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

2021 ◽  
Vol 70 (3) ◽  
pp. 65-74
Author(s):  
Margarita S. Florova ◽  
Maria I. Yarmolinskaya ◽  
Natalya N. Tkachenko ◽  
Gulrukhsor Kh. Tolibova ◽  
Tatyana G. Tral

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.

2004 ◽  
Vol 122 (6) ◽  
pp. 931-937 ◽  
Author(s):  
Luigi Schips ◽  
Richard Zigeuner ◽  
Manfred Ratschek ◽  
Peter Rehak ◽  
Josef Rüschoff ◽  
...  

2006 ◽  
Vol 66 (13) ◽  
pp. 6570-6578 ◽  
Author(s):  
Cynthia M. van Golen ◽  
Tracy S. Schwab ◽  
Bhumsoo Kim ◽  
Mary E. Soules ◽  
Sang Su Oh ◽  
...  

1993 ◽  
Vol 137 (2) ◽  
pp. 223-230 ◽  
Author(s):  
D. L. Hadsell ◽  
C. R. Baumrucker ◽  
R. S. Kensinger

ABSTRACT The objectives of these studies were to determine if the concentration of insulin-like growth factor-I (IGF-I) in mammary colostrum secretions could be altered through manipulation of IGF-I concentrations in blood and to compare the temporal changes of IGF-I in mammary secretions to those occurring for IgG1. Milking of 15 pregnant Holstein cows was stopped at 8 weeks prepartum and they were randomly assigned to one of three treatments. A control (C) treatment consisted of feeding the animals 100% of NRC requirements for protein and energy. A second group of cows was fed as the control group and injected with 1·8 μmol bovine GH/day. The third group was fed at 70% of NRC requirements for protein and energy to cause a moderate nutrient restriction (NR). Body weight was measured weekly. Blood was collected by tail venepuncture at 4 h intervals for 24 h. Mammary secretions were collected and pooled among contralateral front and rear quarters (diagonal) for measurement of volume, IGF-I and IgG1 concentrations. Samples were collected at −7, −5, −2, 0 and 1 week postpartum. Cows on the NR treatment failed to gain weight during the dry period compared with C cows (P < 0·05). Blood GH and IGF-I concentrations (P > 0·1) were unaffected by NR treatment. Cows treated with GH had higher (P < 0·01) serum GH and IGF-I levels throughout the entire treatment period, and higher serum IgG1 at 5 and 2 weeks prepartum (P < 0·01). Total mass of IGF-I secreted per diagonal averaged 3·6-fold greater for GH-treated cows during the prepartum period than C and NR cows (P < 0·01). The concentration of IGF-I in mammary secretions was not affected by treatment during the prepartum period, but was 40% greater (P < 0·05) in GH-treated cows than C and NR cows at parturition. Analysis of a selective index comparing IGF-I secretion with that of IgG1 suggested that IGF-I does not enter mammary secretions by passive diffusion from blood. Journal of Endocrinology (1993) 137, 223–230


Development ◽  
1990 ◽  
Vol 108 (3) ◽  
pp. 491-495
Author(s):  
R. Spaventi ◽  
M. Antica ◽  
K. Pavelic

Growth factors have an important role in the regulation of cell growth, division and differentiation. They are also involved in the regulation of embryonic growth and differentiation. Insulin and insulin-like growth factor I (IGF I) play an important part in these events in the later stages of embryogenesis, when organogenesis is completed. In this study, we are presenting evidence that insulin and IGF I are also secreted by embryonic tissues during the prepancreatic stage of mouse development. We found measurable amounts of insulin and IGF I in 8- to 12-day-old mouse embryos. We also showed that embryonic cells derived from 8-, 9- and 10-day-old mouse embryos secrete insulin, IGF I and/or related molecules. Furthermore, the same growth factors, when added to the culture of 9-day-old mouse embryonic cells, stimulate their proliferation. These results lead to the conclusion that insulin can stimulate the growth of embryonic cells during the period when pancreas is not yet formed, which is indirect evidence for a paracrine (or autocrine) type of action.


1993 ◽  
Vol 290 (2) ◽  
pp. 419-426 ◽  
Author(s):  
M A Soos ◽  
C E Field ◽  
K Siddle

Hybrid insulin/insulin-like growth factor-I (IGF-I) receptors have previously been described in human placenta, but it has not been possible to study their properties in the presence of classical insulin receptors and type I IGF receptors. To facilitate the purification of hybrids, we produced an anti-peptide monoclonal antibody IGFR 1-2, directed against the C-terminal peptide of the type I IGF receptor beta-subunit. The antibody bound native human and rat type I IGF receptors, and reacted specifically with the beta-subunit on immunoblots. Solubilized placental microsomal membranes were depleted of classical type I IGF receptors by incubation with an immobilized monoclonal antibody IGFR 24-55, which reacts well with type I receptors but very poorly with hybrid receptors. Residual hybrid receptors were then isolated by incubation with immobilized antibody IGFR 1-2, and recovered by elution with excess of synthetic peptide antigen. Binding properties of hybrids were compared with those of immuno-affinity-purified insulin receptors and type I IGF receptors, by using the radioligands 125I-IGF-I and 125I-insulin. Hybrids bound approx. 20 times as much 125I-IGF-I as 125I-insulin at tracer concentrations (approx. 0.1 nM). The binding of 125I-insulin, but not 125I-IGF-I, to hybrids increased after treatment with dithiothreitol to reduce disulphide bonds between the alpha-subunits. Hybrids behaved very similarly to type I receptors with respect to the inhibition of 125I-IGF-I binding by unlabelled IGF-I and insulin. By contrast, the affinity of hybrids for insulin was approx. 10-fold lower than that of classical insulin receptors, as assessed by inhibition of 125I-insulin binding by unlabelled hormone. It is concluded that the properties of insulin receptors, but not IGF receptors, are markedly affected by assembly as hybrid compared with classical structures, and that hybrids are more likely to be responsive to IGF-I than insulin under physiological conditions.


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