Role of insulin and insulin-like growth factor I receptor expression in the pathogenesis of genital endometriosis

Abstract

BACKGROUND: Growth factors play an important role in the pathogenesis of genital endometriosis. Insulin and insulin-like growth factors are involved in mitosis and differentiation in the endometrium during the menstrual cycle and early pregnancy, and are likely to indirectly affect the invasion of the endometrium during retrograde menstruation and the development of pain syndrome in endometriosis. However, the available literature data on insulin-like growth factors and insulin in the endometrium and endometrioid heterotopies in patients with genital endometriosis are scarse and contradictory.

AIM: The aim of this study was to investigate the expression of insulin receptors and insulin-like growth factor I receptors in the eutopic endometrium and endometrioid heterotopies of patients with genital endometriosis.

MATERIALS AND METHODS: This cross-sectional study included immunohistochemical analysis of surgical material obtained from two groups of women in the proliferative phase of the menstrual cycle: patients with endometriosis who received surgical treatment (endometrium and endometrioid heterotopies) and patients without endometriosis who were examined due to infertility (endometrium). The study also included investigation of carbohydrate metabolism (glucose tolerance test) and determination of blood serum insulin-like growth factor I, insulin and sex hormone levels. The material was stained to detect the expression of insulin receptors and insulin-like growth factor I receptors. Then, the relative area and optical density of the receptor expression were determined and the obtained data were analyzed statistically.

RESULTS: We analyzed the examination results of 131 women matched in age and weight and height characteristics: 101 patients with genital endometriosis and 30 patients in the control group. Carbohydrate metabolism was characterized by a 2.1-fold increase in glucose-stimulated insulin secretion in patients with genital endometriosis compared with the control subjects. The blood level of insulin-like growth factor I did not differ in the study groups. Statistically significant differences in receptor expression were obtained between the groups. In the endometrium of patients with genital endometriosis, the optical density of insulin receptors was lower (p = 0.007) and the expression of insulin-like growth factor I receptors higher (p = 0.002) compared to the endometrium of the control subjects. The median values of insulin receptor expression in endometrioid heterotopies were decreased compared to the endometrium of the control group (p < 0.001). The expression of insulin-like growth factor I receptors in endometrioid heterotopies was reduced compared to the endometrium of the same patients (p < 0.001).

CONCLUSIONS: The data obtained indicate significant features in the functioning of the insulin / insulin-like growth factor I system in patients with genital endometriosis: glucose-stimulated insulin secretion and relative endometrial insulin resistance due to the decreased expression of insulin receptors and the increased expression of insulin-like growth factor I receptors in the endometrium.

Keywords

endometriosis / insulin / insulin receptors / insulin-like growth factor I receptors / immunohistochemistry

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