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

作者：Makabe Tomoko; Koga Kaori; Miyashita Mariko; Takeuchi Arisa; Sue Fusako; Taguchi Ayumi; Urata Yoko; Izumi Gentaro; Takamura Masashi; Harada Miyuki; Hirata Tetsuya; Hirota Yasushi; Wada Hiraike Osamu; Fujii Tomoyuki; Osuga Yutaka

来源：Journal of Reproductive Immunology, 2017, 119: 44-48.

DOI：10.1016/j.jri.2016.12.002

• Drospirenone
• Endometriosis
• Inflammatory cytokines
• Oral contraceptives

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-1 beta 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(-5) M) significantly decreased IL-6 secretion and 10(-7) M 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.

• 出版日期2017-2