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BMS\u2010202 (2.5\u00a0mg\/kg) was injected intraperitoneally into adult female mice every 96\u2009h for four times. Real\u2010time polymerase chain reaction, western blotting, double immunofluorescence staining and radioimmunoassays (RIA) were used to study the expressions of programmed death receptor 1 (PD\u20101) and programmed death ligand 1 (PD\u2010L1), and detect changes after BMS\u2010202 treatment in the mouse pituitary gland. PD\u20101 and PD\u2010L1 were expressed in the mouse pituitary gland. Further functional studies demonstrated that BMS\u2010202 inhibited the synthesis and secretion of gonadotropins and prolonged the estrous cycle in mice. Moreover, the increases of cleaved caspase3 (c\u2010caspase3) protein level both in vivo and in vitro indicated that BMS\u2010202 induced apoptosis. Additionally, the effects of BMS\u2010202 on follicle\u2010stimulating 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\u2010202. BMS\u2010202, as a drug which inhibits the formation of the PD\u20101\/PD\u2010L1 complex, disrupts the normal function of the pituitary gland. Importantly, the results confirmed the potential insecurity of BMS\u2010202 in the pituitary gland and provided data to support the evaluation of its clinical application.<\/jats:p>","DOI":"10.1002\/ddr.21857","type":"journal-article","created":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T07:37:40Z","timestamp":1627285060000},"page":"176-183","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The <scp>PD<\/scp>\u20101<b>\/<\/b><scp>PD\u2010L1<\/scp> binding inhibitor <scp>BMS<\/scp>\u2010202 suppresses the synthesis and secretion of gonadotropins and enhances apoptosis via p38 <scp>MAPK<\/scp> signaling pathway"],"prefix":"10.1002","volume":"83","author":[{"given":"Ying","family":"Jiang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Agrobiotechnology College of Biological Sciences, China Agricultural University  Beijing 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