Download PDF
Horm Metab Res 2012; 44(03): 228-233
DOI: 10.1055/s-0031-1301300
Humans, Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Association of IGF-I and the IGF-I/IGFBP-3 Ratio with Plasma Aldosterone Levels in the General Population

A. Hannemann   *
1   Institute of Clinical Chemistry and Laboratory Medicine, Ernst-Moritz-Arndt-University, Greifswald, Germany
,
H. Wallaschofski   *
1   Institute of Clinical Chemistry and Laboratory Medicine, Ernst-Moritz-Arndt-University, Greifswald, Germany
,
R. Rettig
2   Institute of Physiology, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany
,
H. Völzke
3   Institute for Community Medicine, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany
,
S. Samietz
4   Center of Oral Health, Policlinic of Prosthetic Dentistry, Gerodontology and Biomaterials, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany
,
M. Nauck
1   Institute of Clinical Chemistry and Laboratory Medicine, Ernst-Moritz-Arndt-University, Greifswald, Germany
,
M. Bidlingmaier
5   Medical Clinic Innenstadt, Ludwig-Maximilians-University Munich, Munich, Germany
,
N. Friedrich
1   Institute of Clinical Chemistry and Laboratory Medicine, Ernst-Moritz-Arndt-University, Greifswald, Germany
› Author Affiliations
Further Information

Publication History

received 16 June 2011

accepted 28 December 2011

Publication Date:
10 February 2012 (online)

Also available at
    Permissions and Reprints

Abstract

Several studies in patients with acromegaly or growth hormone (GH) deficiency suggest a stimulatory effect of the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis on the renin-angiotensin-aldosterone system (RAAS). We analyzed the association of serum IGF-I with plasma aldosterone and the aldosterone-to-renin ratio in a large sample from the general population. In addition to serum IGF-I levels, we also considered the IGF-I-to-IGF binding protein (IGFBP)-3 ratio. A total of 1 504 men and 1 566 women aged 25–88 were selected from the first follow-up of the population-based Study of Health in Pomerania. Plasma aldosterone and renin concentrations, as well as serum IGF-I and IGFBP-3 levels were determined with immunoassays. Analyses of variance and linear regression analyses were performed. We found positive associations between serum IGF-I or the IGF-I/IGFBP-3 ratio with plasma aldosterone in women but not in men. Plasma aldosterone levels increased by 2.91 ng/l per IGF-I standard deviation (SD) and by 2.17 ng/l per IGF-I/IGFBP-3 SD. The associations remained significant after exclusion of subjects taking RAAS-altering medication and of subjects with serum IGF-I levels and aldosterone-to-renin ratios outside the reference range. We conclude that, serum IGF-I and the IGF-I/IGFBP-3 ratio are associated with plasma aldosterone levels in women but not in men from the general population.

Key words

growth hormone - insulin-like growth factor I - renin-angiotensin-aldosterone system
*

*  These authors contributed equally to this work.


 

  • References

  • 1 Jogie-Brahim S, Feldman D, Oh Y. Unraveling insulin-like growth factor binding protein-3 actions in human disease. Endocr Rev 2009; 30: 417-437
    CrossrefPubMedSearch in Google Scholar
  • 2 Colao A. The GH-IGF-I axis and the cardiovascular system: clinical implications. Clin Endocrinol (Oxf) 2008; 69: 347-358
    CrossrefPubMedSearch in Google Scholar
  • 3 Melmed S. Acromegaly pathogenesis and treatment. J Clin Invest 2009; 119: 3189-3202
    CrossrefPubMedSearch in Google Scholar
  • 4 Brown NJ. Aldosterone and end-organ damage. Curr Opin Nephrol Hypertens 2005; 14: 235-241
    CrossrefPubMedSearch in Google Scholar
  • 5 Cachofeiro V, Miana M, de Las Heras N, Martin-Fernandez B, Ballesteros S, Fernandez-Tresguerres J, Lahera V. Aldosterone and the vascular system. J Steroid Biochem Mol Biol 2008; 109: 331-335
    CrossrefPubMedSearch in Google Scholar
  • 6 Mulatero P, Veglio F, Maffei P, Bondanelli M, Bovio S, Daffara F, Leotta G, Angeli A, Calvo C, Martini C, degli Uberti EC, Terzolo M. CYP11B2-344T/C gene polymorphism and blood pressure in patients with acromegaly. J Clin Endocrinol Metab 2006; 91: 5008-5012
    CrossrefPubMedSearch in Google Scholar
  • 7 Cuneo RC, Salomon F, Wilmshurst P, Byrne C, Wiles CM, Hesp R, Sonksen PH. Cardiovascular effects of growth hormone treatment in growth-hormone-deficient adults: stimulation of the renin-aldosterone system. Clin Sci (Lond) 1991; 81: 587-592
    PubMedSearch in Google Scholar
  • 8 Hoffman DM, Crampton L, Sernia C, Nguyen TV, Ho KK. Short-term growth hormone (GH) treatment of GH-deficient adults increases body sodium and extracellular water, but not blood pressure. J Clin Endocrinol Metab 1996; 81: 1123-1128
    CrossrefPubMedSearch in Google Scholar
  • 9 Moller J, Frandsen E, Fisker S, Jorgensen JO, Christiansen JS. Decreased plasma and extracellular volume in growth hormone deficient adults and the acute and prolonged effects of GH administration: a controlled experimental study. Clin Endocrinol (Oxf) 1996; 44: 533-539
    CrossrefPubMedSearch in Google Scholar
  • 10 Moller J, Fisker S, Rosenfalck AM, Frandsen E, Jorgensen JO, Hilsted J, Christiansen JS. Long-term effects of growth hormone (GH) on body fluid distribution in GH deficient adults: a four months double blind placebo controlled trial. Eur J Endocrinol 1999; 140: 11-16
    CrossrefPubMedSearch in Google Scholar
  • 11 Hanukoglu A, Belutserkovsky O, Phillip M. Growth hormone activates renin-aldosterone system in children with idiopathic short stature and in a pseudohypoaldosteronism patient with a mutation in epithelial sodium channel alpha subunit. J Steroid Biochem Mol Biol 2001; 77: 49-57
    CrossrefPubMedSearch in Google Scholar
  • 12 Ho KY, Weissberger AJ. The antinatriuretic action of biosynthetic human growth hormone in man involves activation of the renin-angiotensin system. Metabolism 1990; 39: 133-137
    CrossrefPubMedSearch in Google Scholar
  • 13 Lin C, Mendonca B, Lucon A, Guazzelli I, Noicolau W, Villares S. Growth hormone receptor messenger ribonucleic acid in normal and pathologic human adrenocortical tissues – an analysis by quantitative polymerase chain reaction technique. J Clin Endocrinol Metab 1997; 82: 2671-2676
    CrossrefPubMedSearch in Google Scholar
  • 14 Weber MM, Auernhammer CJ, Kiess W, Engelhardt D. Insulin-like growth factor receptors in normal and tumorous adult human adrenocortical glands. Eur J Endocrinol 1997; 136: 296-303
    CrossrefPubMedSearch in Google Scholar
  • 15 Fottner C, Engelhardt D, Elmlinger MW, Weber MM. Identification and characterization of insulin-like growth factor (IGF)-binding protein expression and secretion by adult human adrenocortical cells: differential regulation by IGFs and adrenocorticotropin. J Endocrinol 2001; 168: 465-474
    CrossrefPubMedSearch in Google Scholar
  • 16 Kamide K, Hori MT, Zhu JH, Takagawa Y, Barrett JD, Eggena P, Tuck ML. Insulin and insulin-like growth factor-I promotes angiotensinogen production and growth in vascular smooth muscle cells. J Hypertens 2000; 18: 1051-1056
    CrossrefPubMedSearch in Google Scholar
  • 17 Wyse B, Waters M, Sernia C. Stimulation of the renin-angiotensin system by growth hormone in Lewis dwarf rats. Am J Physiol 1993; 265: E332-E339
    PubMedSearch in Google Scholar
  • 18 Ekman B, Ohman PK, Arnqvist HJ, Lindstrom T, Nystrom FH. Individualized growth hormone substitution with normalized IGF-I levels does not stimulate the renin-angiotensin-aldosterone system. Clin Endocrinol (Oxf) 2002; 57: 473-479
    CrossrefPubMedSearch in Google Scholar
  • 19 Bielohuby M, Roemmler J, Manolopoulou J, Johnsen I, Sawitzky M, Schopohl J, Reincke M, Wolf E, Hoeflich A, Bidlingmaier M. Chronic growth hormone excess is associated with increased aldosterone: a study in patients with acromegaly and in growth hormone transgenic mice. Exp Biol Med (Maywood) 2009; 234: 1002-1009
    CrossrefPubMedSearch in Google Scholar
  • 20 Volzke H, Alte D, Schmidt CO, Radke D, Lorbeer R, Friedrich N, Aumann N, Lau K, Piontek M, Born G, Havemann C, Ittermann T, Schipf S, Haring R, Baumeister SE, Wallaschofski H, Nauck M, Frick S, Arnold A, Junger M, Mayerle J, Kraft M, Lerch MM, Dorr M, Reffelmann T, Empen K, Felix SB, Obst A, Koch B, Glaser S, Ewert R, Fietze I, Penzel T, Doren M, Rathmann W, Haerting J, Hannemann M, Ropcke J, Schminke U, Jurgens C, Tost F, Rettig R, Kors JA, Ungerer S, Hegenscheid K, Kuhn JP, Kuhn J, Hosten N, Puls R, Henke J, Gloger O, Teumer A, Homuth G, Volker U, Schwahn C, Holtfreter B, Polzer I, Kohlmann T, Grabe HJ, Rosskopf D, Kroemer HK, Kocher T, Biffar R, John U, Hoffmann W. Cohort Profile: The Study of Health in Pomerania. Int J Epidemiol 2011; 40: 294-307
    CrossrefPubMedSearch in Google Scholar
  • 21 Juul A. Serum levels of insulin-like growth factor I and its binding proteins in health and disease. Growth Horm IGF Res 2003; 13: 113-170
    CrossrefPubMedSearch in Google Scholar
  • 22 Brugts MP, Ranke MB, Hofland LJ, van der Wansem K, Weber K, Frystyk J, Lamberts SW, Janssen JA. Normal values of circulating insulin-like growth factor-I bioactivity in the healthy population: comparison with five widely used IGF-I immunoassays. J Clin Endocrinol Metab 2008; 93: 2539-2545
    CrossrefPubMedSearch in Google Scholar
  • 23 Gatford KL, Egan AR, Clarke IJ, Owens PC. Sexual dimorphism of the somatotrophic axis. J Endocrinol 1998; 157: 373-389
    CrossrefPubMedSearch in Google Scholar
  • 24 Friedrich N, Krebs A, Nauck M, Wallaschofski H. Age- and gender-specific reference ranges for serum insulin-like growth factor I (IGF-I) and IGF-binding protein-3 concentrations on the Immulite 2500: results of the Study of Health in Pomerania (SHIP). Clin Chem Lab Med 2010; 48: 115-120
    CrossrefPubMedSearch in Google Scholar
  • 25 Hannemann A, Friedrich N, Ludemann J, Volzke H, Rettig R, Peters J, Reincke M, Doring A, Nauck M, Wallaschofski H. Reference intervals for aldosterone, renin, and the aldosterone-to-renin ratio in the population-based Study of Health in Pomerania (SHIP-1). Horm Metab Res 2010; 42: 392-399
    Thieme ConnectPubMedSearch in Google Scholar
  • 26 Moller J, Moller N, Frandsen E, Wolthers T, Jorgensen JO, Christiansen JS. Blockade of the renin-angiotensin-aldosterone system prevents growth hormone-induced fluid retention in humans. Am J Physiol 1997; 272: E803-E808
    PubMedSearch in Google Scholar
  • 27 Vasan RS, Evans JC, Larson MG, Wilson PW, Meigs JB, Rifai N, Benjamin EJ, Levy D. Serum aldosterone and the incidence of hypertension in nonhypertensive persons. N Engl J Med 2004; 351: 33-41
    Search in Google Scholar
  • 28 Bondanelli M, Ambrosio MR, degli Uberti EC. Pathogenesis and prevalence of hypertension in acromegaly. Pituitary 2001; 4: 239-249
    CrossrefPubMedSearch in Google Scholar
  • 29 Johannsson G, Sverrisdottir YB, Ellegard L, Lundberg PA, Herlitz H. GH increases extracellular volume by stimulating sodium reabsorption in the distal nephron and preventing pressure natriuresis. J Clin Endocrinol Metab 2002; 87: 1743-1749
    CrossrefPubMedSearch in Google Scholar
  • 30 Moller J, Jorgensen JO, Marqversen J, Frandsen E, Christiansen JS. Insulin-like growth factor I administration induces fluid and sodium retention in healthy adults: possible involvement of renin and atrial natriuretic factor. Clin Endocrinol (Oxf) 2000; 52: 181-186
    CrossrefPubMedSearch in Google Scholar
  • 31 Geary MP, Pringle PJ, Rodeck CH, Kingdom JC, Hindmarsh PC. Sexual dimorphism in the growth hormone and insulin-like growth factor axis at birth. J Clin Endocrinol Metab 2003; 88: 3708-3714
    CrossrefPubMedSearch in Google Scholar
  • 32 Meinhardt UJ, Ho KK. Modulation of growth hormone action by sex steroids. Clin Endocrinol (Oxf) 2006; 65: 413-422
    CrossrefPubMedSearch in Google Scholar
  • 33 Span JP, Pieters GF, Sweep FG, Hermus AR, Smals AG. Gender differences in rhGH-induced changes in body composition in GH-deficient adults. J Clin Endocrinol Metab 2001; 86: 4161-4165
    CrossrefPubMedSearch in Google Scholar
  • 34 Burman P, Johansson AG, Siegbahn A, Vessby B, Karlsson FA. Growth hormone (GH)-deficient men are more responsive to GH replacement therapy than women. J Clin Endocrinol Metab 1997; 82: 550-555
    CrossrefPubMedSearch in Google Scholar