Cryptotanshinone reverses ovarian insulin resistance in mice through activation of insulin signaling and the regulation of glucose transporters and hormone synthesizing enzymes

Fertil Steril. 2014 Aug;102(2):589-596.e4. doi: 10.1016/j.fertnstert.2014.05.012. Epub 2014 Jun 25.

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.

Design: Animal model and in vitro tissue model.

Setting: University-affiliated laboratory.

Animal(s): Mice.

Intervention(s): 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.

Main outcome measure(s): Ovarian glucose uptake, in vivo ovulation rate, serum and culture medium steroid level, and molecular expression of phosphatidylinositol 3-hydroxy kinase and steroidogenic enzymes.

Result(s): 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.

Conclusion(s): 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.

Keywords: Chinese medicine; PCOS; cryptotanshinone; insulin resistance; ovary.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Dexamethasone
  • Disease Models, Animal
  • Estradiol / blood
  • Female
  • Gene Expression Regulation, Enzymologic
  • Glucose Metabolism Disorders / blood
  • Glucose Metabolism Disorders / chemically induced
  • Glucose Metabolism Disorders / drug therapy*
  • Glucose Metabolism Disorders / enzymology
  • Glucose Metabolism Disorders / genetics
  • Glucose Metabolism Disorders / physiopathology
  • Glucose Transport Proteins, Facilitative / drug effects*
  • Glucose Transport Proteins, Facilitative / metabolism
  • Insulin / metabolism*
  • Insulin Resistance*
  • Mice
  • Ovary / drug effects*
  • Ovary / enzymology
  • Ovary / physiopathology
  • Ovulation / drug effects
  • Phenanthrenes / pharmacology*
  • Phosphatidylinositol 3-Kinase / metabolism
  • Polycystic Ovary Syndrome / blood
  • Polycystic Ovary Syndrome / chemically induced
  • Polycystic Ovary Syndrome / enzymology
  • Polycystic Ovary Syndrome / genetics
  • Polycystic Ovary Syndrome / physiopathology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects*
  • Steroid 17-alpha-Hydroxylase / genetics
  • Steroid 17-alpha-Hydroxylase / metabolism
  • Testosterone / blood
  • Tissue Culture Techniques

Substances

  • Blood Glucose
  • Glucose Transport Proteins, Facilitative
  • Insulin
  • Phenanthrenes
  • Testosterone
  • Estradiol
  • cryptotanshinone
  • Dexamethasone
  • Steroid 17-alpha-Hydroxylase
  • Phosphatidylinositol 3-Kinase
  • Akt2 protein, mouse
  • Proto-Oncogene Proteins c-akt