title: Brain-derived neurotrophic factor promotes human granulosa-like tumor cell steroidogenesis and proliferation by activating the FSH receptor-mediated signaling pathway.
abstract: Brain-derived neurotrophic factor (BDNF) and FSH receptor (FSHR) are expressed in ovarian granulosa cells, and play important roles in regulating follicle growth and oocyte maturation. Studies have linked the BDNF-associated signaling pathway to FSHR mRNA expression in the regulation of follicle development, but the mechanisms remain unknown. In the current study, we found that BDNF stimulated the secretion of estradiol and progesterone, and increased the proliferation of KGN cells (human granulosa-like tumor cell line). BDNF treatment also increased phosphorylated and ubiquitinated FSHR, and activated cAMP/PKA/CREB signaling pathway. Moreover, inhibition of BDNF expression by siRNA markedly reduced the estradiol secretion and down-regulated FSHR, aromatase and phosphorylated CREB; meanwhile, FSH treatment partly alleviated the effects of BDNF siRNA on KGN cells. These findings suggested that BDNF modulates graunlosa cell functions and the action probably mediated by FSHR-coupled signaling pathway, to affect aromatase-mediated steroidogenesis. These results provide an alternative target to optimize ovarian granulosa cell function.
authors.affiliation: Center of Reproductive Medicine, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Xie
authors.affiliation: Center of Reproductive Medicine, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Li
authors.affiliation: Center of Reproductive Medicine, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Ji
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Center of Reproductive Medicine, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Ding
authors.affiliation: Center of Reproductive Medicine, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Yidan
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Center of Reproductive Medicine, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Jing
authors.affiliation: Department of Medical Statistics, Jinling Hospital, Nanjing University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Yuxiu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Center of Reproductive Medicine, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Jiangsu, People's Republic of China. yaobing@nju.edu.cn.
authors.forename: Bing
authors.initials: B
authors.lastname: Yao
mesh_terms: D001141:Aromatase / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006107:Granulosa Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D011374:Progesterone / Q000378:metabolism*; D011962:Receptors, FSH / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D054875:Ubiquitination
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C000628168:FSHR protein, human; D011962:Receptors, FSH; D011374:Progesterone; D004958:Estradiol; C579455:BDNF protein, human; D001141:Aromatase