Progestins inhibit estradiol-induced vascular endothelial growth factor and stromal cell–derived factor 1 in human endometrial stromal cells
2011
Okada, Hidetaka | Okamoto, Rika | Tsuzuki, Tomoko | Tsuji, Shoko | Yasuda, Katsuhiko | Kanzaki, Hideharu
OBJECTIVE: To investigate whether 17β-estradiol (E₂) and progestins exert direct effects on vascular endothelial growth factor (VEGF) and stromal cell–derived factor 1 (SDF-1/CXCL12) in human endometrial stromal cells (ESCs) and thereby to clarify the regulatory function of these local angiogenic factors in the endometrium. DESIGN: In vitro experiment. SETTING: Research laboratory at Kansai Medical University. PATIENT(S): Fourteen patients undergoing hysterectomy for benign reasons. INTERVENTION(S): ESCs were cultured with E₂ and/or various clinically relevant progestins (medroxyprogesterone acetate [MPA], norethisterone [NET], levonorgestrel [LNG], dienogest [DNG], and progesterone [P]). MAIN OUTCOME MEASURE(S): The mRNA levels and production of VEGF and SDF-1 were assessed by real-time reverse-transcription polymerase chain reaction and ELISA, respectively. RESULT(S): E₂ significantly induced the mRNA levels and protein production of VEGF and SDF-1 in ESCs. MPA could antagonize the E₂-stimulated effects in a time- and dose-dependent manner, and this effect could be reversed by RU-486 (P receptor antagonist). All of the progestins (MPA, NET, LNG, and DNG; 10⁻⁹ to 10⁻⁷ mol/L) attenuated E₂-induced VEGF and SDF-1 production, whereas P showed these inhibitory effects only when present in a high concentration (10⁻⁷ mol/L). CONCLUSION(S): Progestins have inhibitory effects on E₂-induced VEGF and SDF-1 in ESCs. These results may indicate a potential mechanism for action of the female sex steroids in the human endometrium that can be helpful for various clinical applications.
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