title: FSH-induced p38-MAPK-mediated dephosphorylation at serine 727 of the signal transducer and activator of transcription 1 decreases Cyp1b1 expression in mouse granulosa cells.
abstract: Most mammalian follicles undergo atresia at various stages before ovulation, and granulosa cell apoptosis is a major cause of antral follicular atresia. Estradiol is an essential mitogen for granulosa cell proliferation in vivo and inhibition of apoptosis. The estradiol-producing capacity and metabolism levels are important for follicle health, and sufficient estradiol is necessary for follicle development and ovulation. Cyp1b1, a member of the cytochrome P450 1 subfamily, is responsible for the metabolism of a wide variety of halogenated and polycyclic aromatic hydrocarbons in diverse tissues. In mouse follicles, Cyp1b1 converts estradiol to 4-hydroxyestradiol. We investigated mouse granulosa cells (MGCs) in vivo and in vitro and found that Cyp1b1 played a crucial role in estradiol metabolism in dominant follicles. Follicle-stimulating hormone (FSH) decreased estrogen metabolism by reducing Cyp1b1 mRNA and protein levels in MGCs. Furthermore, FSH regulated signal transducer and activator of transcription 1 (STAT1), a significant transcription factor of Cyp1b1, by mediating the dephosphorylation of STAT1 on serine 727 (Ser(727)) in MGCs. p38 mitogen-activated protein kinase (MAPK) may be involved in the FSH-induced dephosphorylation of STAT1 on Ser(727) in MGCs. These results suggested that FSH functions via p38 MAPK-induced dephosphorylation at Ser(727) of STAT1 to downregulate Cyp1b1 expression and maintain the estradiol levels in mouse dominant follicles.
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.
authors.forename: Xue-Hai
authors.initials: XH
authors.lastname: Du
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Zhou
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Cao
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xiao
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Teng
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.
authors.forename: Cai-Bo
authors.initials: CB
authors.lastname: Ning
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China. Electronic address: liuhonglin@njau.edu.cn.
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Liu
mesh_terms: D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D002393:Estrogens, Catechol / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D008954:Models, Biological; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D002393:Estrogens, Catechol; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; D010768:Phosphoserine; D005640:Follicle Stimulating Hormone; C014036:4-hydroxyestradiol; C585498:Cyp1b1 protein, mouse; D065633:Cytochrome P-450 CYP1B1; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Cyp1b1; FSH; Granulosa cell; STAT1; p38 MAPK