TY - JOUR
T1 - 1,25-dihydroxyvitamin D3 regulates expression of sex steroid receptors in human uterine fibroid cells
AU - Al-Hendy, Ayman
AU - Diamond, Michael P.
AU - El-Sohemy, Ahmed
AU - Halder, Sunil K.
N1 - Publisher Copyright:
Copyright © 2015 by the Endocrine Society.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - Context: 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. Design: 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. Main Outcome Measures: 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 HuL Mcells. 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.
AB - Context: 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. Design: 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. Main Outcome Measures: 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 HuL Mcells. 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.
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U2 - 10.1210/jc.2014-4011
DO - 10.1210/jc.2014-4011
M3 - Article
C2 - 25625804
AN - SCOPUS:84927611276
SN - 0021-972X
VL - 100
SP - E572-E582
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 4
ER -
