Cryptotanshinone Reverses Reproductive and Metabolic Disturbances in PCOS Model Rats via Regulating the Expression of CYP17 and AR.

Jin Yu,Danying Zhang,Zailong Cai,Li Hao,Chaoqin Yu,Lingling Bai,Dongxia Zhai

doi:10.1155/2014/670743

Abstract

Objective. To explore the effect of Cryptotanshinone on reversing the reproductive and metabolic disturbances in polycystic ovary syndrome (PCOS) model rats and the possible regulatory mechanisms. Methods. PCOS model rats were induced by subcutaneous injection of dehydroepiandrosterone (DHEA) and verified by histological screening of vaginal exfoliated cells. After Cryptotanshinone intervention, the rats' body weight and ovary morphological were observed; the serum biochemical assessments were analyzed by radioimmunoassay (RIA) and key genes and proteins related with anabolism of androgen and insulin were detected by Real-Time PCR and Immunohistochemical (IHC). Results. The estrous cyclicity of PCOS model rats was significantly recovered by Cryptotanshinone. The body weight, ovarian coefficient, and ovarian morphology had been improved and the serum biochemical indicators including testosterone (T), androstenedione (A2), luteinizing hormone (LH), LH/follicle stimulating hormone (FSH), sexual binding globulin (SHBG), low density cholesterol (LDL-C), fasting insulin (FINS) were reversed after Cryptotanshinone intervention. Specifically, the levels of Cytochrome P450, 17-a hydroxylase/17,20 lyase (CYP17), and androgen receptor (AR) were downregulated significantly. Conclusions. Our data suggest that Cryptotanshinone could rebalance reproductive and metabolic disturbances in PCOS model rats and could be a potential therapeutic agent for the treatment of PCOS.

Highlights

Polycystic ovary syndrome (PCOS), a complex genetic condition, is a highly prevalent heterogeneous syndrome of clinical and/or biochemical hyperandrogenism, oligoanovulation, and polycystic ovaries (PCO), excluding other endocrinopathies according to the 2003 Rotterdam criteria [1, 2]
Women with PCOS are at increased risk of reproductive abnormalities, and two-thirds of them have metabolic dysfunction and, thereby, have an increased risk of developing type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) [3]
After being injected with DHEA for 20 days, the estrous cyclicity of 25 rats was in disorder in DHEA-ed group (40 rats in all), and the success rate of PCOS rat model induced by DHEA was 62.50%

Summary

Introduction

Polycystic ovary syndrome (PCOS), a complex genetic condition, is a highly prevalent heterogeneous syndrome of clinical and/or biochemical hyperandrogenism, oligoanovulation, and polycystic ovaries (PCO), excluding other endocrinopathies according to the 2003 Rotterdam criteria [1, 2]. Women with PCOS are at increased risk of reproductive abnormalities, and two-thirds of them have metabolic dysfunction and, thereby, have an increased risk of developing type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) [3]. The therapy of reversing the high level of androgen and improving the insulin sensitivity is significant for PCOS patients. In traditional Chinese medicine, Cryptotanshinone has been widely prescribed for several pathologies, including acne, cardiovascular, and some endocrine metabolic diseases such as diabetes [5].

Methods

Results

Conclusion