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

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.

Correlation between glucose metabolism and serum steroid hormones in patients with polycystic ovary syndrome

“…Our previous study revealed that patients with PCOS had higher plasma glucose levels than their corresponding control groups. 16 In addition, the levels of several serum steroid hormones, such as DHEAS, 17-hydroprogesterone and oestrone, were different in lean and obese patients, indicating that androgen, androgen metabolites and other steroid hormones may play a role in the occurrence of obesity and abnormal glucose metabolism.…”

“…Previous studies have found that hyperandrogenism can induce insulin resistance in subcutaneous tissue by inhibiting the phosphorylation of protein kinase C, upregulating the uncoupling of protein‐1 expression in brown adipose tissue, or promoting lipolysis in visceral fat cells, thus influencing glucose metabolism. Our previous study revealed that patients with PCOS had higher plasma glucose levels than their corresponding control groups . In addition, the levels of several serum steroid hormones, such as DHEAS, 17‐hydroprogesterone and oestrone, were different in lean and obese patients, indicating that androgen, androgen metabolites and other steroid hormones may play a role in the occurrence of obesity and abnormal glucose metabolism.…”

“…The exclusion criteria included pregnancy, other related endocrine diseases, previous ovarian surgery and medication history that may affect steroid hormones within the previous 3 months. The detailed inclusion and exclusion criteria can be found in our previous study …”

“…The serum was separated and stored at −80°C for further analysis. Through a series of sample preparations as previously described, a total of 14 steroid hormones were extracted and measured, including 17‐hydroxyprogesterone, 17‐hydroxypregnenolone, progesterone, pregnenolone, cortisol, cortisone, 11‐deoxycortisol, 11‐deoxycorticorsterone, aldosterone, corticosterone, oestrone, androstenedione, DHEAS and testosterone. The details of LC/MS‐MS assay and clinical biochemistry methods are shown in the supplementary materials.…”

“…can be found in our previous study. 16 The study protocol was approved by the Ethics Committee of Ruijin Hospital and Renji Hospital, which are both affiliated with Shanghai Jiao Tong University School of Medicine. All subjects had a thorough understanding of the research procedures and signed an informed consent form.…”