The upregulation of 11β-HSD1 in ovarian granulosa cells by cortisol and interleukin-1β in polycystic ovary syndrome

Abstract

Our previous study have demonstrated the elevated cortisol concentration in the follicular fluid (FF) contributed to the insulin resistance of the granulosa cells (GCs) in PCOS, but the complicated cortisol generation mechanisms are still unknown. 11β-hydroxysteroid type 1(11β-HSD1) mainly functions as reductase in intact cells, converting cortisone to cortisol. Cortisol and IL-1β are known to induce 11β-HSD1 in number of tissues, but few results were obtained in ovarian GCs In this study, FF and GCs from PCOS and non-PCOS patients were collected to study the interaction of cortisol and IL-1β in 11β-HSD1 expression. The ELISA and qRT-PCR revealed that the cortisol and IL-1β concentration in FF and 11β-HSD1 abundance in GCs were elevated in PCOS patients. By using cultured GCs in vitro, we demonstrated that both cortisol and IL-1β could stimulate 11β-HSD1 expression. The induction of 11β-HSD1 by IL-1β was further inducted by cortisol, whereas the induction of IL-1β and IL-6 expression by IL-1β was completely inhibited by cortisol. In conclusion, cortisol and IL-1β preformed a synergistically upregulation of 11β-HSD1 expression in GCs, contributing to the accumulation of cortisol in FF of PCOS patients. This may lead to the metabolic disorders of the ovary.