Dipeptidyl peptidase 4 serum activity and concentration are increased in women with polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) is a complex disease, the aetiology of which is not well understood. Alterations in potential candidate genes involved in the biosynthesis and metabolism of androgens, folliculogenesis and insulin and glucose metabolism have been suggested as possible aetiologies. Dipeptidyl peptidase-4 (DPP4) plays a key role in glucose homoeostasis and, thus, in the regulation of insulin secretion. The aim of our study was to analyse the DPP4 activity and concentrations in the serum of PCOS and non-PCOS patients and, additionally, study the activation of the DPP4 promoter by androgens in vitro. Serum samples were obtained from 288 female patients treated at the Center for Reproductive Medicine and Andrology (154 non-PCOS and 134 patients with PCOS). DPP4 activity was measured by the conversion of the DPP4 substrate Gly-Pro p-nitroanilide hydrochloride and DPP4 concentration with a commercial ELISA. Luciferase reporter assays, qPCR and Western Blot analyses were performed for the in vitro evaluation of the activation of the DPP4 promoter by androgens. DPP4 serum activity was increased in women with PCOS, regardless of which Rotterdam criteria led to the PCOS diagnosis. Furthermore, DPP4 serum levels were strongly correlated with the anti-Müllerian hormone (AMH) serum level. In vitro, the DPP4 promoter was stimulated by androgens in luciferase reporter assays, and DPP4 mRNA expression was increased in KGN granulosa carcinoma cells after androgen treatment. The results suggested that a deregulation of DPP4 serum levels could be an additional characteristic of the metabolic imbalances associated with PCOS.