Studies on CYP3A activity during the menstrual cycle as measured by urinary 6β-hydroxycortisol/cortisol.

Autor: Bergström H; Department of Neurobiology, Care Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Huddinge, Sweden., Lindahl A; Department of Laboratory Medicine, Division of Clinical Chemistry, Karolinska Institutet, Stockholm, Sweden.; Department of Clinical Chemistry, Karolinska University Laboratory, Karolinska University Hospital, Stockholm, Sweden., Warnqvist A; Department of Environmental Medicine, Division of Biostatistics, Karolinska Institutet, Stockholm, Sweden., Diczfalusy U; Department of Laboratory Medicine, Division of Clinical Chemistry, Karolinska Institutet, Stockholm, Sweden.; Department of Clinical Chemistry, Karolinska University Laboratory, Karolinska University Hospital, Stockholm, Sweden., Ekström L; Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Björkhem-Bergman L; Department of Neurobiology, Care Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Huddinge, Sweden.; Department of Palliative Medicine, Stockholms Sjukhem, Stockholm, Sweden.
Jazyk: angličtina
Zdroj: Pharmacology research & perspectives [Pharmacol Res Perspect] 2021 Dec; Vol. 9 (6), pp. e00884.
DOI: 10.1002/prp2.884
Abstrakt: The 6β-OH-cortisol/cortisol ratio (6β-OHC/C) in urine is an endogenous marker of drug-metabolizing enzyme cytochrome P450 3A (CYP3A). The primary aim of this single center, prospective, non-interventional cohort study, was to investigate the variability of 6β-OHC/C during the menstrual cycle. In addition, possible associations between the CYP3A activity and sex hormones, gut microbiota metabolite trimethylamine-N-Oxide (TMAO) and microRNA-27b, respectively, were investigated. Serum and urinary samples from healthy, regularly menstruating women followed for two menstrual cycles were analyzed. Twenty-six complete menstrual cycles including follicular, ovulatory, and luteal phase were defined based on hormone analyses in serum. 6β-OHC/C were analyzed in urine and sex hormones, TMAO and miRNA-27b were analyzed in serum at the same time points. 6β-OHC/C did not vary between the follicular, ovulatory, or luteal phases. There was a difference in the relative miRNA-27b expression between the follicular and ovulatory phase (p = .03). A significant association was found between 6β-OHC/C and progesterone during the follicular (p = .005) and ovulatory (p = .01) phases (n = 26 for each phase). In addition, a significant association was found between the ratio and TMAO during the ovulatory (p = .02) and luteal (p = .002) phases. 6β-OHC/C and gut microbiota TMAO were significantly associated (p = .003) when evaluating all values, for all phases (n = 78). Interestingly, the finding of an association between 6β-OHC/C in urine and levels of TMAO in serum suggest that gut microbiota may affect CYP3A activity.
(© 2021 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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