title: Human granulosa cells: insulin and insulin-like growth factor-1 receptors and aromatase expression modulation by metformin.
abstract: OBJECTIVE
  Granulosa cells are the source of the most important ovarian steroids. Even in patients without significant improvement in metabolic parameters, metformin has apparently an important effect on the ovary. The aim of this study was to evaluate gene and protein expression of an insulin receptor (IR), insulin-like growth factor-1 (IGF1) receptor (IGF1R) and aromatase in granulosa cells treated with metformin and insulin.
  
  
  METHODS
  Luteinized granulosa cells were collected from 27 patients during in vitro fertilization procedures. Cells were isolated, stored in culture for 24 h and divided into four groups: control; metformin for 30 min, and metformin for 30 min plus insulin for 30 or 60 min.
  
  
  RESULTS
  IR and IGF1R mRNA expression was significantly enhanced by metformin but was not affected by insulin. Aromatase mRNA expression was significantly reduced in metformin-incubated cells following stimulation with insulin for 30 min. No statistical differences were found in IGF1R and aromatase protein expression, and IR expression was not detected.
  
  
  CONCLUSIONS
  A direct effect of metformin on the gene expression of IGF1R, IR and aromatase was observed. Further studies should investigate the role of IGF1R, IR and aromatase in ovarian physiology for a better understanding of the effect of metformin.
authors.affiliation: Núcleo de Reprodução Humana, Hospital Moinhos de Vento, Porto Alegre, Brazil.
authors.forename: Isabela Piva
authors.initials: IP
authors.lastname: Fuhrmeister
authors.forename: Gisele
authors.initials: G
authors.lastname: Branchini
authors.forename: Anita M
authors.initials: AM
authors.lastname: Pimentel
authors.forename: Gustavo Dias
authors.initials: GD
authors.lastname: Ferreira
authors.forename: Edison
authors.initials: E
authors.lastname: Capp
authors.forename: Ilma Simoni
authors.initials: IS
authors.lastname: Brum
authors.forename: Helena
authors.initials: H
authors.lastname: von Eye Corleta
mesh_terms: D000328:Adult; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D008687:Metformin / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D012333:RNA, Messenger; D008687:Metformin; D001141:Aromatase; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin