title: Citrinin reduces testosterone secretion by inducing apoptosis in rat Leydig cells.
abstract: A previous study has shown that CTN (Citrinin) inhibits mouse testosterone production. In this study, the mechanism by which testosterone production is inhibited by CTN in rat Leydig cells was investigated, and the morphological evidence of apoptosis, including nuclei fragmentation and phosphatidylserine (PS) exposure on cell surfaces, was clearly observed 36h after CTN exposure. The results showed that citrinin at 50 and 100μM significantly suppressed testosterone secretion by human chorionic gonadotropin (hCG) at 10IU/ml. Western blotting results showed that CTN induced formation of processed p53, caspase-9, and caspase-3 proteins in a dose-dependent manner; CTN also induced a dose-dependent increase in caspase-3 catalytic activity. Western blot assays also showed that CTN decreased expression of three key enzymes (P450scc, 3β-HSD-1, and StAR) of testosterone production. Taken together, these results suggested that CTN reduced testosterone secretion by inducing apoptosis in rat Leydig cells, a mechanism that might account for CTN stimulation of p53 expression followed by activation of multiple caspases.
authors.affiliation: College of Biological Science and Technology, Beijing Forestry University, Beijing 100083, People's Republic of China.
authors.forename: Shuqiang
authors.initials: S
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Junwen
authors.initials: J
authors.lastname: Zhang
authors.forename: Dongzhi
authors.initials: D
authors.lastname: Zhang
authors.forename: Meng
authors.initials: M
authors.lastname: Gong
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Wei
authors.forename: Wenhua
authors.initials: W
authors.lastname: Liu
authors.forename: Yongqi
authors.initials: Y
authors.lastname: Wang
authors.forename: Chongxue
authors.initials: C
authors.lastname: Zhao
authors.forename: Yaxiong
authors.initials: Y
authors.lastname: Cui
authors.forename: Defu
authors.initials: D
authors.lastname: Hu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002478:Cells, Cultured; D002953:Citrinin / Q000633:toxicity*; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; D002953:Citrinin; D013739:Testosterone; D053148:Caspase 3; D053453:Caspase 9