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Endocrine

, Volume 41, Issue 2, pp 256–265 | Cite as

An ontogenic study of adrenomedullin gene expression in the rat lung, adrenal, kidney, and heart

  • P. F. Wong
  • W. S. O
  • F. TangEmail author
Original Article

Abstract

In this study, the gene expression of adrenomedullin (Adm) in the peripheral tissues which include lung, adrenal, kidney, and heart during development was investigated in the rat. The preproadrenomedullin (preproAdm) mRNA and mRNAs of its related receptor components, calcitonin receptor-like receptor (Crlr), and receptor activity-modifying proteins (Ramp1, 2 and 3) of the lung, adrenal, kidney, and heart were measured by real-time RT-PCR and the ADM peptide measured by radioimmunoassay in 1-, 7-, 21-day-old rats and the adult rats. From day 1 to 21, preproAdm mRNA levels increased with age in the lung, the kidney, and the heart but decreased with age in the adrenal. ADM levels, however, increased with age in the lung but decreased with age in the kidney, the adrenal, and the heart. The preproAdm levels in the lung, in the kidney, and in the adrenal all increased in the adult rat. ADM peptide levels, however, decreased in the adult rat. Crlr and Ramp2 gene expression increased with age in the lung, in the kidney, and in the heart but decreased with age in the adrenal in the prepubertal rats. The results indicate that the levels of preproAdm mRNA, ADM peptide and its receptor component mRNAs in different tissues followed different patterns of changes during development.

Keywords

Ontogeny Adrenomedullin Lung Adrenal Kidney Heart 

Notes

Acknowledgments

This study was supported by a grant from the Committee o Research and Conference Grants (CRCG) of the University of Hong Kong.

References

  1. 1.
    K. Kitamura, K. Kangawa, M. Kawamoto, Y. Ichiki, S. Nakamura, H. Matsuo, T. Eto, Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem. Biophys. Res. Commun. 192, 553–560 (1993)PubMedCrossRefGoogle Scholar
  2. 2.
    K. Kitamura, J. Sakata, K. Kangawa, M. Kojima, H. Matsuo, T. Eto, Cloning and characterization of cDNA encoding a precursor for human adrenomedullin. Biochem. Biophys. Res. Commun. 194, 720–725 (1993)PubMedCrossRefGoogle Scholar
  3. 3.
    J. Sakata, T. Shimokubo, K. Kitamura, S. Nakamura, K. Kangawa, H. Matsuo, T. Eto, Molecular cloning and biological activities of rat adrenomedullin, a hypotensive peptide. Biochem. Biophys. Res. Commun. 195, 917–921 (1993)CrossRefGoogle Scholar
  4. 4.
    S.D. Brain, A.D. Grant, Vascular actions of calcitonin gene-related peptide and adrenomedullin. Physiol. Rev. 4, 903–934 (2004)CrossRefGoogle Scholar
  5. 5.
    R. Muff, W. Born, J.A. Fischer, Adrenomedullin selectivity of calcitonin-like receptor/receptor activity modifying proteins. Hypertens. Res. 26, S3–S8 (2003)PubMedCrossRefGoogle Scholar
  6. 6.
    Y. Asada, S. Hara, K. Marutsuka, K. Kitamura, T. Tsuji, J. Sakata, Y. Sato, A. Kisanuki, T. Eto, A. Sumiyoshi, Novel distribution of adrenomedullin-immunoreactive cells in human tissues. Histochem. Cell Biol. 112(3), 185–191 (1999)PubMedCrossRefGoogle Scholar
  7. 7.
    I.S. Hwang, F. Tang, The distribution and gene expression of adrenomedullin in the rat brain: peptide/mRNA and precursor/active peptide relationship. Neurosci. Lett. 267, 85–88 (1999)PubMedCrossRefGoogle Scholar
  8. 8.
    I.S. Hwang, F. Tang, Peripheral distribution and gene expression of adrenomedullin in the rat: possible source of blood adrenomedullin. Neuropeptides 34, 32–37 (2000)PubMedCrossRefGoogle Scholar
  9. 9.
    Y. Ichiki, K. Kitamura, K. Kangawa, M. Kawamoto, H. Matsuo, T. Eto, Distribution and characterization of immunoreactive adrenomedullin in porcine tissue, and isolation of adrenomedullin [26–52] and adrenomedullin [34–52] from porcine duodenum. J. Biochem. 118(4), 765–770 (1995)PubMedGoogle Scholar
  10. 10.
    F. Satoh, K. Takahashi, O. Murakami, K. Totsune, M. Sone, M. Ohneda, H. Sasano, T. Mouri, Immunocytochemical localization of adrenomedullin-like immunoreactivity in the human hypothalamus and the adrenal gland. Neurosci. Lett. 203(3), 207–210 (1996)PubMedCrossRefGoogle Scholar
  11. 11.
    N. Minamino, K. Kikumoto, Y. Isumi. Regulation of adrenomedullin expression and release. Microsc. Res. Tech. 57(1), 28–39 Review (2002)Google Scholar
  12. 12.
    J.R. Cockcroft, J.P. Noon, J. Gardner-Medwin, T. Bennett, Haemodynamic effects of adrenomedullin in human resistance and capacitance vessels. Br. J. Clin. Pharmacol. 44(1), 57–60 (1997)PubMedCrossRefGoogle Scholar
  13. 13.
    H. Kano, M. Kohno, K. Yasunari, K. Yokokawa, T. Horio, M. Ikeda, M. Minami, T. Hanehira, T. Takeda, J. Yoshikawa, Adrenomedullin as a novel antiproliferative factor of vascular smooth muscle cells. J. Hypertens. 14(2), 209–213 (1996)PubMedCrossRefGoogle Scholar
  14. 14.
    Y. Isumi, N. Minamino, T. Katafuchi, M. Yoshioka, T. Tsuji, K. Kangawa, H. Matsuo, Adrenomedullin production in fibroblasts: its possible function as a growth regulator of Swiss 3T3 cells. Endocrinology 139(5), 2552–2563 (1998)PubMedCrossRefGoogle Scholar
  15. 15.
    T. Shindo, Y. Kurihara, H. Nishimatsu, N. Moriyama, M. Kakoki, Y. Wang, Y. Imai, A. Ebihara, T. Kuwaki, K.H. Ju, N. Minamino, K. Kangawa, T. Ishikawa, M. Fukuda, Y. Akimoto, I. Szokdi, P. Kinnumen, P. Tavi, M. Weckstrom, M. Toth, H. Ruskoaho, Evidence for cAMP-independent mechanisms mediating the effects of adrenomedullin, a new inotropic peptide. Circulation 97, 1070–1082 (1998)Google Scholar
  16. 16.
    H. Yin, L. Chao, J. Chao, Adrenomedullin protects against myocardial apoptosis after ischemia/reperfusion through activation of Akt-GSK signaling. Hypertension 43(1), 109–116 (2004)PubMedCrossRefGoogle Scholar
  17. 17.
    S.A. Hamid, G.F. Baxter, A critical cytoprotective role of endogenous adrenomedullin in acute myocardial infarction. J. Mol. Cell. Cardiol. 41(2), 360–363 (2006)PubMedCrossRefGoogle Scholar
  18. 18.
    K.M. Caron, O. Smithies, Extreme hydrops fetalis and cardiovascular abnormalities in mice lacking a functional adrenomedullin gene. Proc. Natl. Acad. Sci. USA 98(2), 615–619 (2001)PubMedCrossRefGoogle Scholar
  19. 19.
    A. Vadivel, S. Abozaid, T. van Haaften, M. Sawicka, F. Eaton, M. Chen, B. Thebaud, Adrenomedullin promotes lung angiogenesis, alveolar development and repair. Am. J. Respir. Cell Mol. Biol. 43, 152–160 (2010)PubMedCrossRefGoogle Scholar
  20. 20.
    A.M. Elhawary, J. Poon, C.C. Pang, Effects of calcitonin gene related peptide antagonists on renal actions of adrenomedullin. Br. J. Pharmacol. 115, 1133–1140 (1995)PubMedGoogle Scholar
  21. 21.
    R.C. Vari, S.D. Adkins, W.K. Samson, Renal effects of adrenomedullin in the rat. Proc. Soc. Exp. Biol. Med. 211, 178–183 (1995)Google Scholar
  22. 22.
    P.G. Andreis, G. Neri, T. Prayer-Galetti, G.P. Rossi, G. Gottardo, etc. Effects of adrenomedullin on the human adrenal glands: an in vitro study. J. Clin. Endocrinol. Metab. 82, 1167–1170 (1997)Google Scholar
  23. 23.
    T. Yamaguchi, K. Baba, Y. Doi, K. Yano, Effect of adrenomedullin on aldosterone secretion by dispersed rat adrenal zona glomerulosa cells. Life Sci. 56, 379–387 (1995)PubMedCrossRefGoogle Scholar
  24. 24.
    M. Garayoa, E. Bodegas, F. Cuttitta, L.M. Montuenga. Adrenomedullin in mammalian embryogenesis. Microsc. Res. Tech. 57(1), 40–54 Review (2002)Google Scholar
  25. 25.
    G. Carraro, G. Albertin, S. Bova, L.K. Malendowicz, A.S. Belloni, G.G. Nussdorfer, Differential expression of adrenomedullin and its receptors in newborn and adult rat thymus. Int. J. Mol. Med. 10, 767–771 (2002)PubMedGoogle Scholar
  26. 26.
    Y.Y. Li, L. Li, I.S.S. Hwang, F. Tang, O. WS, Co-expression of adrenomedullin and its receptors in the reproductive system of the rat: effects on steroid secretion in the ovary. Biol. Reprod. 7, 200–208 (2008)CrossRefGoogle Scholar
  27. 27.
    H.W. Li, S.B. Liao, P.C. Chiu, W.W. Tam, J.C. Ho, E.H. Ng, P.C. Ho, W.S. Yeung, F. Tang, O. WS, Expression of adrenomedullin in human oviduct, its regulation by the hormonal cycle and contact with spermatozoa, and its effect on ciliary beat frequency of the oviductal epithelium. J. Clin. Endocrinol. Metab. 85, E18–E25 (2010)CrossRefGoogle Scholar
  28. 28.
    K.J. Livak, T.D. Schmittgen, Analysis of relative gene expression data using real-time quantitative PCR and the 2[-Delta Delta C(T)] method. Methods 25(4), 402–408 (2001)PubMedCrossRefGoogle Scholar
  29. 29.
    I.S. Hwang, D.J. Autelitano, P.Y. Wong, G.P. Leung, F. Tang, Co-expression of adrenomedullin and adrenomedullin receptors in rat epididymis: distinct physiological actions on anion transport. Biol. Reprod. 68(6), 2005–2012 (2003)PubMedCrossRefGoogle Scholar
  30. 30.
    Y.Y. Li, I.S.S. Hwang, O. WS, F. Tang, Adrenomedullin peptide, gene expression of adrenomedullin and its receptors and receptor activity modifying proteins and receptor binding in rat testis: actions on testosterone secretion. Biol. Reprod. 75, 183–188 (2006)PubMedCrossRefGoogle Scholar
  31. 31.
    S.Y. Man, I.S.S. Hwang, Y.Y. Li, O. WS, F. Tang, Differential regulation of adrenomedullin gene expression in the fundic and pyloric regions of the rat stomach during acute and chronic starvation. Neuropeptides 41, 177–187 (2007)PubMedCrossRefGoogle Scholar
  32. 32.
    L.M. Montuenga, A. Martinez, M.J. Miller, E.J. Unsworth, F. Cuttitta, Expression of adrenomedullin and its receptor during embryogenesis suggests autocrine or paracrine modes of action. Endocrinology 138, 440–451 (1997)PubMedCrossRefGoogle Scholar
  33. 33.
    F. Tang, M.P.F. Wong, I.S.S. Hwang, Y.Y. Li, Ether stress increases adrenomedullin gene expression and levels in the rat adrenal. Horm. Metabol. Res. 37, 585–588 (2005)CrossRefGoogle Scholar
  34. 34.
    F. Tang, J.G. Phillips, Pituitary-adrenal response to ether stress in the neonatal rat. J. Endocrinol. 75, 183–184 (1977)PubMedCrossRefGoogle Scholar
  35. 35.
    C.D. Walker, M. Perrin, W. Vale, C. Rivier, Ontogeny of the stress response in the rat: role of the pituitary and the hypothalamus. Endocrinology 118, 1445–1451 (1986)PubMedCrossRefGoogle Scholar
  36. 36.
    M.L Franco-Montoya, O. Boucherat, C. Thibault, B. Chailley-Heu, R. Incitti, C. Delacourt, J.R Bourbon. Profiling target genes of FGF18 in the postnatal mouse lung: possible relevance for alveolar development. Physiol Genomics (2011) [Epub ahead of print]Google Scholar
  37. 37.
    E. Marinoni, R. Di Iorio, P. Alo, B. Villaccio, A. Alberini, E.V. Cosmi, Immunohistochemical localization of adrenomedullin in fetal and neonatal lung. Pedeiatr Res 45, 282–285 (1999)CrossRefGoogle Scholar
  38. 38.
    M. Dvorakova, R.V. Haberberger, S. Hagner, G.P. McGregor, J. Slavikova, W. Kummer, Expression and distribution of the calcitonin receptor-like receptor in the developing rat heart. Anat Embryol (Berl) 207, 307–315 (2003)CrossRefGoogle Scholar
  39. 39.
    H. He, H. Besso, Y. Fujisawa, K. Horiuchi, A. Tomohireo, T. Kita, Y. Aki, S. Kimura, T. Tamaki, Y. Abe, Effects of a synthetic rat adrenomedullin on regional hemodynamics in rats. Eur. J. Pharmacol. 27, 209–214 (1995)CrossRefGoogle Scholar
  40. 40.
    T. Yoshimoto, N. Fukai, R. Sato, T. Sugiyama, N. Ozawa, M. Shichiri, Y. Hirata, Antioxidant effect of adrenomedullin on angiotensin II-induced reactive oxygen species generation in vascular smooth muscle. Endocrinology 145, 3331–3337 (2004)PubMedCrossRefGoogle Scholar
  41. 41.
    G. Clementi, A. Caruso, V.M. Cuuli, A. Prato, N.G. Mangano, M. Amico-roxas, Anti-inflammatory activity of adrenomedullin in the acetic acid peritonitis in rats. Life Sci. 65, PL203–PL208 (1999)PubMedCrossRefGoogle Scholar
  42. 42.
    L.Y. Wong, B.M. Cheung, Y.Y. Li, F. Tang, Adrenomedullin is both proinflammatory and anti-inflammatory: its effects on gene expression and secretion of cytokines and macrophage migration inhibitory factor in NR8383 macrophage cell line. Endocrinology 146, 1321–1327 (2005)PubMedCrossRefGoogle Scholar
  43. 43.
    G. Mazzocchi, F. Musajo, G. Neri, G. Gottardo, G.G. Nussdorfer, Adrenomedullin stimulates steroid secretion by the isolated perfused rat adrenal gland in situ: comparison with calcitonin gene-related peptide effects. Peptides 17, 853–857 (1996)PubMedCrossRefGoogle Scholar
  44. 44.
    T. Yamaguchi, K. Baba, Y. Doi, K. Yano, K. Kitamura, T. Eto, Inhibition of aldosterone production by adrenomedullin, a hypotensive peptide, in the rat. Hypertension 28, 308–314 (1996)PubMedGoogle Scholar
  45. 45.
    W.K. Samson, Adrenomedullin and the control of fluid and electrolyte homeostasis. Annu. Rev. Physiol. 61, 363–389 (1999)PubMedCrossRefGoogle Scholar
  46. 46.
    S. Kaufman, Y. Deng, Adrenomedullin suppresses atrial natriuretic factor (ANF) secretion from isolated atrium. Life Sci. 63, 1017–1022 (1998)PubMedCrossRefGoogle Scholar
  47. 47.
    I. Szokodi, P. Kinnunen, P. Tavi, M. Weckström, M. Tóth, H. Ruskoaho, Evidence for cAMP-independent mechanisms mediating the effects of adrenomedullin, a new inotropic peptide. Circulation 97(11), 1062–1070 (1998)PubMedGoogle Scholar
  48. 48.
    B. Semmekrot, J.P. Guignard, Atrial natriuretic peptide during early human development. Biol. Neonate 60, 341–349 (1991)PubMedCrossRefGoogle Scholar
  49. 49.
    H. Zink, M. Horster, Maturation of diluting capacity in loop of Henle of rat superficial nephrons. Am. J. Physiol. 233, F519–F524 (1977)PubMedGoogle Scholar
  50. 50.
    G. Falk, Maturation of renal function in infant rats. Am. J. Physiol. 181, 157–170 (1955)PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of PhysiologyLKS Faculty of Medicine, The University of Hong KongHong Kong SARChina
  2. 2.Department of AnatomyLKS Faculty of Medicine, The University of Hong KongHong Kong SARChina
  3. 3.Centre of Growth, Reproduction and DevelopmentLKS Faculty of Medicine, The University of Hong KongHong Kong SARChina
  4. 4.Centre of Heart, Brain, Hormone and Healthy AgingLKS Faculty of Medicine, The University of Hong KongHong Kong SARChina

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