title: TGF-β1 downregulates StAR expression and decreases progesterone production through Smad3 and ERK1/2 signaling pathways in human granulosa cells.
abstract: BACKGROUND
  Regulation of progesterone production in granulosa cells is important for normal reproductive functions. Steroidogenic acute regulatory protein (StAR) is recognized as the key regulatory protein involved in the rate-limiting step of steroidogenesis. TGF-β1 protein is detected in human follicular fluid, and TGF-β1 and its receptors are expressed in human granulosa cells. However, the functional role of TGF-β1 in the regulation of StAR expression and progesterone production in human granulosa cells remains unknown.
  
  
  OBJECTIVE
  Our objective was to investigate the effects of TGF-β1 on StAR expression and progesterone production in human granulosa cells.
  
  
  METHODS
  SVOG cells are human granulosa cells that were obtained from women undergoing in vitro fertilization and immortalized with SV40 large T antigen. SVOG cells were used to investigate the effects of TGF-β1 on StAR expression and progesterone production at an academic research center.
  
  
  METHODS
  Levels of mRNA and protein were examined by RT-qPCR and western blotting, respectively. The accumulation levels of progesterone were measured by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  TGF-β1 treatment downregulated StAR expression and decreased progesterone production. The suppressive effects of TGF-β1 on StAR expression and progesterone production were abolished by the inhibition of TGF-β type I receptor. In addition, treatment with TGF-β1 activated the Smad2/3 and ERK1/2 signaling pathways. The inhibition of the Smad3 and ERK1/2 signaling pathways attenuated the TGF-β1-induced downregulation of StAR expression and progesterone production.
  
  
  CONCLUSIONS
  TGF-β1 downregulated StAR expression and decreased progesterone production by activating the Smad3 and ERK1/2 signaling pathways in human granulosa cells.
authors.affiliation: Reproductive Medical Center (L.F., Y.-P.S.), The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China 450052; and Department of Obstetrics and Gynaecology (H.-M.C., J.-C.C., P.C.K.L.), Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Fang
authors.forename: Hsun-Ming
authors.initials: HM
authors.lastname: Chang
authors.forename: Jung-Chien
authors.initials: JC
authors.lastname: Cheng
authors.forename: Peter C K
authors.initials: PC
authors.lastname: Leung
authors.forename: Ying-Pu
authors.initials: YP
authors.lastname: Sun
mesh_terms: D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism*; D011374:Progesterone / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D051900:Smad3 Protein / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D010750:Phosphoproteins; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D000098682:Steroidogenic Acute Regulatory Protein; D011374:Progesterone