Local Cortisol Elevation Contributes to Endometrial Insulin Resistance in Polycystic Ovary Syndrome.

Local Cortisol Elevation Contributes to Endometrial Insulin Resistance in Polycystic Ovary Syndrome.

J Clin Endocrinol Metab. 2018 Mar 30;:

Authors: Qi J, Wang W, Zhu Q, He Y, Lu Y, Wang Y, Li X, Chen ZJ, Sun Y

Abstract
Context: Endometrial insulin resistance may account for the endometrial dysfunction in polycystic ovary syndrome (PCOS). The underlying mechanism remains to be elucidated.
Objective: To investigate whether the abundance of 11β-hydroxysteroid dehydrogenases (11β-HSD1 and -2) and cortisol as well as the insulin signaling pathway are altered in PCOS endometrium and to clarify the relationship between endometrial insulin resistance (IR) and local cortisol.
Design: We measured cortisol and cortisone concentrations, 11β-HSD1 and -2, and core insulin signaling molecules in endometrial biopsies collected from non-PCOS and PCOS with or without IR patients on day hCG+7. We also studied the effects of cortisol on glucose uptake and the insulin signaling pathway in primary cultured endometrial epithelial cells (EECs).
Results: The cortisol concentration was elevated whereas 11β-HSD2 expression was diminished in endometrial biopsies obtained from PCOS with IR patients compared to those from non-PCOS and PCOS without IR patients. The implantation rate was relatively impaired and the endometrial insulin signaling pathway was defective in PCOS with IR patients. In addition, cortisol attenuated insulin-stimulated glucose uptake in EECs, which was mediated by inhibition of Akt phosphorylation and glucose transporter type 4 (GLUT4) translocation via induction of phosphatase and tensin homolog deleted on chromosome ten (PTEN).
Conclusions: Decreased oxidation of cortisol and defects of insulin signaling in endometrium were observed in PCOS with IR patients. The excessive cortisol level, derived from the reduction of 11β-HSD2, might contribute to the development of endometrial IR by inhibiting the insulin signaling pathway via induction of PTEN expression in EECs.

PMID: 29618067 [PubMed - as supplied by publisher]

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