title: 1,25-dihydroxyvitamin D3 regulates expression of sex steroid receptors in human uterine fibroid cells.
abstract: BACKGROUND
  Uterine fibroids (UFs) are the most common benign tumors in premenopausal women. In this study, we evaluated the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] for the treatment of UFs.
  
  
  OBJECTIVE
  To determine the role of 1,25(OH)2D3 on the expression of sex steroid receptors in human UF cells.
  
  
  METHODS
  Human UFs and their adjacent myometrium were analyzed for expression of estrogen receptor (ER)-α, progesterone receptor (PR)-A, and PR-B, as well as members of the steroid receptor coactivator (SRC) family. Immortalized human uterine fibroid (human uterine leiomyoma [HuLM]) cells were treated with 1,25(OH)2D3 and assayed for the expression and localization of the aforementioned receptors and SRCs using Western blot, immunohistochemistry, immunofluorescence, and immunoprecipitation assays.
  
  
  METHODS
  We discovered a correlation between reduced levels of vitamin D receptor (VDR) and increased levels of ER-α, PR-A, and PR-B in these tissues. We evaluated the effects of 1,25(OH)2D3 on the regulation of the aforementioned sex steroid receptors.
  
  
  RESULTS
  We observed an inverse correlation between the up-regulated ER-α, PR-A, and PR-B and expression of VDR in UFs. Treatment with 1,25(OH)2D3 significantly decreased levels of ER-α, PR-A, and PR-B, as well as SRCs in HuLM cells (P < .05). In contrast, 1,25(OH)2D3 self-induced its own VDR, which resulted in an induction of VDR-retinoid X receptor-α complex in HuLM cells. Together, these results suggest that 1,25(OH)2D3 functions as an antagonist of sex steroid hormone receptors in HuLM cells.
  
  
  CONCLUSIONS
  1,25(OH)2D3 functions as a potent antiestrogenic/antiprogesteronic agent that may have utility as a novel therapeutic option for UF.
authors.affiliation: Department of Obstetrics and Gynecology (A.A.-H., M.P.D., S.K.H.), Georgia Regents University, Medical College of Georgia, Augusta, Georgia 30912; and Department of Nutritional Sciences (A.E.-S.), University of Toronto, Toronto, Canada M5S 3E2.
authors.forename: Ayman
authors.initials: A
authors.lastname: Al-Hendy
authors.forename: Michael P
authors.initials: MP
authors.lastname: Diamond
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Sohemy
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Halder
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000378:metabolism* / Q000473:pathology; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018167:Receptors, Calcitriol / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D018167:Receptors, Calcitriol; D011980:Receptors, Progesterone; C118756:dihydroxy-vitamin D3; D014807:Vitamin D