Int J Sports Med 2004; 25(3): 205-208
DOI: 10.1055/s-2003-45261
Physiology & Biochemistry

© Georg Thieme Verlag Stuttgart · New York

Growth Hormone (GH) Isoforms Following Acute 22-kDa GH Injection: Is it Useful to Detect GH Abuse?

G. Radetti1 , F. Buzi2 , G. Tonini3 , J. Bellone4 , S. Pagani5 , M. Bozzola5
  • 1Department of Paediatrics, Regional Hospital of Bolzano, Italy
  • 2Department of Paediatrics, University of Brescia, Italy
  • 3Department of Paediatrics, University of Trieste, IRCCS Burlo Garofolo, Italy
  • 4Division of Paediatric Endocrinology, Regina Margherita Children’s Hospital, Turin, Italy
  • 5Department of Paediatrics, University of Pavia, Italy
Further Information

Publication History

Accepted after revision: July 20, 2003

Publication Date:
15 April 2004 (online)

Abstract

The aim of the study was to investigate the influence of an acute administration of 22-kDa hGH (22-kDa GH) on 22-kDa GH and 20-kDa GH serum levels, biological activity of GH (Nb2-GH) and on 22-kDa/20-kDa GH ratio, in order to verify whether the assessment of the GH isoforms could be a potential tool for diagnosing GH abuse. Twenty-eight children (21 M, 7 F), age 10.4 ± 0.8 y, affected by idiopathic isolated GH deficiency and 10 children (8 M, 2 F), age 9.2 ± 2.3 y affected by constitutional growth delay, were evaluated. After an overnight fast, a basal blood sample was obtained between 8 a.m. and 9 a.m. and a dose of 22-kDa GH was then administered subcutaneously (0.1U/Kg). Blood was drawn after 2, 4 and 6 h, for the evaluation of 22-kDa GH, Nb2-GH and 20-kDa GH serum levels. Similar results were obtained in patients and controls: a significant rise, although of variable amplitude, of 22-kDa GH and Nb2-GH was found (p < 0.001) and the maximum peak was detected after 4 h in the majority of subjects. No acute changes in 20-kDa GH serum levels were observed. The 22-kDa/20-kDa GH ratio increased progressively, due to the rising levels of 22-kDa GH. A positive correlation was seen between 22-kDa GH and Nb2-GH levels at baseline and at 2, 4 and 6 h (p < 0.014, r = 0.99). Since in normal subjects the ratio of endogenous 22-kDa GH and 20-kDa GH is constant, an altered ratio of 22-kDa/20-kDa GH is highly suggestive of GH abuse. The short period of time available for the evaluation however (within 3 h from GH injection), severely limits this investigational tool in athletes.

References

  • 1 Baumann G, Winter R J, Shaw M. Circulating molecular variants of growth hormone in childhood.  Pediatr Res. 1987;  22 21-22
  • 2 Baumann G. Growth hormone binding proteins and various forms of growth hormone: implication for measurements.  Acta Paediatr Scand (Suppl). 1990;  370 72-80
  • 3 Baumann G. Growth hormone heterogeneity: genes, isohormones, variants and binding proteins.  Endocr Rev. 1991;  12 424-449
  • 4 Berglund B, Wide L. Erythropoietin concentrations and isoforms in urine of anonymous Olympic athletes during the Nagano Olympic Games.  Scand J Med Sci Sports. 2002;  12 354-357
  • 5 Berglund B, Aulin K P, Wide L. Effect of short-term and intermittent normobaric hypoxia on endogenous erythropoietin isoforms.  Scand J Med Sci Sports. 2003;  13 124-127
  • 6 Bozzola M, Zecca M, Locatelli F, Radetti G, Pagani S, Autelli M, Tatò L, Chatelain P. Evaluation of growth hormone bioactivity using the Nb2 cell bioassay in children with growth disorders.  J Endocrinol Invest. 1998;  21 765-770
  • 7 Cooke N E, Ray J, Watson M A, Estes P A, Kuo B A, Liebhaber S A. Human growth hormone gene and the highly homologous growth hormone variant gene display different splicing patterns.  J Clin Invest. 1988;  82 270-275
  • 8 Cowell C T. Short stature. In: Brook CGD (ed) Clinical Paediatric Endocrinology. 3rd edition. Oxford: Blackwell Science 1994: 136-172
  • 9 DeNoto F M, Moore D D, Goodman H M. Human growth hormone DNA sequence and mRNA structure: possible alternative splicing.  Nucleic Acids Res. 1981;  9 3719-3730
  • 10 Greulich W W, Pyle S L. Radiographic Atlas of Skeletal Development of the Hand and Wrist. 2nd ed. Stanford, CA: Stanford University Press 1969
  • 11 Ishikawa M, Yokoya S, Tachibana K, Hasegawa Y, Yasuda T, Tokuhiro E, Hashimoto Y, Tanaka T. Serum levels of 20-kilodalton human growth hormone (GH) are parallel to those of 22-kilodalton human GH in normal and short children.  J Clin Endocrinol Metab. 1999;  84 98-104
  • 12 Lewis U J, Dunn J T, Bonewald L F, Seavey B K, Vanderlaan W P. A naturally occurring structural variant of human growth hormone.  J Biol Chem. 1978;  253 2679-2687
  • 13 Lewis U J, Bonewald L F, Lewis L J. The 20,000-dalton variant of human growth hormone: location of the amino acid deletions.  Biochem Biophys Res Commun. 1980;  92 512-516
  • 14 Momomura S, Hashimoto Y, Shimazaki Y, Irie M. Detection of exogenous growth hormone (GH) administration by monitoring ratio of 20-kDaDa- and 22-kDaDa-GH in serum and urine.  Endocr J. 2000;  47 97-101
  • 15 Radetti G, Bozzola M, Pagani S, Avanzini M A, Messner H, Belloni C, Hayakawa M. Circulating growth hormone (GH) isoforms and GH bioactivity in preterm neonates.  Pediatr Res. 2000;  48 244-247
  • 16 Rolland-Cachera M F, Cole T J, Sempé M, Tichet J, Rossignol C, Charraud A. Body mass index variations: centile from birth to 87 years.  Eur J Clin Nutr. 1991;  45 13-21
  • 17 Tanaka T, Shiu R PC, Gout P J, Beer C T, Noble R L, Friesen H G. A new sensitive and specific bioassay for lactogenic hormones: measurements of prolactin and growth hormone in human serum.  J Clin Endocrinol Metab. 1980;  51 1058-1063
  • 18 Tanner J M, Whitehouse R H, Takaishi M. Standards from birth to maturity for height, weight, height velocity and weight velocity: British children.  Arch Dis Child. 1966;  41 613-635
  • 19 Tanner J M. Foetus into man: physical growth from conception to maturity. Second Edition, Castelmead Publications, Ware 1989
  • 20 Walker A, Croze F, Friesen H G. A serum-free medium for culturing lactogen dependent and autonomous Nb2 node lymphoma cells.  Endocrinology. 1987;  120 2389-2397
  • 21 Wallace J D, Cuneo R C. Growth hormone abuse in Athletes. A review.  The Endocrinologist. 2000;  10 175-184
  • 22 Wallace J D, Cuneo R C, Bidlingmaier M, Lundberg P A, Carlsson L, Boguszewski C L, Hay J, Boroujerdi M, Cittadini A, Dall R, Rosén T, Strasburger C J. Changes in non-22-Kilodalton (kDa) isoforms of growth hormone (GH) after administration of 22-kDa recombinant human GH in trained adult males.  J Clin Endocrinol Metab. 2001;  86 1731-1737

G. Radetti

Department of Paediatrics, Regional Hospital of Bolzano

via L. Boehler 5 · 39100 Bolzano· Italy

Phone: +39-0471/908651

Fax: 39-0471/909730

Email: giorgio.radetti@asbz.it

    >