Genetic Defects in Processing Growth Hormone

  • John A. PhillipsIII
Part of the Serono Symposia, USA book series (SERONOSYMP)


Progress in recombinant DNA technology has enabled characterization of the sequence and organization of the hGH gene and the hGH gene cluster. This chapter reviews these findings and their pertinence to hGH expression in normal tissues as well as their derangements in selected genetic types of hGH deficiency.


Growth Hormone Human Growth Hormone Isolate Growth Hormone Deficiency Autosomal Recessive Mode Growth Hormone Gene Expression 
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  1. 1.
    Phillips JA III, Parks JS, Hjelle BL, et al. Genetic basis of familial isolated growth hormone deficiency type I. J Clin Invest 1982; 70: 489.PubMedCrossRefGoogle Scholar
  2. 2.
    Barsh GS, Seeburg PH, Gelinas RE. The human growth hormone gene family: structure and evolution of the chromosomal locus. Nucleic Acids Res 1983; 11: 3939.PubMedCrossRefGoogle Scholar
  3. 3.
    Hirt H, Kimelman J, Birnbaum MJ, et al. The human growth hormone gene locus: structure, evolution, and allelic variations. DNA 1987; 6: 59.PubMedCrossRefGoogle Scholar
  4. 4.
    Seeburg PH. The human growth hormone gene family: nucleotide sequences show recent divergence and predict a new polypeptide hormone. DNA 1982; 1: 239.PubMedCrossRefGoogle Scholar
  5. 5.
    Pavlakis GN, Hizuka N, Gorden P, Seeburg P, Hamer DH. Expression of two human growth hormone genes in monkey cells infected by simian virus 40 recombinants. Proc Natl Acad Sci USA 1981; 78: 7398.PubMedCrossRefGoogle Scholar
  6. 6.
    Miller WL, Eberhardt NL. Structure and evolution of the growth hormone gene family. Endocr Rev 1983; 4: 97.PubMedCrossRefGoogle Scholar
  7. 7.
    Wieringa B, Meyer F, Reiser J, Weissman C. Unusual splice sites revealed by mutagenic inactivation of an authentic splice site of the rabbit, 3-globin gene. Nature 1983; 301: 38.PubMedCrossRefGoogle Scholar
  8. 8.
    Lingappa VR, Blobel G. Early events in the biosynthesis of secretory and membrane proteins: the signal hypothesis. Recent Prog Horm Res 1980; 36: 451.PubMedGoogle Scholar
  9. 9.
    Lewis UJ, Singh RNP, Tutwiler GF, Sigel MB, Vanderlaan EF, Vanderlaan WP. Human growth hormone: a complex of proteins. Recent Prog Horm Res 1980; 36: 477.PubMedGoogle Scholar
  10. 10.
    Lewis UJ, Bonewald LF, Lewis LJ. The 20,000-dalton variant of human growth hormone: location of the amino acid deletions. Biochem Biophys Res Commun 1980; 92: 511.PubMedCrossRefGoogle Scholar
  11. 11.
    Denoto F, Moore DD, Goodman HM. Human growth hormone DNA sequence and mRNA structures: possible alternative splicing. Nucleic Acids Res 1981; 9: 3719.PubMedCrossRefGoogle Scholar
  12. 12.
    Moore DD, Walker MD, Diamond DJ, Conkling MA, Goodman HM. Structure, expression, and evolution of growth hormone genes. Recent Prog Horm Res 1982; 38: 197.PubMedGoogle Scholar
  13. 13.
    Seif I, Khoury G, Dhar R. BKV splice sequences based on analysis of preferred donor and acceptor sites. Nucleic Acids Res 1979; 6: 3387.PubMedCrossRefGoogle Scholar
  14. 14.
    Chawla RK, Parks JS, Rudman D. Structural variants of human growth hormone: biochemical, genetic, and clinical aspects. Annu Rev Med 1983; 34: 519.PubMedCrossRefGoogle Scholar
  15. 15.
    Evans RM, Birnberg NC, Rosenfeld MG. Glucocorticoid and thyroid hormones transcriptionally regulate growth hormone gene expression. Proc Natl Acad Sci USA 1982; 79: 7659.PubMedCrossRefGoogle Scholar
  16. 16.
    Barinaga M, Yamonoto G, Rivier C, Vale W, Evans E, Rosenfeld MG. Transcriptional regulation of growth hormone gene expression by growth hormone-releasing factor. Nature 1983; 306: 84.PubMedCrossRefGoogle Scholar
  17. 17.
    Martin JB. Neural regulation of growth hormone secretion. N Engl J Med 1973; 288: 1384.PubMedCrossRefGoogle Scholar
  18. 18.
    Wehrenberg WB, Ling N, Bohlen P, Esch F, Brazeau P, Guillemin R. Physiological roles of somatocrinin and somatostatin in the regulation of growth hormone secretion. Biochem Biophys Res Commun 1982; 109: 562.PubMedCrossRefGoogle Scholar
  19. 19.
    Grossman A, Savage MO, Besser GM. Growth hormone releasing hormone. Clin Endocrinol Metab 1986; 15: 607.PubMedCrossRefGoogle Scholar
  20. 20.
    Brazeau P, Epelbaum J, Tannenbaum GS, et al. Somatostatin: isolation, characterization, distribution, and blood determination. Metabolism 1978; 27: 1133.PubMedCrossRefGoogle Scholar
  21. 21.
    Kasting NW, Martin JB, Arnold MA. Pulsatile somatostatin release from the median eminence of the unanesthetized rat and its relationship to plasma growth hormone levels. Endocrinol 1981; 109: 1739.CrossRefGoogle Scholar
  22. 22.
    Vimpani GV, Vimpani AF, Lidgard GP, Cameron EHD, Farquhar JW. Prevalence of severe growth hormone deficiency. Br Med J 1977; 2: 427.PubMedCrossRefGoogle Scholar
  23. 23.
    Rona RJ, Tanner JM. Aetiology of idiopathic growth hormone deficiency in England and Wales. Arch Dis Child 1977; 52: 197.PubMedCrossRefGoogle Scholar
  24. 24.
    Lacey KA, Parkin JM. Causes of short stature—a community study of children in New Castle upon Tyne. Lancet 1974; i:42.Google Scholar
  25. 25.
    Tanner JM. Human growth hormone. Nature 1972; 237: 433.PubMedCrossRefGoogle Scholar
  26. 26.
    Seip M, Trygstad O, Aarskog D. Comment on pituitary dwarfism in Norway, 1961–1970. Birth Defects, Original Article Series 1971; 7: 33.Google Scholar
  27. 27.
    Gluckman PD, Grumbach MM, Kaplan SL. The neuroendocrine regulation and function of growth hormone and prolactin in the mammalian fetus. Endocr Rev 1981; 2: 363.PubMedCrossRefGoogle Scholar
  28. 28.
    Sara VR, Hall K, Rodeck CH, Wetterberg L. Human embryonic somatomedin. Proc Natl Acad Sci USA 1981; 78: 3175.PubMedCrossRefGoogle Scholar
  29. 29.
    Illig R, Prader A, Ferrandez A, Zachmann M. Hereditary prenatal growth hormone deficiency with increased tendency to growth hormone antibody formation (“A-type” isolated growth hormone deficiency). Acta Pediatr Scand [Suppl] 1971; 60: 607.Google Scholar
  30. 30.
    Phillips JA III, Hjelle BL, Seeburg PH, Zachmann M. Molecular basis for familial isolated growth hormone deficiency. Proc Natl Acad Sci 1981; 78: 6372.PubMedCrossRefGoogle Scholar
  31. 31.
    Phillips JA III, Ferrandez A, Frisch H, Illig R, Zuppinger K. Defects of GH genes. In: Raiti S, ed. Clinical syndromes in human growth hormone. New York: Plenum Publishing Corp., 1986: 211 - 26.CrossRefGoogle Scholar
  32. 32.
    Hauffa BP. Personal communication.Google Scholar
  33. 33.
    Laron Z, Kelijman M, Pertzelan A, Keret R, Shoffner JM, Parks JS. Human growth hormone gene deletion without antibody formation or growth arrest during treatment—a new disease entity? Isr J Med Sci 1985; 21: 999.PubMedGoogle Scholar
  34. 34.
    Goossens M, Brauner R, Czernichow P, Duquesnoy P, Rappaport R. Isolated growth hormone (GH) deficiency type 1A associated with a double deletion in the human GH gene cluster. J Clin Endocrinol Metab 1986; 62: 712.PubMedCrossRefGoogle Scholar
  35. 35.
    Wurzel JM, Parks JS, Herd JE, Nielsen PV. A gene deletion is responsible for absence of human chorionic somatomammotropin. DNA 1982; 1: 251.PubMedCrossRefGoogle Scholar
  36. 36.
    Parks JS, Nielsen PV, Sexton LA, Jorgensen EH. An effect of gene dosage on production of human chorionic sommatomammotropin. J Clin Endocrinol Metab 1985; 60: 994.PubMedCrossRefGoogle Scholar
  37. 37.
    Rogol AD, Blizzard RM, Foley TP Jr, et al. Growth hormone releasing hormone and growth hormone: genetic studies in familial growth hormone deficiency. Pediatr Res 1985; 19: 489.PubMedCrossRefGoogle Scholar
  38. 38.
    Rimoin DL. Genetic disorders of the pituitary gland. In: Emery AEH, Rimoin DL, eds. Principles and practice of medical genetics. Edinburgh: Churchill Livingstone, 1983: 1134.Google Scholar
  39. 39.
    Van Gelderen HH, Van Der Hoog CE. Familial isolated growth hormone deficiency. Clin Genet 1981; 20: 173.PubMedCrossRefGoogle Scholar
  40. 40.
    Fleisher TA, White RM, Broder S. X-linked hypogammaglobulinemia and isolated growth hormone deficiency. N Engl J Med 1980; 302: 1429.PubMedCrossRefGoogle Scholar
  41. 41.
    Rudman D, Kutner MH, Blackston RD, Cushman RA, Bain RP, Patterson JH. Children with normal-variant short stature: treatment with human growth hormone for six months. N Engl J Med 1981; 305: 123.PubMedCrossRefGoogle Scholar
  42. 42.
    Pertzelan A, Adam A, Laron Z. Genetic aspects of pituitary dwarfism due to absence or biological inactivity of growth hormone. Isr J Med Sci 1968; 4: 895.PubMedGoogle Scholar
  43. 43.
    Jacobs LS, Sneid SD, Garland JT, Laron Z, Daughaday WH. Receptor- active growth hormone in Laron dwarfism. J Clin Endocrinol Metab 1976; 42: 403.PubMedCrossRefGoogle Scholar
  44. 44.
    Knudtzon J, Aarskog D. Growth hormone deficiency associated with the ectrodactyly-ectodermal dysplasia-clefting syndrome and isolated absent septum pellucidum. Pediatrics 1987; 79: 410.PubMedGoogle Scholar
  45. 45.
    McKusick VA, ed. Mendelian inheritance in man. 7th ed. Baltimore: The Johns Hopkins University Press, 1986.Google Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • John A. PhillipsIII
    • 1
  1. 1.Vanderbilt University School of MedicineNashvilleUSA

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