title: Anti-Müllerian hormone reduces follicle sensitivity to follicle-stimulating hormone in human granulosa cells.
abstract: OBJECTIVE
  To determine that anti-Müllerian hormone (AMH) has been shown to inhibits E(2) production in rodents and in luteinized granulosa cells (GC). We determined whether this occurs in human cells most highly expressing AMH (i.e., from small antral follicles) and whether this is an effect on aromatase promoter activity. We also investigated the effects of AMH on other factors determining FSH sensitivity.
  
  
  METHODS
  Granulosa cells were exposed to AMH with and without gonadotropins for 48 hours.
  
  
  METHODS
  University laboratory.
  
  
  METHODS
  Not applicable.
  
  
  METHODS
  None.
  
  
  METHODS
  Aromatase and FSH receptor messenger RNA expression measured using real time quantitative polymerase chain reaction (PCR). Aromatase promoter II activity measured using a luciferase assay. Estradiol, inhibin A and B, and vascular endothelial growth factor production were measured in the conditioned medium.
  
  
  RESULTS
  The AMH decreased gonadotropin-stimulated aromatase expression and decreased forskolin-stimulated aromatase in KGN cells and this effect was through a dose-dependent inhibition of promoter II. Surprisingly, AMH also reduced FSH receptor mRNA expression. High AMH doses had no effect on inhibin B, whereas a low dose stimulated production. There was no effect on inhibin A or vascular endothelial growth factor.
  
  
  CONCLUSIONS
  The AMH inhibits factors affecting FSH sensitivity. As AMH levels decrease with follicle growth, this inhibition would be removed. The AMH overproduction in anovulatory polycystic ovaries (PCO) may therefore restrict folliculogenesis by an inhibitory effect on FSH sensitivity, thereby contributing to anovulation.
authors.affiliation: Biomedical Sciences, St George's, University of London, London, United Kingdom. lpellatt@sgul.ac.uk
authors.forename: Laura
authors.initials: L
authors.lastname: Pellatt
authors.forename: Suman
authors.initials: S
authors.lastname: Rice
authors.forename: Nafi
authors.initials: N
authors.lastname: Dilaver
authors.forename: Amira
authors.initials: A
authors.lastname: Heshri
authors.forename: Raymond
authors.initials: R
authors.lastname: Galea
authors.forename: Mark
authors.initials: M
authors.lastname: Brincat
authors.forename: Kristy
authors.initials: K
authors.lastname: Brown
authors.forename: Evan R
authors.initials: ER
authors.lastname: Simpson
authors.forename: Helen D
authors.initials: HD
authors.lastname: Mason
mesh_terms: D054304:Anti-Mullerian Hormone / Q000378:metabolism*; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D017930:Genes, Reporter; D006107:Granulosa Cells / Q000378:metabolism*; D006801:Humans; D007265:Inhibins / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D006080:Ovarian Follicle / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011962:Receptors, FSH / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D011962:Receptors, FSH; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C422362:inhibin A; C422364:inhibin B; D004958:Estradiol; D007265:Inhibins; D054304:Anti-Mullerian Hormone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D001141:Aromatase