Abstract
Objective
Our objective was to determine the insulin receptor (IR) mRNA levels and IR tyrosine kinase activity in normal myometrium and leiomyoma.
Design
Experimental study.
Setting
Academic research center.
Patients
Five women with leiomyoma submitted to hysterectomy.
Intervention
Plasma membrane fraction of human myometrium and leiomyoma were prepared and samples were incubated with and without insulin. mRNA was isolated and RT-PCR with specific primers was performed.
Main outcome measure
Western blots of plasma membranes incubated with and without insulin were performed. Chemoluminescent methods followed by densitometry were used to assess IR autophosphorylation. RT-PCR with specific primers for IR gene sequences was used to determine IR mRNA levels.
Results
IR mRNA levels in myometrium (0.634±0.038) and in leiomyoma (0.649±0.047; p=0.813) were not different. The degree of insulin-stimulated IR autophosphorylation (relative optical density of the 95 kDa band) was also not different between myometrium (1.496±0.310) and leiomyoma (1.593±0.129; p=0.650).
Conclusions
There was no difference in IR receptor expression and IR autophosphorylation between normal myometrium and leiomyoma. Other steps of insulin signaling chain may participate in the altered proliferation of leiomyomas.
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References
Capp E, Brandelli A, Monego H, Ribeiro MF, de Freitas MS, Pureur R, Tortorela H (1996) Binding and tyrosine kinase activity of insulin receptor in human normal and neoplastic endometrium. Med Sci Res 24:621–623
Chandrasekhar Y, Heiner J, Osuamkpe C, Nagamani M (1992) Insulin-like growth factor I and II binding in human myometrium and leiomyomas. Am J Obstet Gynecol 166:64–69
Cheatham B, Kahn CR (1995) Insulin action and the insulin signaling network. Endocr Rev 16:117–142
Corleta HE, Capp E, Corleta OC (1996) Insulin receptor tyrosine kinase activity in colon carcinoma. Braz J Med Biol Res 29:1593–1597
De Leo V, la Marca A, Morgante G, Severi FM, Petraglia F (2001) Administration of somatostatin analogue reduces uterine and myoma volume in women with uterine leiomyomata. Fertil Steril 75:632–633
Dupont J, LeRoith D (2001) Insulin and insulin-like growth factor I receptors: similarities and differences in signal transduction. Horm Res 55 [Suppl 2]:22–26
Englund K, Lindblom B, Carlstrom K, Gustavsson I, Sjoblom P, Blanck A (2000) Gene expression and tissue concentrations of IGF-I in human myometrium and fibroids under different hormonal conditions. Mol Hum Reprod 6:915–920
Fayed YM, Tsibris JC, Langenberg PW, Robertson AL (1989) Human uterine leiomyoma cells: binding and growth responses to epidermal growth factor, platelet-derived growth factor, and insulin. Lab Invest 60:30–37
Giudice LC, Irwin JC, Dsupin BA, Pannier EM, Jin IH, Vu TH (1993) Insulin-like growth factor (IGF), IGF binding protein (IGFBP), and IGF receptor gene expression and IGFBP synthesis in human uterine leiomyomata. Hum Reprod 8:1796–1806
Harrison-Woolrych ML, Charnock-Jones DS, Smith SK (1994) Quantification of messenger ribonucleic acid for epidermal growth factor in human myometrium and leiomyomata using reverse transcriptase polymerase chain reaction. J Clin Endocrinol Metab 78:1179–1184
Kellerer M, von Eye Corleta H, Muhlhofer A, Capp E, Mosthaf L, Bock S et al (1995) Insulin- and insulin-like growth-factor-I receptor tyrosine-kinase activities in human renal carcinoma. Int J Cancer 62:501–507
Kurachi O, Matsuo H, Samoto T, Maruo T (2001) Tumor necrosis factor-alpha expression in human uterine leiomyoma and its down-regulation by progesterone. J Clin Endocrinol Metab 86:2275–2280
Liu HC, He ZY, Tang YX (1997) Simultaneous detection of multiple gene expression in mouse and human individual preimplantation embryos. Fertil Steril 67:733–741
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with folic phenol reagent. J Biol Chem 193:265–275
Maruo T, Matsuo H, Samoto T, Shimomura Y, Kurachi O, Gao Z et al (2001) Effects of progesterone on uterine leiomyoma growth and apoptosis. Steroids 65:585–592
Moran C, Huerta R, Conway-Myers BA, Hines GA, Azziz R (2001) Altered autophosphorylation of the insulin receptor in the ovary of a woman with polycystic ovary syndrome. Fertil Steril 75:625–628
Nagamani M, Stuart CA (1992) Specific binding sites for insulin in the human myometrium and leiomyomas of the uterus. Fertil Steril 58:120–123
Pandini G, Vigneri R, Costantino A, Frasca F, Ippolito A, Fujita-Yamaguchi Y et al (1999) Insulin and insulin-like growth factor-I (IGF-I) receptor overexpression in breast cancers leads to insulin/IGF-I hybrid receptor overexpression: evidence for a second mechanism of IGF-I signaling. Clin Cancer Res 5:1935–1944
Sale EM, Atkinson PP, Arnott CH, Chad JE, Sale GJ (1999) Role of ERK1/ERK2 and p70S6 K pathway in insulin signalling of protein synthesis. FEBS Lett 446:122–126
Seedorf K (1995) Intracellular signaling by growth factors. Metabolism 44:24–32
Silva IS, Morsch DM, Urnauer L, Spritzer PM (2001) Androgen-induced cell growth and c-myc expression in human non-transformed epithelial prostatic cells in primary culture. Endocr Res 27:153–169
Stewart EA (2001) Uterine fibroids. Lancet 357:293–298
Taplin ME, Bubley GJ, Shuster TD, Frantz ME, Spooner AE, Ogata GK et al (1995) Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. N Engl J Med 332:1393–1398
Vollenhoven BJ, Herington AC, Healy DL (1995) Epidermal growth factor and transforming growth factor-beta in uterine fibroids and myometrium. Gynecol Obstet Invest 40:120–124
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Financial support: FAPERGS, FIPE/HCPA, PROPESQ/UFRGS.
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Toscani, G.K., Chaves, E.M., Cervi, F.L. et al. Gene expression and tyrosine kinase activity of insulin receptor in uterine leiomyoma and matched myometrium. Arch Gynecol Obstet 270, 170–173 (2004). https://doi.org/10.1007/s00404-003-0534-5
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DOI: https://doi.org/10.1007/s00404-003-0534-5