title: Cryptotanshinone reverses ovarian insulin resistance in mice through activation of insulin signaling and the regulation of glucose transporters and hormone synthesizing enzymes.
abstract: OBJECTIVE
  To investigate the effects of cryptotanshinone (CRY), an active component of Chinese medicine, on ovarian androgen production, insulin resistance (IR), and glucose metabolism in mice.
  
  
  METHODS
  Animal model and in vitro tissue model.
  
  
  METHODS
  University-affiliated laboratory.
  
  
  METHODS
  Mice.
  
  
  METHODS
  Ovarian IR was induced by dexamethasone (DEX) in vivo. Animals were randomized to receive CRY treatment for 3 days or not. Ovulation rates, serum steroid levels, and glucose uptake in ovaries were quantified, and proteins in the phosphatidylinositol 3-hydroxy kinase pathway were measured. In vitro ovarian IR was also induced by DEX for 3 days. Ovarian steroid hormone secretion and glucose uptake were measured, and the hormone-synthesizing enzymes were determined by semiquantitative reverse transcription-polymerase chain reaction.
  
  
  METHODS
  Ovarian glucose uptake, in vivo ovulation rate, serum and culture medium steroid level, and molecular expression of phosphatidylinositol 3-hydroxy kinase and steroidogenic enzymes.
  
  
  RESULTS
  Dexamethasone significantly increased ovulation rates in vivo and increased T and E2 production and decreased ovarian glucose uptake in vivo and in vitro. Cryptotanshinone significantly reduced ovulation rates in vivo and decreased T and estrogen production in vitro. Cryptotanshinone attenuated the inhibition of DEX on AKT2 and suppressed the up-regulation of CYP11 and CYP17 expression by DEX.
  
  
  CONCLUSIONS
  Cryptotanshinone reversed DEX-induced androgen excess and ovarian IR in mice through activation of insulin signaling and the regulation of glucose transporters and hormone-synthesizing enzymes. This suggests a potential role for CRY in treating the ovulatory dysfunction associated with PCOS.
authors: Department of Obstetrics and Gynecology, First Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
authors: Yangang
authors: Y
authors: Huang
authors: Department of Obstetrics and Gynecology, The First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin.
authors: Wei
authors: W
authors: Li
authors: Department of Obstetrics and Gynecology, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.
authors: Chi Chiu
authors: CC
authors: Wang
authors: Department of Obstetrics and Gynecology, The First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin.
authors: Xiaoke
authors: X
authors: Wu
authors: Department of Obstetrics and Gynecology, First Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China. Electronic address: Prof.j.zheng@gmail.com.
authors: Jianhua
authors: J
authors: Zheng
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone; D004195:Disease Models, Animal; D004958:Estradiol / Q000097:blood; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D044882:Glucose Metabolism Disorders / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D051246:Glucose Transport Proteins, Facilitative / Q000187:drug effects* / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D051379:Mice; D010053:Ovary / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D010060:Ovulation / Q000187:drug effects; D010616:Phenanthrenes / Q000494:pharmacology*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D046509:Tissue Culture Techniques
chemical_list: D001786:Blood Glucose; D051246:Glucose Transport Proteins, Facilitative; D007328:Insulin; D010616:Phenanthrenes; D013739:Testosterone; D004958:Estradiol; C037886:cryptotanshinone; D003907:Dexamethasone; D013254:Steroid 17-alpha-Hydroxylase; D058539:Phosphatidylinositol 3-Kinase; C494922:Akt2 protein, mouse; D051057:Proto-Oncogene Proteins c-akt
keywords: Chinese medicine; PCOS; cryptotanshinone; insulin resistance; ovary