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Are growth factor receptors modulated by metformin in human endometrial stromal cells after stimulation with androgen and insulin?

  • Gynecologic Endocrinology and Reproductive Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Objective

To assess the effect of metformin on gene and protein expression of insulin receptor (IR) and IGF-1 (IGF-1R) receptor in human endometrial stromal cells after stimulation with androgen and insulin.

Study design

Primary culture of endometrial stromal cells stimulated with estrogen, progesterone with or without androgen or insulin, and treated with metformin for 24 and 48 h, followed by RNA (qRT-PCR) and protein (Western blot) extraction and analysis.

Results

IR gene expression was increased after treatment with insulin (2.9-fold change, p = 0.027) and further after metformin treatment (4.7-fold change, p < 0.001), and in IGF-1R, the group treated with insulin (1.83-fold change) and metformin (1.78-fold change) showed more expression, than control group (p < 0.001). Similarly, IR protein expression was increased after addition of metformin and insulin (249,869 ± 15,878) in relation to the other groups (p < 0.001). Furthermore, cells treated with insulin (153,634 ± 29,123) and androgen plus insulin (162,854 ± 86,258) had a higher IR protein expression compared to control (104,654 ± 5,634) and androgen group (71,595 ± 3,439, (p = 0.045 and 0.021). In groups treated with insulin (127,711 ± 4,591) and androgen plus insulin (151,098 ± 5,194) the protein IGF-1R was increased compared to control (79,355 ± 3,470) and the androgen-only group (79,326 ± 3,114) (p < 0.001).

Conclusion

Metformin in combination with insulin increased IR protein and gene expressions, while it had no influence on the protein expression of IGF-1R in endometrial stromal cells.

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Acknowledgments

This work had financial support from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, proc. 470636/2012-2), Programa de Pós-graduação em Ciências Biológicas—Fisiologia da UFRGS (PPGFISIO) and Fundo de Incentivo à Pesquisa e Eventos (FIPE) do Grupo de Pesquisa e Pós-Graduação (GPPG) do Hospital de Clínicas de Porto Alegre. Edison Capp, Ilma Simoni Brum da Silva, Gustavo Dias Ferreira and Tadeu Ludwig do Nascimento are scholarship recipients from CNPq. Amanda de Barros Machado is scholarship recipient from CAPES—Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.

Conflict of interest

The authors have no conflict of interest.

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Authors and Affiliations

  1. Laboratório de Biologia Molecular Endócrina e Tumoral, Departamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil

    Gustavo Dias Ferreira, Amanda de Barros Machado, Tadeu Ludwig do Nascimento, Ilma Simoni Brum, Helena von Eye Corleta & Edison Capp

  2. Laboratório de Ginecologia e Obstetrícia Molecular, Departamento de Ginecologia e Obstetrícia, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, UFRGS, Porto Alegre, Brazil

    Gustavo Dias Ferreira, Amanda de Barros Machado, Tadeu Ludwig do Nascimento, Ilma Simoni Brum, Helena von Eye Corleta & Edison Capp

  3. Department of Gynecological Endocrinology and Reproductive Medicine, University Hospital Heidelberg, Heidelberg, Germany

    Ariane Germeyer, Thomas Strowitzki & Edison Capp

  4. Serviço de Ginecologia e Obstetrícia, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350/11º andar, Porto Alegre, RS, CEP 90035-903, Brazil

    Helena von Eye Corleta & Edison Capp

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  1. Gustavo Dias Ferreira
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Correspondence to Edison Capp.

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Ferreira, G.D., Germeyer, A., de Barros Machado, A. et al. Are growth factor receptors modulated by metformin in human endometrial stromal cells after stimulation with androgen and insulin?. Arch Gynecol Obstet 290, 361–367 (2014). https://doi.org/10.1007/s00404-014-3197-5

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