Article Data

  • Views 195
  • Dowloads 109

Original Research

Open Access

Further studies on leptin and leptin receptor expression in myometrium and uterine myomas

  • A. Markowska1,*,
  • M. Rucinski2
  • K. Drews1
  • L.K. Malendowicz2

1Department of Perinatology and Gynecology, Poland

2Department of Histology and Embryology, Poznan University of Medical Sciences, Poznan, Poland

DOI: 10.12892/ejgo200505517 Vol.26,Issue 5,September 2005 pp.517-525

Published: 10 September 2005

*Corresponding Author(s): A. Markowska E-mail:

Abstract

Aim: Examination of the potential role of leptin in the development of uterine myomas. Expression of the leptin gene and leptin receptor gene was tested in the myometrium of healthy women, and in myomas and the surrounding myometrium of women with benign tumors.

Methods: Using RT-PCR, expression of the leptin gene and leptin receptor gene were studied in myomas and in the surrounding myometrium in 30 women with uterine myomas at various phases of the menstrual cycle, and in the myometrium of ten women in a control group. Presence of leptin gene proteins and leptin receptor gene proteins in the women was also examined by Western blotting.

Results: Using RT-PCR, expression of the leptin gene was demonstrated both in myomas and in the surrounding myometrium. In contrast, expression of the gene could not be detected in the myometrium of healthy women. The results were confirmed by Western blotting, which documented the identical distribution of leptin proteins and leptin receptor proteins in studied tissues.

Conclusion: Demonstration of the expression of leptin genes and leptin proteins in uterine myomas and in the surrounding myometrium, and their absence in the myometrium of healthy women suggests the involvement of leptin in the development of uterine myomas.

Keywords

Leptin; Leptin receptor; Uterine myoma

Cite and Share

A. Markowska,M. Rucinski,K. Drews,L.K. Malendowicz. Further studies on leptin and leptin receptor expression in myometrium and uterine myomas. European Journal of Gynaecological Oncology. 2005. 26(5);517-525.

References

[1] Goumenou A.G., Matalliotakis I.M., Koumantakis G.E., Panidis D.K.: "The role of leptin in fertility". Eur J. Obstet. Gynecol Reprod. Biol., 2003, 106, 118.

[2] Ramos M.P., Rueda B.R., Leavis P.C., Gonzalez R.R.: "Leptin serves as an upstream activator of an obligatory signaling cascade in the embryo-implantation process". Endocrinology, 2005, 146, 694.

[3] Chan, T.-F., Su, J.-H., Chung, Y.-F., Chang, H.L., Yuan, S.-S.F "Deacreased serum leptin levels in women with uterine leiomyomas". Acta Obster. Gynecol. Scand., 2003, 82, 173.

[4] Mantzoros Ch.S.: "The role of leptin in human obesity and disease. "A review of current evidence". Ann. Intern. Med., 1999, 130, 671.

[5] Somasundar P., McFadden D.W., Hileman S.M., Vona-Davis L.: "Leptin is a growth factor in cancer". J. Surg. Res., 2004, 116, 337.

[6] Bajari T.M., Strasser V., Nimpf J., Schneider VJ.: "A model for modulation of leptin activity by association with clusterin." FASEB, 2003, 17, 1505.

[7] Oda A., Taniguchi T., Yokoyama M.: "Leptin stimulates aortic smooth muscle cell proliferation and migration". Kobe J. Med. Sci., 2001, 47, 141.

[8] Bjorbaek C., Uotani S., da-Silva B., Filer J.S.: "Divergent signaling capacities of the long and short isoforms of the leptin receptor". J. Biol. Chem., 1997, 272, 32686.

[9] Ishida-Takahashi R., Uotani S., Abe T., Degawa-Yamauchi M., Fukushima T., Fujita N. et al.: "Rapid inh伽tion of leptin signaling by glucocorticoids in vitro and in vivo". J. Biol. Chem., 2004, 279, 19658.

[10] Ihle J.N.: "STATs: signal transducers and activators of transcnption". Cell, 1996, 84, 331.

[11] Considine R.V., Sinha M.K., Heiman M.L., Kriavnunas A., Stephens T.W., Nyce M.R. et al.: "Serum irnmunoreactive-leptin concentration in normal-weight and obese humans". N. Engl. J. Med., 1996, 334, 292.

[12] Caro J.F., Kolaczynski J.V., Nyce M.R., Ohannesian J.P., Opentanova J., Goldman W.H.: "Decreased cerebrospinal-fluid serum leptin ratio in obesity: a possible mechanism for leptin resistance". Lancet, 1996, 348, 159.

[13] Corsonello A., Petricone F., Malara A., De-Domenico D., Loddo S., Bueni M. et al.: "Leptin dependent platelet aggregation in healthy overweight and obese subjects". Int. J. Obes. Re/at. Metab. Disord., 2003, 27, 566.

[14] Seufert J.: "Leptin effects on pancreatic B cell gene expression and function". Diabetes, 2004, 53 (supp. 1), 152.

[15] Finck B.N., Johnson R.W.: "Tumor necrosis factor-8 regulates secretion of the adipocyte-derived cytokine, leptin". Microsc. Res Tech., 2000, 50, 209.

[16] Liao S.C., Lee M.B., Lee Y.J., Huang T.S.: "Hyperleptinemia in subjects with perisistent partial postraumatic stress disorder after a major eacthquake". Psychosom. Med., 2004, 66, 23.

[17] Savoia C., Schiffrin E.L.: "Significance of recently identified peptides in hypertension: endothelin, natriuretic peptides, adrenomedullin, leptin". Med. Clin. N. Am., 2004, 88, 39.

[18] Najib S., Sanchez-Margalet V.: "Human leptin promotes survival of human circulating blood monocytes prone to apoptosis by activation of p 42/44 MAPK pathway". Cell. Immunol., 2002, 220, 143.

[19] Mazziotti G., Parkes A.B., Lage M., Premawardhana L.D.K.E., Casanueva F.F., Lazarus J.H.: "High leptin levels in women developing postpartum thyroiditis". Clin. Endocrinol., 2004, 60, 208.

[20] Ruhl C.E., Everhart J.E., Ding J., Goodpaster B.H., Kanaya A.M., Simonsick E.M. et al.: "Serum leptin concentrations and body adipocyte measures in older black and white adults". Am. J. Clin. Nutr., 2004, 80, 576.

[21] Halaas J.L., Friedman J.M.: "Obesity and the adipocyte. Leptin and its receptor". J. Endocrinol., 1997, 155, 215.

[22] Perry H.M., Morley J.E., Horowitz M., Kaiser F.E., Miller D.K., Wittert G.: "Body composition and age in African-American and Caucasian women. Relationship to plasma leptin levels". Metabolism, 1997, 12, 1399.

[23]Zimmet P., Hodge A., Nicolson M., Staten M., de Courten M., Moore J. et al.: "Serum leptin concentration, obesity and insulin resistance in Western Samoans: cross sectional study". Br. Med. J., 1996, 313, 965.

[24] Saad M.F., Damani S., Gingerich R.L., Riad-Gabryel M.G., Khan A., Boyadjian R. et al.: "Sexual dimorphism in plasma leptin concentration". J. Clin. Endocrinol. Metab., 1997, 82, 579.

[25] Shimokata H., Tobin J.D., Muller D.C., Elahi D., Coon J., Andres R.: "Studies in the distribution of body fat: I Effects of age, sex, and obesity". J. Gerontology, 1989, 44, M66.

[26] Paolisso G., Rizzo M.R., Mazziotti G., Rotondi M., Tagliamonte M.R., Verricchio G. et al.: "Lack of association between changes in plasma leptin concentration and foot intake during the menstrual cycle". Eur. J. Clin. Invest., 1999, 29, 490.

[27] Hardie L., Trayhurn P., Abramovich D., Fowler P.: "Circulatmg leptin in women: a longitudinal study in the menstrual cycle and during pregnancy". Clin. Endocrinol., 1997, 47, 101.

[28] Mills P.J., Ziegler M.G., Morrison T.A.: "Leptin is related to epinephrine levels but not reproductive hormone levels in cycling African-American and Caucasian women". Life Sci., 1998, 63, 617.

[29] Nowicki A., Adamkiewicz G., Brye W., Kokot F.: "The influence of luteinizing hormone-releasing hormone analog on serum leptin and body composition in women with solitary uterine myoma". Am. J. Obstet Gynecol., 2002, 186, 340.

[30] Zawadzka M., Kaminska B.: "Immun9supressant FK 505 affects multiple signalling pathways and modulates gene expression in astrocytes". Mo/. Cell. Neurosci., 2003, 22, 202.

[31] Duerenberg P., Weststrate J.A., Seidell J.C.: "Body mass index as a measure of body fatness: age-and sex-specific prediction formulas". Br. J. Nutr., 1991, 65, 105.

[32] Kitawaki J., Koshiba H., Ishihara H., Kusuki I., Tsukamoto K., Honjo H.: "Expression of leptin receptor in human endometrium and fluctuation during the menstrual cycle". J. Clin. Endocrinol. Metab., 2000, 85, 1946.

[33] Alfer J., Muller-Schottle F., Classen-Linke I. von Rango V., Happel L., Beier-Hellwig K. et al.: "The endometrium as a novel target for leptin: differences in fertility and subfertility". Mol Hum. Reprod., 2000, 6, 595.

[34] Lima-Couy J., Cervero A., Bonilla-Musoles F., Pellicer A., Simon C.: "Endometrial leptin and leptin receptor expression in women with severe/moderate endometriosis". Mo!. Hum. Reprod., 2004, 10, 777.

[35] Wu M.H., Chuang P.Ch., Chen H.M., Lin Ch., T sai S.J "Increased leptin expression in endometriosis cell is associated with endometrial stromal cell proliferation and leptin gene up-regulation". Mol. Hum. Reprod., 2002, 8, 456.

[36] Quinton N.D., Laird S.M., Tuckerman E.M., Cork B.A., Blakemore A.I.F.: "Expression of leptin receptor isoforms in vitro: Lack of effects of leptin on endometrial cytokine and MMP production". Am. J., 2003, 50, 224.

[37] Markowska A., Belloni A., Nussdorfer G.G., Rucinski M., Drews K., Malendowicz L.K.: "Leptin and leptin receptor genes and proteins in myometrium and uterine myomas: is leptin involved in tumor development?". Int. J. Oneal., 2005, in press.

[38] Mix H., W呴aja A., Jandl 0., Cornberg M., Kaul A., Goke M. et al.: "Expression of leptin and leptin receptor isoforms in the human stomach". Gut, 2000, 47 (4), 481.

[39] Teirmaa T., Luukkaa V., Rouru J., Koulu M., Huupponen R.: "Correlation between circulating leptin and luteinizing hormone during the menstrual cycle in normal - weight women". Eur. J. Endocrinol., 1998, 139, 190.

[40] Boden G., Chen X., Kolaczynski J.W., Polansky M.: "Effects of prolonged hyperinsulinemia on serum leptin in normal human subjects". J. Clin. Invest., 1997, 100, 1107.

[41] Bouloumie A., Drexler H.C., Lafontan M., Busse R.: "Leptin the product of Ob gene, promotes angiogenesis". Circ. Res., 1998, 83, 1059.

[42] Ahima R.S., Osei S.Y.: "Leptin signaling". Physiol. Behav., 2004, 81, 223.

[43] Ahima R.S., Saper C.B., F lier J.S., Elmquist J.K.: "Leptin regulation of neuroendocrine system". Front. Neuroendocrinology, 2000, 21, 263.

[44] Leee G.H., Proenca R., Montez J.M., Carroll K.M., Dervishzadeh J.G., Lee J., F riedman J.M.: "Abnormal splicing of the leptin receptor in diabetic mice". Nature, 1996, 379, 632.

[45] Wang M.Y., Zhou Y.T., Newgard Ch.B., Unger R.H.: "A novelleptin receptor isoform in rat". FESS Lett., 1996, 392, 87.

[46] Karlsson C., Lindell K., Svensson E., Bergh Ch., Lind P., Billig H et al.: "Expression of functional leptin receptors in human ovary" J. Clin. Endocrinol. Metab., 1997, 82, 4144.

[47] Geisthi:ivel F., Jochmann N., Widjaja A., Horn R., Brabant S "Serum pattern of circulating free leptin bound leptin and solube leptin receptor in the physiological menstrual cycle". Fertil Steril., 2004, 81, 398.

[48] Bornstein S.R., Licinio J., Tauchnitz R., Engelmann L., Negrao A.B., Gold P., Chrousos G.P.: "Leptin levels are increased in survivors of acute sepsis associated loss of diurnal rhythm in cortisol and leptin secretion". J. Clin. Endocrinol. Metab., 1998, 83, 280.

[49] Vollenhoven BJ., Lawrence A.S. Healy D.L.: "Uterine fibroids: a clinical review". Br. J. Obstet. Gynaecol., 1990, 97, 285.

[50] Cioffi J.A., Shafer A.W., Zupancic T.J., Smith-Gbur J., Mikhail A., Platika D., Snodgrass H.R.: "Novel B219/0B receptor isoforms: Possible role of leptin in hematopoesis and reproduction". Nature, 1996, 2, 585.

[51] Tartaglia L.A., Dembski M., Weng X., Deng N., Culpepper J., Devos R. et al.: "Identificiation and expression cloning of a leptin receptor, OB-R". Cell, 1995, 83, 1263.

[52] Parazzini F., Negri E.,LaVecchia C.: "Uterine myomas and smokmg: result from an Italian study". J. Reprod. Med., 1966, 41, 316.

[53] Stewart E.A.: "Uterine fibroids". Lancet, 2001, 357, 293.

[54] Wilson E.A., Yang F., Rees E.D.: "Estradiol and progesterone binding in uterine leiomyomata and normal uterine tissues". Obstet. Gynecol., 1980, 55, 20.

[55] Rein M.S., Barbieri R.L., Friedman A.J.: "Progesterone: a critical role in the pathogenesis of uterine myomas". Am. J. Obstet. Gynecol., 1995, 172, 14.

[56] Dawood M.Y., Khan Dawood F.S.: "Plasma insulin-like growth factor-I, CA 125, estrogen and progesterone in women with leiomyomas". Fertil. Steril., 1994, 61, 617.

[57] Baumgartner R.N., Waters D.L., Morley J.E., Patrick P., Montoya G.D., Garry P.J.: "Age-related changes in sex hormones affect the sex difference in serum leptin independently of changes in body fat". Metabolism, 1999, 48, 378.

[58] Matal\iotakis I.M., Koumantaki Y.G., Neonaki M.A., Goumenou A.G., Koumantakis G.E., Kyriakou D.S., Koumantakis E.E "Increase in serum leptin concentrations among women with endometriosis during danazol and leuprolide depot treatments". Am. J. Obstet. Gynecol., 2000, 183, 58.

[59] Gonzalez R.R., Caballero-Campo P., Jasper M., Mercader A., Devoto L., Pellicer A., Simon L.: "Leptin and leptin receptor are expressed in the human endometrium and endometrial leptin secretion is regulated by the human blastocyst". J. Clin. Endocrinol. Metab., 2000, 85, 4883.

[60] Sato F., Nishi M., Kudo R., Miyake H.: "Body fat distribution and uterine leiomyomas". J. Epidemiol., 1998, 8, 176.

[61] Cervera A., Horcajadas J.A., Martin J., Pellicer A., Simon C "The leptin system during human endometrial respectivity and preimplantation development". J. Clin. Endocrinol. Metab., 2004, 89, 2442.

[62] Brossart P., Keilholz U., Scheibenbongen C., Mohler T., Willhauck M., Hunstein W. et al.: " Detection of residual tumor cells in patients with malignant melanoma responding to immunotherapy". J. lmmun,other., 1994, 15, 38.

[63] Isse N., Ogawa Y., Tamura N., Masuzaki H., Mori K., Okazaki T. et al.: "Structural organization and chromosomal assignment of the human obese gene". J. Biol. Chem., 1995, 46, 27728.

[64] Chung W.K., Power-Kehoe L., Chua M., Lee R., Leibel R.L.: "Genomic structure of the human OB receptor and identification of two novel intronic microsatellites". Genome Res., 1996, 12, 1192.

[65] Bennet B.D., Solar G.P., Yuan J.Q., Mathias J., T homas Gr., Matthews W.: "A role of leptin and its cognate receptor in hematopoesis". Cur. Biol., 1996, 6, 1170.

[66] Mix H., Widjaja A., Jandl O., Cornberg M., Kaul A., Goke M., Beil W., Kuske M., Brabant G., Manns M.P., Wagner S.: "Expression of leptin and leptin receptor isoforms in the human stomach". Gut, 2000, 47, 481.

[67] Cioffi J.A., Shafer A.W., Zupancic T.J., Smith-Gbur J., Mikhail A., Platika D. et al.: "Novel B219/0B. Receptor isoforms: Possible role of leptin in hematopoesis and reproduction". Nature Med., 1996, 2, 585.

[68] Lambrinoudaki I.V., Christodoulakos G.E., Panoulis C.P., Rizos D.A., Dendrinos S.G., Liakakos T. et al.: "Effect of hormone replacement therapy and tibolone on serum leptin levels in postmenopausal women". Maturitas, 2004, 48, 107.

[69] Dominguez F., Pellicer A., Simon C.: "Paracrine dialogue m implantation". Mol. Cell Endocrinol., 2002, 186, 175.

[70] Koshiba H., Kitawaki J., Ishihara H., Kado N., Kusuki I., Tsukamoto K., Honjo H.: "Progesterone inhibition of functional leptin receptor mRNA expression in human endometrium". Mol. Hum. Reprod., 2001, 7, 567.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.

Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.

JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Submission Turnaround Time

Conferences

Top