title: Modulation of gonadotrophin induced steroidogenic enzymes in granulosa cells by d-chiroinositol.
abstract: BACKGROUND
  d-chiroinositol (DCI) is a inositolphosphoglycan (IPG) involved in several cellular functions that control the glucose metabolism. DCI functions as second messenger in the insulin signaling pathway and it is considered an insulin sensitizer since deficiency in tissue availability of DCI were shown to cause insulin resistance (IR). Polycystic ovary syndrome (PCOS) is a pathological condition that is often accompanied with insulin resistance. DCI can positively affects several aspect of PCOS etiology decreasing the total and free testosterone, lowering blood pressure, improving the glucose metabolism and increasing the ovulation frequency. The purpose of this study was to evaluate the effects of DCI and insulin combined with gonadotrophins namely follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on key steroidogenic enzymes genes regulation, cytochrome P450 family 19 subfamily A member 1 (CYP19A1) and cytochrome P450 side-chain cleavage (P450scc) in primary cultures of human granulosa cells (hGCs). We also investigated whether DCI, being an insulin-sensitizer would be able to counteract the expected stimulator activity of insulin on human granulosa cells (hGCs).
  
  
  METHODS
  The study was conducted on primary cultures of hGCs. Gene expression was evaluated by RT-qPCR method. Statistical analysis was performed applying student t-test, as appropriate (P < 0.05) set for statistical significance.
  
  
  RESULTS
  DCI is able to reduce the gene expression of CYP19A1, P450scc and insulin-like growth factor 1 receptor (IGF-1R) in dose-response manner. The presence of DCI impaired the increased expression of steroidogenic enzyme genes generated by the insulin treatment in gonadotrophin-stimulated hGCs.
  
  
  CONCLUSIONS
  Insulin acts as co-gonadotrophin increasing the expression of steroidogenic enzymes genes in gonadotrophin-stimulated granulosa cells. DCI is an insulin-sensitizer that counteracts this action by reducing the expression of the genes CYP19A1, P450scc and IGF-1R. The ability of DCI to modulate in vitro ovarian activity of insulin could in part explain its beneficial effect when used as treatment for conditions associated to insulin resistance.
authors: Mother-Infant Department, University of Modena and Reggio Emilia, Via del pozzo 41, 41100, Modena, Italy.
authors: Sandro
authors: S
authors: Sacchi
authors: Mother-Infant Department, University of Modena and Reggio Emilia, Via del pozzo 41, 41100, Modena, Italy.
authors: Federica
authors: F
authors: Marinaro
authors: Mother-Infant Department, University of Modena and Reggio Emilia, Via del pozzo 41, 41100, Modena, Italy.
authors: Debora
authors: D
authors: Tondelli
authors: Mother-Infant Department, University of Modena and Reggio Emilia, Via del pozzo 41, 41100, Modena, Italy.
authors: Jessica
authors: J
authors: Lui
authors: Mother-Infant Department, University of Modena and Reggio Emilia, Via del pozzo 41, 41100, Modena, Italy.
authors: Susanna
authors: S
authors: Xella
authors: Mother-Infant Department, University of Modena and Reggio Emilia, Via del pozzo 41, 41100, Modena, Italy.
authors: Tiziana
authors: T
authors: Marsella
authors: Mother-Infant Department, University of Modena and Reggio Emilia, Via del pozzo 41, 41100, Modena, Italy.
authors: Daniela
authors: D
authors: Tagliasacchi
authors: Mother-Infant Department, University of Modena and Reggio Emilia, Via del pozzo 41, 41100, Modena, Italy.
authors: Cindy
authors: C
authors: Argento
authors: Mother-Infant Department, University of Modena and Reggio Emilia, Via del pozzo 41, 41100, Modena, Italy.
authors: Alessandra
authors: A
authors: Tirelli
authors: Mother-Infant Department, University of Modena and Reggio Emilia, Via del pozzo 41, 41100, Modena, Italy.
authors: Simone
authors: S
authors: Giulini
authors: University of Modena and Reggio Emilia and Clinica Eugin Modena, Modena, Italy. antlamarca@libero.it.
authors: Antonio
authors: A
authors: La Marca
mesh_terms: D000328:Adult; D001141:Aromatase / Q000096:biosynthesis*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods; D006062:Gonadotropins / Q000494:pharmacology*; D006107:Granulosa Cells / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D007294:Inositol / Q000494:pharmacology*; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis*
chemical_list: D006062:Gonadotropins; D007294:Inositol; D001141:Aromatase; C561410:CYP19A1 protein, human; D017526:Receptor, IGF Type 1
keywords: Insulin resistance; Steroiodogenesis; d-chiroinositol