Characterization of receptors for insulin-like growth factor type I on cultured human endometrial stromal cells: downregulation by progesterone

Strowitzki, T.; Singer, Gamal A. M.; Rettig, Ingo; Capp, Edison

doi:10.3109/09513599609012314

Cited by 9 publications

(4 citation statements)

References 20 publications

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“…We have here extended these data to show the distribution of the protein through the normal cycle and, most importantly, its expression in mid secretory luminal epithelium. Direct evidence for hormonal control of IGF1R expression comes from studies in isolated human endometrial cells that report IGF1R downregulation by progesterone (Strowitzki et al, 1996). In rats, IGF1R expression in the uterus is enhanced by estrogen treatment (Ghahary and Murphy, 1989) and in baboons, expression at the glandular and luminal epithelium undergoes cyclic changes and is upregulated by estrogen (Hild-Petito et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

miR-145 suppresses embryo–epithelial juxtacrine communication at implantation by modulating maternal IGF1R

Kang¹,

Lees²,

Matthews³

et al. 2015

Development

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Successful implantation requires the synchronization of viable embryonic development with endometrial receptivity. The mechanisms allowing for the initiation of crosstalk between the embryo and the endometrium remain elusive; however, recent studies have revealed that there are alterations in endometrial microRNAs (miRs) in women suffering repeated implantation failure and that one of the altered miRs is miR-145. We assessed the role of miR-145 and its target IGF1R, in early implantation. miR-145 overexpression and IGF1R knockdown were achieved in Ishikawa endometrial cells. Quantitative PCR, western blotting and 39UTR luciferase reporter assays confirmed that IGF1R is a direct target of miR-145 in the endometrium. Attachment of mouse embryos or IGF1-coated beads to endometrial epithelial cells was used to study the effects of altered miR-145 and/or IGF1R expression on early implantation events. miR-145 overexpression or specific reduction of IGF1R impaired attachment in both cases. An IGF1R target protector prevented the miR-145-mediated reduction in IGF1R and reversed the effect of miR-145 overexpression on attachment. The data demonstrate that miR-145 influences embryo attachment by reducing the level of IGF1R in endometrium.

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Section: Discussionmentioning

confidence: 99%

miR-145 suppresses embryo–epithelial juxtacrine communication at implantation by modulating maternal IGF1R

Kang¹,

Lees²,

Matthews³

et al. 2015

Development

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“…IGF-IR is localized to the luminal and glandular epithelium as well as the stroma, and its expression is down-regulated by progesterone (19,20). In endometrial cells, the activity of the phosphoinositide-3-kinase/Akt pathway is also critically regulated by the activity of phosphatase and tensin homologue deleted on chromosome 10 (PTEN), a lipid phosphatase that negatively regulates phosphoinositide-3-kinase activity by the dephosphorylation of phosphoinositol (3,4,5) triphosphate (21).…”

mentioning

confidence: 99%

Overexpression of the Insulin-Like Growth Factor I Receptor and Activation of the AKT Pathway in Hyperplastic Endometrium

McCampbell

Broaddus

Loose

et al. 2006

Clinical Cancer Research

119

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Purpose: Although there is considerable information on the molecular aberrations associated with endometrial cancer, very little is known of the changes in gene expression associated with endometrial hyperplasia. Experimental Design: To address this, we have compared the level of expression of estrogenregulated genes and components of the insulin-like growth factor I (IGF-I) signaling pathway in endometrial biopsies from subjects with normal endometrium, complex atypical endometrial hyperplasia, and endometrial adenocarcinoma (type I).Results: There was a significant increase in the expression of the IGF-I receptor (IGF-IR) in biopsies from hyperplastic endometrium and endometrial carcinoma compared with the proliferative endometrium. The receptor was also activated, as judged by increased tyrosine phosphorylation. In addition, in endometrial hyperplasia and carcinoma, the downstream components of the IGF-IR pathway are activated, as reflected in increased Akt phosphorylation. Loss of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) expression in endometrial hyperplasia did not correlate with increased activation of IGF-IR. However, the simultaneous loss of PTEN expression and increased IGF-IR activation in hyperplasia was associated with an increased incidence of endometrial carcinoma. Conclusions: These results suggest that up-regulation of IGF-IR and loss of PTEN may be independent events that give rise to complementary activation of the IGF-I pathway and increase the probability of the development of cancer. These studies suggest that increased expression of IGF-IR may be an important contributor to the risk of endometrial hyperplasia and cancer.

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“…IGF-1 activity is altered during the menstrual cycle. Strowitzki et al (7) demonstrated that the number of IGF-1 receptors is not cycle de- (10,11). In summary, the results of this study suggest that IGF-BP could modulate the action of IGF-1 throughout the menstrual cycle, and its higher concentration in the progestogenic phase may play a role in the implantation process.…”

Section: Discussionmentioning

confidence: 47%

Cycle modulation of insulin-like growth factor-binding protein 1 in human endometrium

Corleta

Capp

Strowitzki

2000

Braz J Med Biol Res

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Endometrium is one of the fastest growing human tissues. Sex hormones, estrogen and progesterone, in interaction with several growth factors, control its growth and differentiation. Insulin-like growth factor 1 (IGF-1) interacts with cell surface receptors and also with specific soluble binding proteins. IGF-binding proteins (IGF-BP) have been shown to modulate IGF-1 action. Of six known isoforms, IGF-BP-1 has been characterized as a marker produced by endometrial stromal cells in the late secretory phase and in the decidua. In the current study, IGF-1-BP concentration and affinity in the proliferative and secretory phase of the menstrual cycle were measured. Endometrial samples were from patients of reproductive age with regular menstrual cycles and taking no steroid hormones. Cytosolic fractions were prepared and binding of 125 I-labeled IGF-1 performed. Crosslinking reaction products were analyzed by SDS-polyacrylamide gel electrophoresis (7.5%) followed by autoradiography. 125 I-IGF-1 affinity to cytosolic proteins was not statistically different between the proliferative and secretory endometrium. An approximately 35-kDa binding protein was identified when 125 I-IGF-1 was cross-linked to cytosol proteins. Secretory endometrium had significantly more IGF-1-BP when compared to proliferative endometrium. The specificity of the cross-linking process was evaluated by the addition of 100 nM unlabeled IGF-1 or insulin. Unlabeled IGF-1 totally abolished the radioactivity from the band, indicating specific binding. Insulin had no apparent effect on the intensity of the labeled band. These results suggest that IGF-BP could modulate the action of IGF-1 throughout the menstrual cycle. It would be interesting to study this binding protein in other pathologic conditions of the endometrium such as adenocarcinomas and hyperplasia.

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Characterization of receptors for insulin-like growth factor type I on cultured human endometrial stromal cells: downregulation by progesterone

Cited by 9 publications

References 20 publications

miR-145 suppresses embryo–epithelial juxtacrine communication at implantation by modulating maternal IGF1R

miR-145 suppresses embryo–epithelial juxtacrine communication at implantation by modulating maternal IGF1R

Overexpression of the Insulin-Like Growth Factor I Receptor and Activation of the AKT Pathway in Hyperplastic Endometrium

Cycle modulation of insulin-like growth factor-binding protein 1 in human endometrium

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