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

Capsule:
The ability of murine ovarian hormone synthesis became abnormal and the ovarian tissue behaved insulin resistance, after treated with dexamethasone, in vivo and in vitro; the Chinese herbal extract cryptotanshinone was found to partially antagonize their behavior.

Authors:
Yangang Huang, M.D., Wei Li, M.D., Ronald Wang, M.D., Jianhua Zheng, M.D., XiaoKe Wu, M.D., Ph.D.

Volume 102, Issue 2, Pages 589–596.e4

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.

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