Daidzein-rich isoflavone aglycones inhibit 17β-hydroxysteroid dehydrogenase 1 and increase estrogen sulfotransferase in endometriosis

Abstract

Objective Endometriosis is an estrogen-dependent disease wherein isoflavones interact with estrogen receptors. Daidzein-rich isoflavone aglycones (DRIAs) have been shown to inhibit cell proliferation and aromatase activity in vitro and in vivo. This study aims to investigate the effects of DRIAs on the enzymes involved in estrogen metabolism in endometriosis.Study design Stromal cells isolated from ovarian endometriomas (OESCs) were cultured with DRIAs. Ovarian endometrioma (OE) specimens were obtained from patients who were treated with or without DRIAs. The gene expressions involved in estrogen metabolism and 17β-hydroxysteroid dehydrogenase (HSD17β) 1 activity were analyzed using RT-PCR and thin layer chromatography, respectively.Results HSD17β1 expression in OE specimens was evaluated using immunohistochemical staining. DRIA treatment significantly suppressed HSD17β1 expression and elevated estrogen sulfotransferase (EST) levels in OESCs; however, no differences were observed in HSD17β2, HSD17β7, HSD17β12, and steroid sulfatase (STS) levels. HSD17β1 enzyme activity was inhibited by DRIAs. Furthermore, immunohistochemical analysis confirmed that HSD17β1 expression was suppressed in the OE specimens of patients undergoing treatment with DRIAs.Conclusions DRIA treatment could suppress abnormal estrogen production via EST stimulation as well as the inhibition of aromatase and HSD17β1 activities, suggesting therapeutic potential in endometriosis that needs to be confirmed by our ongoing clinical trial. ay.

Keywords

• Endometriosis
• estrogen synthesis
• 17β-hydroxysteroid dehydrogenase
• estrogen sulfotransferase
• isoflavones