Department of Neurobiology, Care Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Huddinge, Sweden.
Department of Laboratory Medicine, Division of Clinical Chemistry, Karolinska Institutet, Stockholm, Sweden.
Pharmacol Res Perspect. 2021 Dec;9(6):e00884. doi: 10.1002/prp2.884.
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.
尿中 6β-OH-皮质醇/皮质醇比值（6β-OHC/C）是细胞色素 P450 3A（CYP3A）代谢酶的内源性标志物。本单中心、前瞻性、非干预性队列研究的主要目的是研究月经周期中 6β-OHC/C 的变异性。此外，还分别研究了 CYP3A 活性与性激素、肠道微生物代谢产物三甲胺 N-氧化物（TMAO）和 microRNA-27b 之间的可能关联。分析了健康、规律月经的女性在两个月经周期内的血清和尿液样本。根据血清中激素分析，定义了 26 个完整的月经周期，包括卵泡期、排卵期和黄体期。在同一时间点分析尿液中的 6β-OHC/C 以及血清中的性激素、TMAO 和 microRNA-27b。6β-OHC/C 在卵泡期、排卵期或黄体期之间没有差异。卵泡期和排卵期之间的相对 microRNA-27b 表达存在差异（p =.03）。在卵泡期（p =.005）和排卵期（p =.01），发现 6β-OHC/C 与孕激素之间存在显著相关性（n = 26）。此外，在排卵期（p =.02）和黄体期（p =.002），发现该比值与 TMAO 之间存在显著相关性。当评估所有阶段（n = 78）的所有值时，6β-OHC/C 和肠道微生物 TMAO 之间存在显著相关性（p =.003）。有趣的是，尿液中 6β-OHC/C 与血清中 TMAO 水平之间的关联表明，肠道微生物可能会影响 CYP3A 活性。
