The mechanisms of estrogen-mediated GPER/YAP pathway in benign hyperplastic prostate.

Benign prostatic hyperplasia (BPH) is a common age-related condition characterized by prostate enlargement, which is influenced by hormonal imbalances and altered signaling pathways. In this study, we investigated the effects of different doses of treatment on prostate tissue in a rat model of BPH, focusing on the G protein‑coupled estrogen receptor (GPER), the downstream signaling molecule Yes-associated protein (YAP), and its phosphorylated form (p-YAP). We measured hormone levels, protein expression, and histopathological changes to evaluate the impact of treatment on prostate growth. Serum estrogen and testosterone levels were assessed using enzyme‑linked immunosorbent assay (ELISA), while GPER, YAP, and p-YAP protein expression were analyzed by Western blot (WB). Immunofluorescence assays for Ki-67 and Caspase-3 were also performed. Our results showed that 17β-estradiol (E2) 50 μg/kg and E2 100 μg/kg treatment significantly increased GPER and p-YAP protein expression, with corresponding increases in prostate tissue proliferation and reduced apoptosis, as indicated by Ki-67 and Caspase-3 expression. In contrast, the inhibitor treatment significantly decreased GPER and p-YAP expression, promoting apoptosis and reducing prostate enlargement. Hormonal assays revealed that estrogen levels were elevated and testosterone levels were reduced in the E2 50 μg/kg and E2 100 μg/kg groups, whereas inhibitor treatment partially reversed these changes in circulating and intraprostatic sex hormone levels. These findings suggest that the GPER/YAP signaling pathway plays a key role in BPH progression and that targeting this pathway may offer a novel therapeutic approach for managing BPH.