Drospirenone reduces inflammatory cytokines, vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) expression in human endometriotic stromal cells

Makabe T, Tomoko Makabe, Kaori Koga, Miyashita M, Mariko Miyashita‐Ishiwata, Mariko Miyashita, Arisa Takeuchi, Takeuchi A, Sue F, Fusako Sue, Ayumi Taguchi, Taguchi A, Yoko Urata, Urata Y, Izumi G, Gentaro Izumi, Masashi Takamura, Takamura M, Miyuki Harada, Tetsuya Hirata, Yasushi Hirota, Osamu Wada-Hiraike, Osamu Wada‐Hiraike, Tomoyuki Fujii, Fujii T, Osuga Y, Yutaka Osuga
Journal of Reproductive Immunology · 2016 · vol. 119 , pp. 44–48 · doi:10.1016/j.jri.2016.12.002 · PMID:28064076 · W2565310977
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This study investigated the effect of drospirenone on the expression of inflammatory cytokines, VEGF, and NGF in human endometriotic stromal cells.

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Abstract

Drospirenone has been used as a progestin in oral contraceptives with ethinyl estradiol (DRSP/EE) and is expected to regulate endometriosis, however, the direct effects of drospirenone on endometriosis have not been clarified. The aim of this study was to evaluate the anti-inflammatory, anti-angiogenic and anti-neurogenic effects of drospirenone on endometriotic stromal cells (ESC). ESC isolated from endometriotic tissues were obtained from patients during laparoscopic surgery for ovarian endometriosis. ESC were exposed to IL-1β and cultured in the absence or presence of drospirenone. mRNA expression was evaluated using quantitative RT-PCR, and protein was measured using ELISAs. To evaluate the effect of drospirenone on progesterone receptor (PR) and mineralocorticoid receptor (MR), ESC were transfected with siRNA against PR (siPR) and MR (siMR), and cultured in the presence or absence of drospirenone. Drospirenone significantly decreased IL-6, IL-8, VEGF and NGF mRNA expression by ESC. Drospirenone (10-5M) significantly decreased IL-6 secretion and 10-7M drospirenone decreased IL-8 and VEGF secretion. Knockdown of PR, but not MR, negated the effects of drospirenone. In summary, this study demonstrates that drospirenone has anti-inflammatory, anti-angiogenic and anti-neurogenic effects on ESC and these effects are mediated by PR. These drospirenone effects may contribute to the regulatory effects of drospirenone-containing oral contraceptives on endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Androstenes Anti-Inflammatory Agents Endometriosis Endometrium Stromal Cells Adult Androstenes Androstenes Anti-Inflammatory Agents Anti-Inflammatory Agents Cells, Cultured Contraceptives, Oral Contraceptives, Oral Cytokines Cytokines Cytokines Endometriosis Endometrium Ethinyl Estradiol Ethinyl Estradiol

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