Steroid hormone profiling in obese and nonobese women with polycystic ovary syndrome

Yuying Deng,Lihua Wang,Lei Ye,Dandan Zhao,Jie Hong,Yifei Zhang,Shengxian Li,Tao Tao,Zuwei Yang,Junjie Gu,Weiqing Wang,Weiqiong Gu,Wenzhong Zhou,Wei Liu,Guang Ning

doi:10.1038/s41598-017-14534-2

Abstract

The study explored differences in the steroidogenic pathway between obese and nonobese women with polycystic ovary syndrome (PCOS) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). 1044 women with PCOS (including 350 lean, 312 overweight and 382 obese) and 366 control women without PCOS (including 203 lean, 32 overweight and 131 obese) were enrolled. The differences in steroid hormones were amplified in lean PCOS versus lean controls compared with obese PCOS versus obese controls. Compared with obese PCOS, lean PCOS demonstrated increased dehydroepiandrosterone sulfate (P = 0.015), 17-hydropregnenolone (P = 0.003), 17-hydroprogesterone (17-OHP) (P < 0.001), progesterone (P < 0.001) and estrone (P < 0.001) levels. Enzyme activity evaluation showed that lean PCOS had increased activity of P450c17 (17-hydropregnenolone/pregnenolone, P < 0.001), P450aro (P < 0.001), 3βHSD2 (progesterone/ pregnenolone and 17-OHP/17-hydropregnenolone, both P < 0.001) and decreased activity of P450c21(11-deoxycorticorsterone/progesterone and 11-deoxycortisol/17-OHP, P < 0.001). Moreover, we found higher frequencies of CYP21A2- (encoding P450c21) c.552 C > G (p. D184E) in lean PCOS compared with obese PCOS patients (P = 0.006). In conclusion, this study demonstrated for the first time that the adrenal-specific enzyme P450c21 showed decreased activity in lean PCOS patients, and that the adrenal androgen excess may play different roles in lean and obese PCOS patients, which represents as different enzyme activity in the steroidogenic pathway.

Highlights

The study explored differences in the steroidogenic pathway between obese and nonobese women with polycystic ovary syndrome (PCOS) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). 1044 women with PCOS and 366 control women without PCOS were enrolled
The present study is the first to conduct a thorough comparison of steroid hormones between obese and nonobese PCOS patients. 14 steroid hormones were measured in 1044 PCOS patients and 366 controls using LC-MS/MS
Differences in steroid hormones were amplified in the lean PCOS patient versus the lean controls compared with the obese PCOS patients versus the obese controls

Summary

Introduction

The study explored differences in the steroidogenic pathway between obese and nonobese women with polycystic ovary syndrome (PCOS) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). 1044 women with PCOS (including 350 lean, 312 overweight and 382 obese) and 366 control women without PCOS (including 203 lean, 32 overweight and 131 obese) were enrolled. A negative association between DHEAS and BMI or fasting insulin among PCOS patients has been reported by Kumar et al.[9] and Moran et al.[10], suggesting that the proportion of adrenal androgen excess may be higher in nonobese PCOS patients These studies have mainly focused on the end-product of adrenal androgen synthesis, while the changes in the intermediate steroid hormones, and www.nature.com/scientificreports/. In the present study, we measured 14 steroid hormones in PCOS patients and controls, using liquid chromatography-tandem mass spectrometry (LC-MS/MS), which has been recommended by the Endocrine Society and has shown high sensitivity for steroid assay[11,12,13], to explore the different profiles of steroid hormone and enzyme activity in the steroidogenic pathways of obese and nonobese PCOS patients.

Methods

Results

Conclusion