Effects of 1,25-Dihydroxy Vitamin D3 on Endometriosis

J Clin Endocrinol Metab. 2016 Jun;101(6):2371-9. doi: 10.1210/jc.2016-1515. Epub 2016 Apr 1.

Abstract

Context: Endometriosis is an estrogen-dependent, chronic inflammatory disease. Recent studies have shown that vitamin D (VD) is an effective modulator of the immune system and plays an important role in controlling many inflammatory diseases.

Objective: The objective of the study was to clarify the in vitro effects of 1,25-dihydroxy vitamin D3 (1,25[OH]2D3) on human endometriotic stromal cells (ESCs) and to determine the serum levels of VD in endometriosis patients.

Design, patients, and main outcome measures: ESCs were isolated from ovarian endometrioma and cultured with 1,25(OH)2D3. Gene expression of IL-8, cyclooxygenase-2, microsomal prostaglandin E synthase-1, microsomal prostaglandin E synthase-2, cytosolic prostaglandin E synthase, 15-hydroxyprostaglandin dehydrogenase, matrix metalloproteinase (MMP)-2, and MMP-9 was examined using quantitative RT-PCR. The production of IL-8 and prostaglandin E2 was measured using an ELISA and an enzyme immunoassay. Viable cell number was assessed using a cell-counting assay, and DNA synthesis was assessed using the bromodeoxyuridine incorporation assay. Apoptosis was assessed using flow cytometry. The expression of inhibitory-κBα protein was detected using Western blotting. The serum levels of 25-hydroxyvitamin D3 and 1,25(OH)2D3 were measured by a RIA.

Results: In vitro studies showed that 1,25(OH)2D3 significantly reduced IL-1β- or TNF-α-induced inflammatory responses, such as IL-8 expression and prostaglandin activity. 1,25(OH)2D3 also reduced viable ESC numbers and DNA synthesis but did not affect apoptosis. MMP-2 and MMP-9 expressions were reduced by 1,25(OH)2D3. 1,25(OH)2D3 inhibited nuclear factor-κB activation. The serum 25-hydroxyvitamin D3 levels were significantly lower in women with severe endometriosis than in the controls and women with mild endometriosis. Serum 1,25(OH)2D3 levels were not different between groups.

Conclusions: VD modulates inflammation and proliferation in endometriotic cells, and a lower VD status is associated with endometriosis. Taken together, VD supplementation could be a novel therapeutic strategy for managing endometriosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis / drug effects
  • Calcitriol / pharmacology*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Endometriosis / blood*
  • Endometriosis / metabolism
  • Endometriosis / pathology
  • Endometrium / drug effects*
  • Endometrium / metabolism
  • Endometrium / pathology
  • Female
  • Gene Expression / drug effects
  • Humans
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Ovarian Diseases / blood*
  • Ovarian Diseases / metabolism
  • Ovarian Diseases / pathology
  • Prostaglandin-E Synthases / genetics
  • Prostaglandin-E Synthases / metabolism
  • Stromal Cells / drug effects*
  • Stromal Cells / metabolism
  • Stromal Cells / pathology
  • Vitamin D / blood*

Substances

  • Interleukin-8
  • Vitamin D
  • Cyclooxygenase 2
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • PTGES protein, human
  • Prostaglandin-E Synthases
  • Calcitriol