Human uterine leiomyoma contains low levels of 1, 25 dihdroxyvitamin D3, and shows dysregulated expression of vitamin D metabolizing enzymes

Objectives: To evaluate tissue concentration of 1, 25 dihydroxyvitamin D3, and gene expression level of CYP27B1 that codes for 1-alpha hydroxylase (vitamin D activating enzyme), and CYP24A1 that codes for 24-hydroxylase (vitamin D catabolizing enzyme) in human uterine leiomyoma (ULM), its adjacent myometrium (Myo-F), and normal myometrium (Myo-N). Study design: Levels of 1, 25 dihydroxyvitamin D3 were measured using HPLC and Diode detectors whereas CYP27B1, and CYP24A1 expressions were assessed using Real-Time PCR in ULM, Myo-F, and Myo-N. Non-parametric statistics were used. Results: ULM5 contained significantly less 1, 25 dihydroxy vitamin D3 compared to Myo-F (3.0, IQR: 1.0-9.0 versus 6.0, IQR: 3.0-13.0 mu g/kg, P value is 0.03). No significant difference was detected between ULM and Myo-N, or Myo-F and Myo-N. Intratumoral level of the active form of vitamin D did not differ according to the type of ULM (submucous or interstitial/subserous), or to the ULM volume. CYP27B1 was expressed in ULM (2.17, IQR: 0.65-4.9), Myo-F (4.94, IQR: 1.04-22.59), and Myo-N (0.99, IQR: 0.49-1.71) to a comparable level. CYP24A1 expression was significantly higher in ULM compared to Myo-N (2,00, IQR: 0.69-10.77 versus 0.22, IQR: 00- 0.96, respectively, P value is 0.04). Conclusions: Human ULM5 contain significantly lower 1, 25 dihydroxyvitamin D3 than its adjacent myometrium. ULM, Myo-F, and Myo-N express CYP27B1 and CYP24A1. ULMs express significantly higher level of CYP24A1 than normal myometrium indicating that over expression of 24-hydroxylase is a mechanism by which ULMs sustain a relative state of hypovitaminosis D. (C) 2018 Elsevier B.V. All rights reserved.