Effects of Electro-Acupuncture on Ovarian P450arom, P450c17α and mRNA Expression Induced by Letrozole in PCOS Rats

Jie Sun,Huirong Liu,Huangan Wu,Chunlan Jin,Yunhua Cui,Jimeng Zhao,Bing Zhu,Lingxiang Wu,Yin Shi,Jean-Marc A Lobaccaro

doi:10.1371/journal.pone.0079382

Abstract

Hyperandrogenism is a core factor in the series of reproductive and endocrine metabolic disorders involved in polycystic ovary syndrome (PCOS). Abnormalities in enzymatic activity and the expression of ovarian granular cell layer P450arom and theca cell P450c17α can lead to an atypical environment of local ovarian hormones, including excessive androgen levels. Rat models prepared with letrozole exhibit similar endocrine and histological changes to those that occur in human PCOS. We used such a model to study the role of electro-acupuncture (EA) in regulating ovarian P450arom and P450c17α enzymatic activity and mRNA expression in PCOS rats. Female Sprague Dawley (SD) rats aged 42 days were randomly divided into 3 groups (control, PCOS, and PCOS EA) consisting of 10 rats each. The PCOS and PCOS EA groups were administered a gavage of 1.0 mg/kg−1 of letrozole solution once daily for 21 consecutive days. Beginning in the ninth week, the PCOS EA group was administered low-frequency EA treatment daily for 14 consecutive days. After the treatment, we obtained the following results. The estrous cycles were restored in 8 of the 10 rats in the PCOS EA group, and their ovarian morphologies and ultrastructures normalized. The peripheral blood measurements (with ELISA) showed significantly decreased androgens (i.e., androstenedione and testosterone) with significantly increased estrogens (i.e., estrone, estradiol) and increased P450arom with decreased P450C17α. Immunohistochemistry and Western blotting methods showed enhanced expression of ovarian granular cell layer P450arom as well as decreased expression of theca cell layer P450C17α. Fluorescence quantitative PCR methods showed enhanced expression of ovarian granular cell layer P450arom mRNA as well as decreased expression of theca cell layer P450C17α mRNA. These results may help explain the effects of electro-acupuncture in changing the local ovarian hyperandrogenic environment and improving reproductive and endocrine metabolic disorders in PCOS.

Highlights

Polycystic ovary syndrome (PCOS) is a female reproductive and endocrine disease that results in follicular development and ovulation disorders because of steroid hormone imbalances
We have previously reported that acupuncture could significantly reduce the weights, body mass indices (BMIs), and waist-hip ratios (WHRs) of obese patients with PCOS; decrease their peripheral testosterone levels and the ratio of luteinizing hormone (LH) to follicle stimulating hormone (FSH); and improve insulin resistance and menstrual cycle and ovulation dysfunction [14]
Stener-Victorin et al found that low-frequency EA stimulation reduced estradiol valerate-induced ovarian nerve growth factor (NGF) [5], ovarian corticotropin-releasing factor (CRF) [6], and ovarian and hypothalamic endothelin-1 (ET-1) levels [7]

Summary

Introduction

Polycystic ovary syndrome (PCOS) is a female reproductive and endocrine disease that results in follicular development and ovulation disorders because of steroid hormone imbalances. The basic clinical and pathological features of PCOS are chronic persistent anovulation and hyperandrogenism, bilateral cystic enlargement of the ovaries (larger than normal ovaries in all follicle periods, including preantral), and significantly increased androgen levels with relatively insufficient estradiol in the peripheral blood [1]. EA can normalize a patient’s ovulation and menstrual cycles by affecting or improving hypothalamus, pituitary, and ovarian functions [11,12,13]. We have previously reported that acupuncture could significantly reduce the weights, body mass indices (BMIs), and waist-hip ratios (WHRs) of obese patients with PCOS; decrease their peripheral testosterone levels and the ratio of luteinizing hormone (LH) to follicle stimulating hormone (FSH); and improve insulin resistance and menstrual cycle and ovulation dysfunction [14]

Methods

Results

Conclusion