The Mechanism Of Farnesoid X Receptor(FXR)in Pituitary Adenomas

Pituitary adenoma is one of the most common central nervous system tumors.Pituitary adenomas account for about 10%of brain tumors and the incidence is increasing in recent years.PRL-secreting pituitary adenomas and GH-secreting pituitary adenomas are the main kinds of the pituitary adenoma.Pituitary tumors are harmful to patients,which can cause metabolic and endocrine disorders.In addition,the clinical symptoms of pituitary adenomas are acromegaly and multisystem organ failure.Further pathogenesis researches of pituitary adenomas are urgent for many patients.FXR,as a ligand activated transcription factor,is a nuclear receptor(NR).And FXR can be detected in many organs.Many reports showed that FXR was involved in metabolic regulations such as bile acid,lipid and glucose metabolism.FXR also plays an important role in the regulation of inflammation and cancer.Adenosine 5’-monophosphate(AMP)-activated protein kinase(AMPK)is a heterotrimeric enzyme,which comprise of catalytic α subunit,β subunit,and y subunit.The main function of AMPK is to regulate the energy metabolism of organisms.In addition,reports in recent years mentioned that AMPK played a key role in regulating the development of cancer.In our study,we showed that FXR inhibited the progression of pituitary adenomas through AMPK signal pathway.In this project,the mechanism of FXR in pituitary adenomas was studied through in vitro and in vivo experiments.In vitro experiments,FXR activation by GW4064 inhibited GH3 cell proliferation and had no significant effect on cell migration.Activated FXR induced cell apoptosis and cell cycle arrest in G0/G1 phase.We also found that FXR activation suppressed the expression of CDK2,Cyclin E1,Cyclin D1 and Bcl-2.Furthermore,FXR activation promoted the expression of LKB1,BAX and Caspase-9.In western blot analysis,FXR activation induced the expression of phosphorylated AMPK.In xenograft model studies,FXR activation repressed the growth of xenograft tumor.Moreover,FXR activation suppressed the expression of CDK2,Cyclin E1 and Bcl-2 and promoted the expression of LKB1 and BAX in xenograft.In summary,FXR activation can effectively repress the progression of pituitary adenomas by inducing AMPK signal pathway.Therefore,FXR is a potential target for pituitary adenomas treatment.