Endocrine Control and Regulation of Growth Hormone: An Overview

Chapter

Abstract

The control of growth hormone (GH) production is complex, partly because GH serves both metabolic and anabolic roles. GH exerts potent anti-insulin effects at hepatic and peripheral sites and increases fat mobilization and lipolysis. IGF-I, a critical growth factor induced by GH, is likely responsible for most anabolic (on lean mass and bone mineralization) and growth-promoting (on growth plate) activities of GH, which also requires sufficient energy stores. GH secretion is regulated by hypothalamic growth hormone-releasing hormone (GHRH) and somatostatin interacting with circulating hormones, metabolic regulators, neurotransmitters, and additional modulatory peptides at the level of both the pituitary and the hypothalamus. Age, puberty, gender, sleep, exercise, food intake, and body composition are physiological determinants of GH secretion. Numerous hormones (ghrelin, sex steroids, glucocorticoids, thyroid hormones, insulin, glucagon, leptin, GH itself, and IGF-1) and metabolic regulators (glucose, amino acids, free fatty acids) control GH. “Normal” GH secretion covers a broad range of GH concentrations, and the definition of thresholds for GH deficiency following stimulation tests or integrated GH concentration measurement over 24 h proves to be difficult. There is no gold standard for GHD diagnosis, which relies on medical history, auxology, IGF-1/IGFBP3 measurements, GH provocative tests, and magnetic resonance imaging findings.

Keywords

Cholesterol Dopamine Testosterone Histamine NMDA 

Abbreviations

ALS

Acid-labile subunit

BMI

Body mass index

GH

Growth hormone

GHBP

Growth hormone-binding protein

GHD

Growth hormone deficiency

GHR

GH receptor

GHRH

Growth hormone-releasing hormone

GHRP

GH-releasing peptides

GHS-R

Growth hormone secretagogue receptor

GPCR

G protein-coupled receptor

IGF-I

Insulin-like growth factor I

IGFBP

IGF-binding protein

JAK

Janus kinase

rhGH

Recombinant human growth hormone

SGA

Small for gestational age

SOCS

Suppressors of cytokine signaling

SSTR

Somatostatin receptor

STAT

Signal transducers and activators of transcription

References

  1. Besson A, Salemi S, Deladoey J, Vuissoz JM, Eble A, Fluck C, Mullis PE. Short stature caused by a biologically inactive mutant growth hormone (GH-C53S). J Clin Endocrinol Metab. 2005;90:2493–9.PubMedCrossRefGoogle Scholar
  2. Bougneres P. The exon-3 deletion of the growth hormone receptor (GHR) gene still has a limited impact in clinical endocrinology. J Clin Endocrinol Metab. 2010;95:56–9.PubMedCrossRefGoogle Scholar
  3. Bowers CY. Unnatural growth hormone-releasing peptide begets natural ghrelin. J Clin Endocrinol Metab. 2001;86:1464–9.PubMedCrossRefGoogle Scholar
  4. Carel JC, Tresca JP, Letrait M, Chaussain JL, Lebouc Y, Job JC, Coste J. Growth hormone testing for the diagnosis of growth hormone deficiency in childhood: a population register-based study. J Clin Endocrinol Metab. 1997;82:2117–21.PubMedCrossRefGoogle Scholar
  5. Clement K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, Gourmelen M, Dina C, Chambaz J, Lacorte JM, Basdevant A, Bougneres P, Lebouc Y, Froguel P, Guy-Grand B. A mutation in the leptin receptor gene causes obesity and pituitary dysfunction. Nature 1998;392:398–401.PubMedCrossRefGoogle Scholar
  6. Coutant R, Boux de Casson F, Douay O, Mathieu E, Rouleau S, Beringue F, Gillard P, Limal JM, Descamps P. Relationships between placental GH concentration and maternal smoking, newborn gender, and maternal leptin: possible implications for birth weight. J Clin Endocrinol Metab 2001;86:4854–9.PubMedCrossRefGoogle Scholar
  7. Coutant R, Lahlou N, Bouvattier C, Bougneres P. Circulating leptin level and growth hormone response to stimulation tests in obese and normal children. Eur J Endocrinol. 1998;139:591–7.PubMedCrossRefGoogle Scholar
  8. GH Research Society. Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. J Clin Endocrinol Metab. 2000;85:3990–93.CrossRefGoogle Scholar
  9. Giustina A, Veldhuis JD. Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev. 1998;19:717–97.PubMedCrossRefGoogle Scholar
  10. Goddard AD, Covello R, Luoh SM, Clackson T, Attie KM, Gesundheit N, Rundle AC, Wells JA, Carlsson LM. Mutations of the growth hormone receptor in children with idiopathic short stature. The Growth Hormone Insensitivity Study Group. N Engl J Med. 1995;333:1093–8.PubMedCrossRefGoogle Scholar
  11. Hill DJ, Riley SC, Bassett NS, Waters MJ. Localization of the growth hormone receptor, identified by immunocytochemistry, in second trimester human fetal tissues and in placenta throughout gestation. J Clin Endocrinol Metab. 1992;75:646–50.PubMedCrossRefGoogle Scholar
  12. Iranmanesh A, Lizarralde G, Veldhuis J. Age and relative adiposity are specific negative determinants of the frequency and amplitude of growth hormone (GH) secretory bursts and the half-life of endogenous GH in healthy men. J Clin Endocrinol Metab. 1991;73:1081–8.PubMedCrossRefGoogle Scholar
  13. Kofoed EM, Hwa V, Little B, Woods KA, Buckway CK, Tsubaki J, Pratt KL, Bezrodnik L, Jasper H, Tepper A, Heinrich J, Rosenfeld RG. Growth-hormone insensitivity (GHI) associated with a STAT-5b mutation. N Engl J Med. 2003;349:1139–47.PubMedCrossRefGoogle Scholar
  14. Kojima M, Hosada H, Data Y, Nakazato M, Matsuo H, Kankawa K. Ghrelin is a growth-hormone releasing acylated peptide from stomach. Nature 1999;402:656–60.PubMedCrossRefGoogle Scholar
  15. Kopchick JJ, Parkinson C, Stevens EC, Trainer PJ. Growth hormone receptor antagonists: discovery, development, and use in patients with acromegaly. Endocr Rev. 2002;23:623–46.PubMedCrossRefGoogle Scholar
  16. Kowarski AA, Schneider J, Ben-Galim E, Weldon VV, Daughaday WH. Growth failure with normal serum RIA-GH and low somatomedin activity: somatomedin restoration and growth acceleration after exogenous GH. J Clin Endocrinol Metab. 1978;72:461–4.CrossRefGoogle Scholar
  17. Leger J, Oury JF, Noel M, Baron S, Benali K, Blot P, Czernichow P. Growth factors and intrauterine growth retardation. I. Serum growth hormone, insulin-like growth factor (IGF)-I, IGF-II, and IGF binding protein 3 levels in normally grown and growth-retarded human fetuses during the second half of gestation. Pediatr Res. 1996;40:94–100.PubMedCrossRefGoogle Scholar
  18. Marin G, Domene H, Barnes K, Blackwell B, Cassorla F, Cutler G, Jr. The effects of estrogen priming and puberty on the growth hormone response to standardized treadmill exercise and arginine-insulin in normal girls and boys. J Clin Endocrinol Metab. 1994;79:537–41.PubMedCrossRefGoogle Scholar
  19. Martinez AS, Domene HM, Ropelato MG, Jasper HG, Pennisi PA, Escobar ME, Heinrich JJ. Estrogen priming effect on growth hormone (GH) provocative test: a useful tool for the diagnosis of GH deficiency. J Clin Endocrinol Metab. 2000;85:4168–72.PubMedCrossRefGoogle Scholar
  20. Mulchahey JJ, DiBlasio AM, Martin MC, Blumenfeld Z, Jaffe RB. Hormone production and peptide regulation of the human fetal pituitary gland. Endocr Rev. 1987;8:406–25.PubMedCrossRefGoogle Scholar
  21. Pantel J, Legendre M, Cabrol S, Hilal L, Hajaji Y, Morisset S, Nivot S, Vie-Luton M-P, Grouselle D, de Kerdanet M, Kadiri A, Epelbaum J, Le Bouc Y, Amselem S. Loss of constitutive activity of the growth hormone secretagogue receptor in familial short stature. J Clin Invest. 2006;116:760–8.PubMedCrossRefGoogle Scholar
  22. Pinto G, Netchine I, Sobrier ML, Brunelle F, Souberbielle JC, Brauner R. Pituitary stalk interruption syndrome: a clinical-biological-genetic assessment of its pathogenesis. J Clin Endocrinol Metab. 1997;82:3450–4.PubMedCrossRefGoogle Scholar
  23. Reiter EW, Rosenfeld RG. Normal and aberrant growth. In: Larsen PR, Kronenberg HM, Melmed S, Polonski KS, editors. Williams textbook of endocrinology. 10th ed. Philadelphia, PA: Saunders; 2003. pp. 1003–14.Google Scholar
  24. Rochiccioli P, Enjaume C, Tauber MT, Pienkowski C. Statistical study of 5473 results of nine pharmacological stimulation tests: a proposed weighting index. Acta Paediatr. 1993;82:245–8.PubMedCrossRefGoogle Scholar
  25. Rosenfeld RG, Rosenbloom AL, Guevara-Aguirre J. Growth hormone (GH) insensitivity due to primary GH receptor deficiency. Endocr Rev. 1994;15:369–90.PubMedGoogle Scholar
  26. Takahashi Y, Shirono H, Arisaka O, Takahashi K, Yagi T, Koga J, Kaji H, Okimura Y, Abe H, Tanaka T, Chihara K. Biologically inactive growth hormone caused by an amino acid substitution. J Clin Invest. 1997;100:1159–65.PubMedCrossRefGoogle Scholar
  27. Tartaglia M, Mehler EL, Goldberg R, Zampino G, Brunner HG, Kremer H, van der Burgt I, Crosby AH, Ion A, Jeffery S, Kalidas K, Patton MA, Kucherlapati RS, Gelb BD. Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat Genet. 2001;29:465–8.PubMedCrossRefGoogle Scholar
  28. Toogood AA, Nass RM, Pezzoli SS, O’Neill PA, Thorner MO, Shalet SM. Preservation of growth hormone pulsatility despite pituitary pathology, surgery, and irradiation. J Clin Endocrinol Metab. 1997;82:2215–21.PubMedCrossRefGoogle Scholar
  29. Waters MJ, Kaye PL. The role of growth hormone in fetal development. GH and IGF Res. 2002;12:137–46.Google Scholar
  30. Zadik Z, Chalew SA, McCarter RJ, Jr., Meistas M, Kowarski AA. Assessment of growth hormone secretion in normal stature children using 24-hour integrated concentration of GH and pharmacological stimulation. J Clin Endocrinol Metab. 1985;60:513–6.PubMedCrossRefGoogle Scholar
  31. Zadik Z, Chalew SA, Kowarski A. The influence of age of 24-hour integrated concentration of growth hormone in normal individuals. J Clin Endocrinol Metab. 1990;71:932–6.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Pediatric Endocrinology Unit, Department of PediatricsUniversity HospitalAngers Cedex 01France

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