Excessive cortisol level contributes to endometrial insulin resistance in PCOS
Polycystic ovary syndrome (PCOS) patients with insulin resistance (IR) have decreased oxidation of cortisol and defects of insulin signaling in the endometrium, a recent study has shown.
In addition, local cortisol elevation, derived from the reduction of 11β-hydroxysteroid dehydrogenases (11β-HSDs) 2, may influence the development of endometrial IR through the inhibition of the insulin signaling pathway via induction of phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression in endometrial epithelial cells (EECs), according to the authors.
There was an elevated cortisol concentration and a diminished 11β-HSD2 expression in endometrial biopsies obtained from PCOS patients with IR compared with those from non-PCOS and PCOS patients without IR.
PCOS patients with IR had a relatively impaired implantation rate and a defective endometrial insulin signaling pathway. Cortisol also lessened insulin-stimulated glucose uptake in EECs, which was mediated by inhibition of Akt phosphorylation and glucose transporter type 4 translocation via induction of PTEN.
The authors sought to determine whether the abundance of 11β-HSD1 and 11β-HSD2 and cortisol, as well as the insulin signaling pathway, are altered in PCOS endometrium, and to clarify the association between endometrial IR and local cortisol.
Cortisol and cortisone concentrations, 11β-HSD1 and 11β-HSD2, and core insulin signaling molecules in endometrial biopsies collected from non-PCOS and PCOS patients with or without IR on the 7th day after human chorionic gonadotropin injection were measured. The authors analysed the effects of cortisol on glucose uptake and the insulin signaling pathway in primary cultured EECs.