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

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.