Effects of 1,25-Dihydroxy Vitamin D3 on Endometriosis

Mariko Miyashita‐Ishiwata, Mariko Miyashita, Kaori Koga, Gentaro Izumi, Fusako Sue, Tomoko Makabe, Ayumi Taguchi, Miwako Nagai, Yoko Urata, Masashi Takamura, Miyuki Harada, Tetsuya Hirata, Yasushi Hirota, Osamu Wada‐Hiraike, Osamu Wada-Hiraike, Tomoyuki Fujii, Yutaka Osuga
The Journal of clinical endocrinology and metabolism · 2016 · vol. 101(6) , pp. 2371–2379 · doi:10.1210/jc.2016-1515 · PMID:27035829 · W2334938013
article OA: bronze CC0 ⤵ 77 in-corpus citations
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1,25-dihydroxy vitamin D3 suppressed inflammation and proliferation in human endometriotic stromal cells, and lower serum vitamin D levels were associated with endometriosis.

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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.

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Condition tags

mesh:D004715endometriosisendometrioma

MeSH descriptors

Calcitriol Endometriosis Endometrium Ovarian Diseases Stromal Cells Vitamin D Adult Apoptosis Apoptosis Calcitriol Cell Proliferation Cell Proliferation Cells, Cultured Cyclooxygenase 2 Cyclooxygenase 2 Cyclooxygenase 2 Endometriosis Endometriosis Endometriosis Endometrium

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