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Expression of both oestrogen receptor alpha and beta in human skeletal muscle tissue

  • A. WiikEmail author
  • M. Ekman
  • O. Johansson
  • E. Jansson
  • M. Esbjörnsson
Original Paper

Abstract

There are two oestrogen receptors (ERs), ERα and ERβ. ERβ protein is expressed in human skeletal muscle in the nuclei of both myofibres and endothelial cells, whether ERα protein is present in this tissue is unknown. We studied the expression of ERα protein in human skeletal muscle biopsies taken from vastus lateralis from four men, four women, two children and two postmenopausal women. Immunohistochemistry was used to determine the proportions of nuclei that were positively stained for ERα, the proportion of ERα-positive nuclei located in the muscle fibres and in capillaries and to test for possible co-expression of ERα and ERβ. Both ERs were expressed in all subjects. Of all nuclei, 63% stained for ERα with no sex difference. ERα was localised both in myofibres and in endothelial cells of the capillaries, 25% of the ERα-positive nuclei were located in the capillaries. ERα and ERβ were generally expressed in the same nuclei. The present study shows for the first time the expression of ERα protein in human skeletal muscle independently of age and sex. These results might improve understanding of the physiological role of oestrogen in human skeletal muscle and raise new questions about activation of ERs in skeletal muscle.

Keywords

Age Capillaries Collagen IV Immunohistochemistry Sex 

Notes

Acknowledgments

This study was supported by grants from the Swedish National Centre for Research in Sports, Swedish Research Council (14295), Centre for Gender Medicine, Åke Wibergs Stiftelse, Magnus Bergvalls Stiftelse, Stiftelsen Tornspiran and The Cancer and Allergy Foundation (Cancer- och Allergifonden). The authors wish to acknowledge Associate Professor Margaret Warner for providing the ERβ 503 antibody. We also express our gratitude to Dr Monica Dahlström and Emeritus Professor Lennart Kaijser for their work in the study on children and to Professor Britth-Marie Landgren for her involvement in the project with postmenopausal women.

References

  1. Arsic N, Zacchigna S, Zentilin L, Ramirez-Correa G, Pattarini L, Salvi A, Sinagra G, Giacca M (2004) Vascular endothelial growth factor stimulates skeletal muscle regeneration in vivo. Mol Ther 10:844–854PubMedCrossRefGoogle Scholar
  2. Barros RP, Machado UF, Warner M, Gustafsson JA (2006) Muscle GLUT4 regulation by estrogen receptors ERbeta and ERalpha. Proc Natl Acad Sci USA 103:1605–1608PubMedCrossRefGoogle Scholar
  3. Batra GS, Hainey L, Freemont AJ, Andrew G, Saunders PT, Hoyland JA, Braidman IP (2003) Evidence for cell-specific changes with age in expression of oestrogen receptor (ER) alpha and beta in bone fractures from men and women. J Pathol 200:65–73PubMedCrossRefGoogle Scholar
  4. Bergström J (1962) Muscle electrolytes in man. Scan J Clin Lab Invest 14:1–110CrossRefGoogle Scholar
  5. Bunone G, Briand PA, Miksicek RJ, Picard D (1996) Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation. Embo J 15:2174–2183PubMedGoogle Scholar
  6. Burleigh I (1980) Growth curves in muscle nucleic acid and protein: problems of interpretation at the level of the muscle cell. In: Lawrence T (ed) Growth in animals. Butterworths, London, pp 101–136Google Scholar
  7. Cenni B, Picard D (1999) Ligand-independent activation of steroid receptors: new roles for old players. Trends Endocrinol Metab 10:41–46PubMedCrossRefGoogle Scholar
  8. Ciana P, Raviscioni M, Mussi P, Vegeto E, Que I, Parker MG, Lowik C, Maggi A (2003) In vivo imaging of transcriptionally active estrogen receptors. Nat Med 9:82–86PubMedCrossRefGoogle Scholar
  9. Cowley SM, Hoare S, Mosselman S, Parker MG (1997) Estrogen receptors alpha and beta form heterodimers on DNA. J Biol Chem 272:19858–19862PubMedCrossRefGoogle Scholar
  10. Cutolo M, Sulli A, Seriolo B, Accardo S, Masi AT (1995) Estrogens, the immune response and autoimmunity. Clin Exp Rheumatol 13:217–226PubMedGoogle Scholar
  11. Frandsen U, Lopez-Figueroa M, Hellsten Y (1996) Localization of nitric oxide synthase in human skeletal muscle. Biochem Biophys Res Commun 227:88–93PubMedCrossRefGoogle Scholar
  12. Gargett CE, Bucak K, Zaitseva M, Chu S, Taylor N, Fuller PJ, Rogers PA (2002) Estrogen receptor-alpha and -beta expression in microvascular endothelial cells and smooth muscle cells of myometrium and leiomyoma. Mol Hum Reprod 8:770–775PubMedCrossRefGoogle Scholar
  13. Greeves JP, Cable NT, Luckas MJ, Reilly T, Biljan MM (1997) Effects of acute changes in oestrogen on muscle function of the first dorsal interosseus muscle in humans. J Physiol 500(Pt 1):265–270PubMedGoogle Scholar
  14. Gustafsson T, Kraus WE (2001) Exercise-induced angiogenesis-related growth and transcription factors in skeletal muscle, and their modification in muscle pathology. Front Biosci 6:D75–D89PubMedCrossRefGoogle Scholar
  15. Gustafsson T, Puntschart A, Kaijser L, Jansson E, Sundberg CJ (1999) Exercise-induced expression of angiogenesis-related transcription and growth factors in human skeletal muscle. Am J Physiol 276:H679–H685PubMedGoogle Scholar
  16. Hall JM, McDonnell DP (1999) The estrogen receptor beta-isoform (ERbeta) of the human estrogen receptor modulates ERalpha transcriptional activity and is a key regulator of the cellular response to estrogens and antiestrogens. Endocrinology 140:5566–5578PubMedCrossRefGoogle Scholar
  17. Helguero LA, Faulds MH, Gustafsson JA, Haldosen LA (2005) Estrogen receptors alfa (ERalpha) and beta (ERbeta) differentially regulate proliferation and apoptosis of the normal murine mammary epithelial cell line HC11. Oncogene 24:6605–6616PubMedCrossRefGoogle Scholar
  18. Hyder SM, Nawaz Z, Chiappetta C, Stancel GM (2000) Identification of functional estrogen response elements in the gene coding for the potent angiogenic factor vascular endothelial growth factor. Cancer Res 60:3183–3190PubMedGoogle Scholar
  19. Ishunina TA, Kruijver FP, Balesar R, Swaab DF (2000) Differential expression of estrogen receptor alpha and beta immunoreactivity in the human supraoptic nucleus in relation to sex and aging. J Clin Endocrinol Metab 85:3283–3291PubMedCrossRefGoogle Scholar
  20. Kadi F, Charifi N, Denis C, Lexell J, Andersen JL, Schjerling P, Olsen S, Kjaer M (2005) The behaviour of satellite cells in response to exercise: what have we learned from human studies? Pflugers Arch 451:319–327PubMedCrossRefGoogle Scholar
  21. Kalbe C, Mau M, Wollenhaupt K, Rehfeldt C (2007) Evidence for estrogen receptor alpha and beta expression in skeletal muscle of pigs. Histochem Cell Biol 127:95–107PubMedCrossRefGoogle Scholar
  22. Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H, Masushige S, Gotoh Y, Nishida E, Kawashima H, Metzger D, Chambon P (1995) Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science 270:1491–1494PubMedCrossRefGoogle Scholar
  23. Kim-Schulze S, McGowan KA, Hubchak SC, Cid MC, Martin MB, Kleinman HK, Greene GL, Schnaper HW (1996) Expression of an estrogen receptor by human coronary artery and umbilical vein endothelial cells. Circulation 94:1402–1407PubMedGoogle Scholar
  24. Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA (1996) Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 93:5925–5930PubMedCrossRefGoogle Scholar
  25. Lemoine S, Granier P, Tiffoche C, Rannou-Bekono F, Thieulant ML, Delamarche P (2003) Estrogen receptor alpha mRNA in human skeletal muscles. Med Sci Sports Exerc 35:439–443PubMedCrossRefGoogle Scholar
  26. Malm C, Nyberg P, Engstrom M, Sjodin B, Lenkei R, Ekblom B, Lundberg I (2000) Immunological changes in human skeletal muscle and blood after eccentric exercise and multiple biopsies. J Physiol 529(Pt 1):243–262PubMedCrossRefGoogle Scholar
  27. Manolagas SC, Kousteni S (2001) Perspective: nonreproductive sites of action of reproductive hormones. Endocrinology 142:2200–2204PubMedCrossRefGoogle Scholar
  28. Mueller MD, Vigne JL, Minchenko A, Lebovic DI, Leitman DC, Taylor RN (2000) Regulation of vascular endothelial growth factor (VEGF) gene transcription by estrogen receptors alpha and beta. Proc Natl Acad Sci USA 97:10972–10977PubMedCrossRefGoogle Scholar
  29. Murphy LJ, Ghahary A (1990) Uterine insulin-like growth factor-1: regulation of expression and its role in estrogen-induced uterine proliferation. Endocr Rev 11:443–453PubMedGoogle Scholar
  30. Pettersson K, Grandien K, Kuiper GG, Gustafsson JA (1997) Mouse estrogen receptor beta forms estrogen response element-binding heterodimers with estrogen receptor alpha. Mol Endocrinol 11:1486–1496PubMedCrossRefGoogle Scholar
  31. Pettersson K, Delaunay F, Gustafsson JA (2000) Estrogen receptor beta acts as a dominant regulator of estrogen signaling. Oncogene 19:4970–4978PubMedCrossRefGoogle Scholar
  32. Porter MM, Stuart S, Boij M, Lexell J (2002) Capillary supply of the tibialis anterior muscle in young, healthy, and moderately active men and women. J Appl Physiol 92:1451–1457PubMedGoogle Scholar
  33. Saji S, Jensen EV, Nilsson S, Rylander T, Warner M, Gustafsson JA (2000) Estrogen receptors alpha and beta in the rodent mammary gland. Proc Natl Acad Sci USA 97:337–342PubMedCrossRefGoogle Scholar
  34. Sarwar R, Niclos BB, Rutherford OM (1996) Changes in muscle strength, relaxation rate and fatiguability during the human menstrual cycle. J Physiol 493(Pt 1):267–272PubMedGoogle Scholar
  35. Saville B, Wormke M, Wang F, Nguyen T, Enmark E, Kuiper G, Gustafsson JA, Safe S (2000) Ligand-, cell-, and estrogen receptor subtype (alpha/beta)-dependent activation at GC-rich (Sp1) promoter elements. J Biol Chem 275:5379–5387PubMedCrossRefGoogle Scholar
  36. Skelton DA, Phillips SK, Bruce SA, Naylor CH, Woledge RC (1999) Hormone replacement therapy increases isometric muscle strength of adductor pollicis in post-menopausal women. Clin Sci (Lond) 96:357–364CrossRefGoogle Scholar
  37. Steensberg A, Keller C, Hillig T, Frosig C, Wojtaszewski JF, Pedersen BK, Pilegaard H, Sander M (2007) Nitric oxide production is a proximal signaling event controlling exercise-induced mRNA expression in human skeletal muscle. Faseb J 21:2683–2694PubMedCrossRefGoogle Scholar
  38. Taylor AH, Al-Azzawi F (2000) Immunolocalisation of oestrogen receptor beta in human tissues. J Mol Endocrinol 24:145–155PubMedCrossRefGoogle Scholar
  39. Tremblay A, Tremblay GB, Labrie F, Giguere V (1999) Ligand-independent recruitment of SRC-1 to estrogen receptor beta through phosphorylation of activation function AF-1. Mol Cell 3:513–519PubMedCrossRefGoogle Scholar
  40. Weiner CP, Lizasoain I, Baylis SA, Knowles RG, Charles IG, Moncada S (1994) Induction of calcium-dependent nitric oxide synthases by sex hormones. Proc Natl Acad Sci USA 91:5212–5216PubMedCrossRefGoogle Scholar
  41. Wiik A, Glenmark B, Ekman M, Esbjornsson-Liljedahl M, Johansson O, Bodin K, Enmark E, Jansson E (2003) Oestrogen receptor beta is expressed in adult human skeletal muscle both at the mRNA and protein level. Acta Physiol Scand 179:381–387PubMedCrossRefGoogle Scholar
  42. Wiik A, Ekman M, Morgan G, Johansson O, Jansson E, Esbjornsson M (2005) Oestrogen receptor beta is present in both muscle fibres and endothelial cells within human skeletal muscle tissue. Histochem Cell Biol 124:161–165PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • A. Wiik
    • 1
    Email author
  • M. Ekman
    • 2
  • O. Johansson
    • 2
  • E. Jansson
    • 1
  • M. Esbjörnsson
    • 1
  1. 1.Department of Laboratory Medicine, Division of Clinical PhysiologyKarolinska Institutet, Karolinska University Hospital HuddingeStockholmSweden
  2. 2.Department of Neuroscience, The Experimental Dermatology Unit Karolinska InstitutetStockholmSweden

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