activity towards DHEA. We also showed that CYP11A1 is able to perform the 6β-hydroxylation of testosterone, a reaction that has been predominantly attributed to CYP3A4. Our results are the first evidence that sex hormones positively regulate the ov...Continue Reading

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Citations

Dec 15, 2015·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Lina SchifferRita Bernhardt
Jun 3, 2016·Expert Opinion on Drug Metabolism & Toxicology·Xiaoman LiuAlan V Boddy
Jan 10, 2017·The Journal of Steroid Biochemistry and Molecular Biology·J NeunzigR Bernhardt
Oct 21, 2015·Chembiochem : a European Journal of Chemical Biology·Yogan KhatriRita Bernhardt
Jan 16, 2020·Animals : an Open Access Journal From MDPI·Adnan KhanYachun Wang
Feb 26, 2020·Journal of Animal Science and Biotechnology·Adnan KhanHuabin Zhu
Mar 17, 2021·Molecular and Cellular Endocrinology·Rita Bernhardt, Jens Neunzig
Jun 7, 2021·The FEBS Journal·Philip HartzRita Bernhardt

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