The PD‐1/PD‐L1 binding inhibitor BMS‐202 suppresses the synthesis and secretion of gonadotropins and enhances apoptosis via p38 MAPK signaling pathway. Issue 1 (26th July 2021)

• Record Type: Journal Article
• Authors: Jiang, Ying; Zhang, Jinglin; Qiu, Jingtao; Cui, Sheng
• Is Part Of: Drug development research. Volume 83:Issue 1(2022)
• Page Start: 176
• Page End: 183
• Publication Date: 2021-07-26
• Subjects: apoptosis -- BMS‐202 -- estrous cycle -- gonadotropin -- p38 MAPK; Drug development -- Periodicals; Drugs -- Research -- Periodicals; 615.19
• DOI: 10.1002/ddr.21857
• Languages: English
• ISSNs: 0272-4391

Abstract

Abstract: To determine whether BMS‐202 can disrupt the pituitary gland and reproductive system. BMS‐202 (2.5 mg/kg) was injected intraperitoneally into adult female mice every 96 h for four times. Real‐time polymerase chain reaction, western blotting, double immunofluorescence staining and radioimmunoassays (RIA) were used to study the expressions of programmed death receptor 1 (PD‐1) and programmed death ligand 1 (PD‐L1), and detect changes after BMS‐202 treatment in the mouse pituitary gland. PD‐1 and PD‐L1 were expressed in the mouse pituitary gland. Further functional studies demonstrated that BMS‐202 inhibited the synthesis and secretion of gonadotropins and prolonged the estrous cycle in mice. Moreover, the increases of cleaved caspase3 (c‐caspase3) protein level both in vivo and in vitro indicated that BMS‐202 induced apoptosis. Additionally, the effects of BMS‐202 on follicle‐stimulating hormone and luteinizing hormone mRNA levels were blocked by a p38 MAPK inhibitor. Of note, the inhibition of p38 MAPK pathway decreased the apoptosis induced by BMS‐202. BMS‐202, as a drug which inhibits the formation of the PD‐1/PD‐L1 complex, disrupts the normal function of the pituitary gland. Importantly, the results confirmed the potential insecurity of BMS‐202 in the pituitary gland and provided data to support the evaluation of its clinical application.