1,25-dihydroxyvitamin D3 regulates expression of sex steroid receptors in human uterine fibroid cells

Ayman Al-Hendy, Michael Peter Diamond, Ahmed El-Sohemy, Sunil Krishna Halder

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)E572-E582
JournalJournal of Clinical Endocrinology and Metabolism
Volume100
Issue number4
DOIs
StatePublished - Jan 1 2015

Fingerprint

Calcitriol Receptors
Calcitriol
Steroid Receptors
Leiomyoma
Estrogen Receptors
Retinoid X Receptors
Gonadal Steroid Hormones
Tumors
Assays
Tissue
progesterone receptor A
progesterone receptor B
Vitamin B Complex
Myometrium
Immunoprecipitation
Fluorescent Antibody Technique
Therapeutics
Western Blotting
Immunohistochemistry
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

1,25-dihydroxyvitamin D3 regulates expression of sex steroid receptors in human uterine fibroid cells. / Al-Hendy, Ayman; Diamond, Michael Peter; El-Sohemy, Ahmed; Halder, Sunil Krishna.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 100, No. 4, 01.01.2015, p. E572-E582.

Research output: Contribution to journalArticle

@article{35d9c4c9848b45eba6765fa1d08dc68d,
title = "1,25-dihydroxyvitamin D3 regulates expression of sex steroid receptors in human uterine fibroid cells",
abstract = "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.",
author = "Ayman Al-Hendy and Diamond, {Michael Peter} and Ahmed El-Sohemy and Halder, {Sunil Krishna}",
year = "2015",
month = "1",
day = "1",
doi = "10.1210/jc.2014-4011",
language = "English (US)",
volume = "100",
pages = "E572--E582",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "4",

}

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 Peter

AU - El-Sohemy, Ahmed

AU - Halder, Sunil Krishna

PY - 2015/1/1

Y1 - 2015/1/1

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.

UR - http://www.scopus.com/inward/record.url?scp=84927611276&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84927611276&partnerID=8YFLogxK

U2 - 10.1210/jc.2014-4011

DO - 10.1210/jc.2014-4011

M3 - Article

VL - 100

SP - E572-E582

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 4

ER -