Objective: Estrogen interacts with a membrane receptor, G protein-coupled estrogen receptor (GPER). It was reported that 17β-estradiol was able to inhibit contraction of the human colon and cause relaxation of the guinea pig gallbladder, however, the involvement of GPER was not clarified. The aim of the present study was to investigate the effect of estrogen on human gallbladder motility and the possible role of GPER.
Materials and methods: Relaxation of human gallbladder strips were measured using isometric transducers. Expression of GPER was evaluated by reverse transcription polymerase chain reaction (PCR), realtime PCR, and immunohistochemistry.
Results: In human gallbladder strips, 17β-estradiol and G-1 elicited marked and rapid relaxation, whereas tamoxifen produced mild concentration-dependent relaxation. The relative efficacies to cause relaxation were as follows: 17β-estradiol = G-1 > tamoxifen. The relaxant response of 17β-estradiol was not attenuated by tetrodotoxin or conotoxin GVIA. This implies that nerve stimulation was not involved in the 17β-estradiol-induced gallbladder relaxation. Analysis by reverse transcription PCR and real-time PCR showed that GPER was expressed in the human gallbladder. Further analysis by immunohisto-chemistry revealed that GPER was expressed in the gallbladder muscle. This suggests that 17β-estradiol relaxes the human gallbladder via GPER.
Conclusion: These results demonstrate for the first time that 17β-estradiol and GPER agonist G-1 cause relaxation of the human gallbladder, probably through GPER. Estrogen might play an important role in the control of human gallbladder motility.
Keywords: Estrogen; G protein-coupled estrogen receptor; Gallbladder; Motility.