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Hormonelle Wachstumsstörungen

  • Roland Pfäffle
  • Oliver Blankenstein
Part of the Handbuch der Molekularen Medizin book series (HDBMOLEK, volume 7)

Zusammenfassung

Eine kindliche Wachstumsstörung kann das erste und z. T. auch das einzige Symptom einer Vielzahl von Krankheiten sein. Dementsprechend komplex gestaltet sich oft die Diagnostik eines pathologischen Wachstums bei einem Kind. Untersuchungen auf hormonelle Störungen bei einem Kleinwuchs stellen daher nur eine Facette in einem großen Spektrum diagnostischer Maßnahmen dar, die bei der Ursachensuche zur Anwendung gelangen. Chronisch entzündliche Darmerkrankungen wie der Morbus Crohn oder chronische Malabsorptions- und Malassimilationsyndrome (Zöliakie) sind typische Beispiele nicht hormoneller Erkrankungen, die in einem frühen Erkrankungsstadium oder bei milder Ausprßgung bei dem betroffenen Kind allein durch eine Wachstumsstörung auffallen können. Zudem reagieren sßmtliche Hormonregelkreise beim Kind sensibel auf das Vorliegen somatischer oder psychischer Störungen.

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Literatur

  1. Amselem S., Duquesnoy P., Attree O. et al. (1989) Laron dwarfism and mutations of the growth hormone-receptor gene. N Engl J Med 321:989–995PubMedGoogle Scholar
  2. Amselem S., Sobrier M.L., Duquesnoy P., Goossens M. (1991 a) Molecular Genetic of growth hormone resistance syndrome. Ann Endocrinol (Paris) 52:474–478Google Scholar
  3. Amselem S., Sobrier M.L., Duquesnoy P. et al. (1991 b) Recurrent nonsense mutations in the growth hormone receptor from patients with Laron dwarfism. J Clin Invest 87:1098–1102PubMedGoogle Scholar
  4. Asa S.L., Kovacs K. (1984) Functional morphology of the human fetal pituitary. Pathol Annu 19 Pt 1:275–315Google Scholar
  5. Asa S.L., Kovacs K., Laszlo F.A., Domokos I., Ezrin C. (1986) Human fetal adenohypophysis. Histologic and immunocytochemieal analysis. Neuroendocrinology 43:308–316PubMedGoogle Scholar
  6. Asa S.L., Kovacs K., Horvath E. et al. (1988) Human fetal adenohypophysis. Electron mieroscopic and ultrastructural immunocytochemical analysis. Neuroendocrinology 48:423–431PubMedGoogle Scholar
  7. Ayling R.M., Ross R., Towner P. et al. (1997) A dominant-negative mutation of the growth hormone receptor causes familial short stature. Nat Genet 16:13–14PubMedGoogle Scholar
  8. Bach I., Rhodes S.J., Pearse R.V.n. et al. (1995) P-Lim, a LIM homeodomain factor, is expressed during pituitary organ and cell commitment and synergizes with Pit-1. Proc Natl Acad Sci USA 92:2720–2724PubMedGoogle Scholar
  9. Backeljauw P.F., Underwood L.E. (1996) Prolonged treatment with recombinant insulin-like growth factor-I in children with growth hormone insensitivity syndrome-a clinical research center study. GHIS Collaborative Group. J Clin Endocrinol Metab 81:3312–3317PubMedGoogle Scholar
  10. Baker J., Liu J.P., Robertson E.J., Efstratiadis A. (1993) Role of insulin-like growth factors in embryonie and postnatal growth. Cell 75:73–82PubMedGoogle Scholar
  11. Bedford F.K., Christopherson K., Nachtigal M.W., Shen W.H., Julius D.J., Ingraham H.A. (1996) Molecular biology of pituitary development and disease. Horm Res 45:19–21PubMedGoogle Scholar
  12. Bennett L.I., Weinberger H., Escamilla R., Margen S., Li C.H., Evans H.M. (1950) Failure of hypohyseal growth hormone to produce nitrogen storage in a girl with hypohyseal dwarfism. J Clin Endocrinol 10:492–495Google Scholar
  13. Berg M.A., Argente J., Chernausek S. et al. (1993) Diverse growth hormone receptor gene mutations in Laron syndrome. Am J Hum Genet 52:998–1005PubMedGoogle Scholar
  14. Bertherat J., Bluet Pajot M.T., Epelbaum J. (1995) Neuroendocrine regulation of growth hormone. Eur J Endocrinol 132:12–24Google Scholar
  15. Binder G., Ranke M.B. (1995) Screening for growth hormone (GH) gene splice-site mutations in sporadie cases with severe isolated GH deficiency using ectopie transcript analysis. J Clin Endocrinol Metab 80:1247–1252PubMedGoogle Scholar
  16. Blankenstein O., Kim C., Heinze H., Schneider A., Kentrup H., Pfßffle R. (1999) Genetic analysis of the growth hormone releasing hormone receptor in patients with hypopituitarism (abstract). Horm Res [Suppl 2] 51:33Google Scholar
  17. Bluet-Pajot M.T., Epelbaum J., Gourdji D., Hammond C., Kordon C. (1998) Hypothalamic and hypophyseal regulation of growth hormone secretion. Cell Mol Neurobiol 18:101–123PubMedGoogle Scholar
  18. Blum W.F., Ranke M.B. (1990) Use of insulin-like growth factor-binding protein 3 for the evaluation of growth disorders. Horm Res [Suppl 4] 33:31–37PubMedGoogle Scholar
  19. Blum W.F., Albertsson-Wikland K., Rosberg S., Ranke M.B. (1993) Serum levels of insulin-like growth factor I (IGFI) and IGF bin ding protein 3 reflect spontaneous growth hormone secretion. J Clin Endocrinol Metab 76:1610–1616PubMedGoogle Scholar
  20. Bowers C.Y., Aister D.K., Frentz J.M. (1992) The growth hormone-releasing activity of a synthetie hexapeptide in normal men and short statured children after oral administration. J Clin Endocrinol Metab 74:292–298PubMedGoogle Scholar
  21. Braga S., Phillips J.A., Joss E., Schwarz H., Zuppinger K. (1986) Familial growth hormone deficiency resulting from a 7.6 kb deletion within the growth hormone gene cluster. Am J Med Genet 25:443–452PubMedGoogle Scholar
  22. Brown M.R., Parks J.S., Adess M.E. et al. (1998) Central hypothyroidism reveals compound heterozygous mutations in the Pit-1 gene. Horm Res 49:98–102PubMedGoogle Scholar
  23. Buckwalter M.S., Katz R.W., Camper S.A. (1991) Localization of the panhypopituitary dwarf mutation (df) on mouse chromosome 11 in an intersubspecific backcross. Genomics 10:515–526PubMedGoogle Scholar
  24. Carel J.C., Chaussain J.L., Chatelain P., Savage M.O. (1996) Growth hormone insensitivity syndrome (Laron syndrome): main characteristics and effects of IGFI treatment. Diabetes Metab 22:251–256PubMedGoogle Scholar
  25. Chen E.Y., Liao Y.C., Smith D.H., Barrera-Saldana H.A., Gelinas R.E., Seeburg P.H. (1989) The human growth hormone locus: nucleotide sequence, biology, and evolution. Genomics 4:479–497PubMedGoogle Scholar
  26. Chen R.G., Shen Y.N., Yei J. et al. (1993) A comparative study of growth hormone (GH) and GH-releasing hormone( 1-29)-NH2 for stimulation of growth in children with GH deficiency. Acta Paediatr Suppl 388:32–36PubMedGoogle Scholar
  27. Cogan J.D., Phillips J.A. 3rd (1998) Growth disorders caused by genetic defects in the growth hormone pathway. Adv Pediatr 45:337–361PubMedGoogle Scholar
  28. Cogan J.D., Phillips J.A. 3rd, Sakati N., Frisch H., Schober E., Milner R.D. (1993) Heterogeneous growth hormone (GH) gene mutations in familial GH deficiency. J Clin Endocrinol Metab 76:1224–1228Google Scholar
  29. Cogan J.D., Ramel B., Lehto M. et al. (1995) A recurring dominant negative mutation causes autosomal dominant growth hormone deficiency-a clinical research center study. J Clin Endocrinol Metab 80:3591–3595PubMedGoogle Scholar
  30. Cogan J.D., Prince M.A., Lekhakula S. et al. (1997) A novel mechanism of aberrant pre-mRNA splicing in humans. Hum Mol Genet 6:909–912PubMedGoogle Scholar
  31. Cogan J.D., Wu W., Phillips J.A. 3rd et al. (1998) The PROP1 2-base pair deletion is a common cause of combined pituitary hormone deficiency. J Clin Endocrinol Metab 83:3346–3349PubMedGoogle Scholar
  32. Cohen L.E., Wondisford F.E., Salvatoni A. et al. (1995) A „hot spot” in the Pit-1 gene responsible for combined pituitary hormone deficiency: clinical and molecular correlates. J Clin Endocrinol Metab 80:679–684PubMedGoogle Scholar
  33. Dattani M.T., Martinez-Barbera J.P., Thomas P.Q. et al. (1998) Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse. Nat Genet 19:125–133PubMedGoogle Scholar
  34. Dattani M., Brickmann J., Tyrrell R. et al. (1999) Novel mutations of Hesxl associated with septo-optic dysplasia in man (abstract). Horm Res [Suppl 2]51:32Google Scholar
  35. de Zegher F., Pernasetti F., Vanhole C., Devlieger H., Van den Berghe G., Martial J.A. (1995) The prenatal role of thyroid hormone evidenced by fetomaternal Pit-1 deficiency. J Clin Endocrinol Metab 80:3127–3l10PubMedGoogle Scholar
  36. DeAlmeida V.I., Mayo K.E. (1998) Identification of binding domains of the growth hormone-releasing hormone receptor by analysis of mutant and chimeric receptor proteins. Mol Endocrinol 12:750–765PubMedGoogle Scholar
  37. Dornene H., Krishnamurthi K., Eshet R. et al. (1993) Growth hormone (GH) stimulates insulin-like growth factor-I (IGF-I) and IGF-I-binding protein-3, but not GH receptor gene expression in livers of juvenile rats. Endocrinology 133:675–682Google Scholar
  38. Duquesnoy P., Sobrier M.L., Amselem S., Goossens M. (1991) Defective membrane expression of human growth hormone (GH) receptor causes Laron-type GH insensitivity syndrome. Proc Natl Acad Sci USA 88:10272–10276PubMedGoogle Scholar
  39. Edery M., Rozakis-Adcock M., Goujon L. et al. (1993) Lack of hormone binding in COS-7 cells expressing a mutated growth hormone receptor found in Laron dwarfism. J Clin Invest 91:838–844PubMedGoogle Scholar
  40. Feingold M., Shiere F., Fogeis H.R., Donaldson D. (1969) Rieger’s syndrome. Pediatrics 44:564–569PubMedGoogle Scholar
  41. Fluck C., Deladoey J., Rutishauser K. et al. (1998) Phenotypic variability in familial combined pituitary hormone deficiency caused by a PROP1 gene mutation resulting in the substitution of Arg->Cys at codon 120 (R120 C). J Clin Endocrinol Metab 83:3727–3734PubMedGoogle Scholar
  42. Fofanova O., Takamura N., Kinoshita E. et al. (1998) Compound heterozygous deletion of the PROP-1 gene in children with combined pituitary hormone deficiency. J Clin Endocrinol Metab 83:2601–2604PubMedGoogle Scholar
  43. Fox S.R., Jong M.T., Casanova J., Ye Z.S., Stanley F., Samuels H.H. (1990) The homeodomain protein, Pit-1/GHF-1, is capable of binding to and activating cell-specific elements of both the growth hormone and prolactin gene promoters. Mol Endocrinol 4:1069–1080PubMedGoogle Scholar
  44. Freyd G., Kim S.K., Horvitz H.R. (1990) Novel cysteine-rich motif and homeodomain in the product of the Caenorhabditis elegans cell lineage gene lin-11. Nature 344:876–879PubMedGoogle Scholar
  45. Gage P.J., Camper S.A. (1997) Pituitary homeobox 2, a novel member of the bicoid-related family of homeobox genes, is a potential regulator of anterior structure formation. Hum Mol Genet 6:457–464PubMedGoogle Scholar
  46. Gaylinn B.D., Harrison J.K., Zysk J.R., Lyons C.E., Lynch K.R., Thorner M.O. (1993) Molecular cloning and expression of a human anterior pituitary receptor for growth hormone-releasing hormone. Mol Endocrinol 7:77–84PubMedGoogle Scholar
  47. Gaylinn B.D., Kap Herr C von, Golden W.L., Thorner M.O. (1994) Assignment of the human growth hormone-releasing hormone receptor gene (GHRHR) to 7p14 by in situ hybridization. Genomics 19: 193–195PubMedGoogle Scholar
  48. Gehring W.J., Hiromi Y. (1986) Homeotic genes and the homeobox. Annu Rev Genet 20:147–173PubMedGoogle Scholar
  49. Gibbs C.J., Jr., Asher D.M., Brown P.W., Fradkin J.E., Gajdusek D.C. (1993) Creutzfeldt-Jakob disease infectivity of growth hormone derived from human pituitary glands. N Engl J Med 328:358–359PubMedGoogle Scholar
  50. Gluckman P.D., Harding J.E. (1997) The physiology and pathophysiology of intrauterine growth retardation. Horm Res [Suppl 1]48:11–16PubMedGoogle Scholar
  51. Goddard A.D., Covello R., Luoh S.M. et al. (1995) Mutations of the growth hormone receptor in children with idiopathic short stature. The Growth Hormone Insensitivity Study Group. N Engl J Med 333:1093–1098PubMedGoogle Scholar
  52. Godfrey P., Rahal J.O., Beamer W.G., Copeland N.G., Jenkins N.A., Mayo K.E. (1993) GHRH receptor of little mice contains amissense mutation in the extracellular domain that disrupts receptor function. Nat Genet 4:227–232PubMedGoogle Scholar
  53. Godowski P.J., Leung D.W., Meacham L.R. et al. (1989) Characterization of the human growth hormone receptor gene and demonstration of a partial gene deletion in two patients with Laron-type dwarfism. Proc Natl Acad Sci USA 86:8083–8087PubMedGoogle Scholar
  54. Goeddel D.V., Heyneker H.L., Hozumi T. et al. (1979) Direct expression in Escherichia coli of a DNA sequence coding for human growth hormone. Nature 281:544–548PubMedGoogle Scholar
  55. Hamilton J., Blaser S., Daneman D. (1998) MR imaging in idiopathic growth hormone deficiency. AJNR Am J Neuroradiol 19: 1609–1615PubMedGoogle Scholar
  56. Hauffa B.P., Illig R., Torresani T., Stolecke H., Phillips J.A.d. (1989) Discordant immune and growth response to pituitary and biosynthetic growth hormone in siblings with isolated growth hormone deficiency type IA. Acta Endocrinol (Copenh) 121:609–614Google Scholar
  57. He Y.A., Chen S.S., Wang Y.X., Lin X.Y., Wang D.F. (1990) A Chinese familial growth hormone deficiency with adeletion of 7.1 kb of DNA. J Med Genet 27:151–154PubMedGoogle Scholar
  58. Hermesz E., Mackern S., Mahon K.A. (1996) Rpx: a novel anterior-restricted homeobox gene progressively activated in the prechordal plate, anterior neural plate and Rathke’s pouch of the mouse embryo. Development 122:41–52PubMedGoogle Scholar
  59. Herr W., Sturm R.A., Clerc R.G. et al. (1988) The POU domain: a large conserved region in the mammalian pit-1, oct-1, oct-2, and Caenorhabditis elegans unc-86 gene products. Genes Dev 2:1513–1516PubMedGoogle Scholar
  60. Hintz R.L. (1992) Untoward events in patients treated with growth hormone in the USA. Horm Res 38:44–49PubMedGoogle Scholar
  61. Hintz R.L. (1995) The prismatic case of Creutzfeldt-Jakob disease associated with pituitary growth hormone treatment. J Clin Endocrinol Metab 80:2298–2301PubMedGoogle Scholar
  62. Hintz R.L., Rosenfeld R.G., Wilson D.M. et al. (1982) Biosynthetic methionyl human growth hormones is biologically active in adult man. Lancet 1:1276–1279PubMedGoogle Scholar
  63. Hirt H., Kirneiman J., Birnbaum M.J. et al. (1987) The human growth hormone gene locus: structure, evolution, and allelic variations. DNA 6:59–70PubMedGoogle Scholar
  64. Hoppener J.W., de Pagter-Holthuizen P., Geurts van Kessel AH et al. (1985) The human gene encoding insulin-like growth factor I is located on chromosome 12. Hum Genet 69:157–160PubMedGoogle Scholar
  65. Hummelink R., Sippell W.G., Benoit K.G., Danielson K., Faijerson Y. (1993) Intranasal administration of growth hormone-releasing hormone(1-29)-NH2 in children with growth hormone deficiency: effects on growth hormone secretion and growth. Acta PaediatrSuppl 388:23–27Google Scholar
  66. Igarashi Y., Ogawa M., Kamijo T. et al. (1993) A new mutation causing inherited growth hormone deficiency: a compound heterozygote of a 6.7 kb deletion and a two base deletion in the third exon of the GH-1 gene. Hum Mol Genet 2:1073–1074PubMedGoogle Scholar
  67. Ingraham H.A., Albert V.R., Chen R.P. et al. (1990a) A family of POU-domain and Pit1l tissue-specific transcription factors in pituitary and neuroendocrine development. Annu Rev Physiol 52:773–791PubMedGoogle Scholar
  68. Ingraham H.A., Chen R.P., Mangalam H.J. et al. (1988) A tissuespecific transcription factor containing a homeodomain specifies a pituitary phenotype. Cell 55:519–529PubMedGoogle Scholar
  69. Ingraham H.A., Flynn S.E., Voss J.W. et al. (1990b) The POUspecific domain of Pit-1 is essential for sequence-specific, high affinity DNA binding and DNA-dependent Pit-1-Pit-1 interactions. Cell 61:1021–1033PubMedGoogle Scholar
  70. Irie Y., Tatsumi K., Ogawa M. et al. (1995) A novel E250X mutation of the PIT1 gene in a patient with combined pituitary hormone deficiency. Endocr J 42:351–354PubMedGoogle Scholar
  71. Jacobson E.M., Li P., Rosenfeld M.G., Aggarwal A.K.(1996) Crystallization and preliminary X-ray analysis of Pit-1 POU domain complexed to a 28 base pair DNA element. Proteins 24:263–265PubMedGoogle Scholar
  72. Jacobson E.M., Li P., Leon-del-Rio A., Rosenfeld M.G., Aggarwal A.K. (1997) Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility. Genes Dev 11:198–212PubMedGoogle Scholar
  73. Jacquemin P., Alsat E., Oury C. et al. (1996) The enhancers of the human placental lactogen B, A, and L genes: progressive activation during in vitro trophoblast differentiation and importance of the DF-3 element in determining their respective activities. DNA Cell Biol 15:845–854PubMedGoogle Scholar
  74. Jones B.K., Monks B.R., Liebhaber S.A., Cooke N.E. (1995) The human growth hormone gene is regulated by a multi-component locus control region. Mol Cell Biol 15:7010–7021PubMedGoogle Scholar
  75. Kaji H., Nose O., Tajiri H. et al. (1997) Novel compound heterozygous mutations of growth hormone (GH) receptor gene in a patient with GH insensitivity syndrome. J Clin Endocrinol Metab 82:3705–3709PubMedGoogle Scholar
  76. Kamijo T., Phillips J.A.d. (1992) Detection of molecular heterogeneity in GH-1 gene deletions by analysis of polymerase chain reaction amplification products. J Clin Endocrinol Metab 74:786–789PubMedGoogle Scholar
  77. Kandemir N., Cila A., Besim A., Yordam N. (1998) Magnetic resonance imaging (MRI) findings in isolated growth hormone deficiency. Turk J Pediatr 40:385–392PubMedGoogle Scholar
  78. Karin M., Theill L., Castrillo J.L., McCormick A., Brady H. (1990) Cell type specific expression of the growth hormone gene and its control by GHF-1. Nippon Naibunpi Gakkai Zasshi 66:1205–1220PubMedGoogle Scholar
  79. Katakami H., Matsukura S. (1992) Regulation of growth hormone-releasing hormone gene expression and secretion. Nippon Naibunpi Gakkai Zasshi 68:1057–1072PubMedGoogle Scholar
  80. Kelly P.A., Goujon L., Sotiropoulos A. et al. (1994) The GH receptor and signal transduction. Horm Res 42:133–139PubMedGoogle Scholar
  81. Kirk J.M., Trainer P.J., Majrowski W.H., Murphy J., Savage M.O., Besser G.M. (1994) Treatment with GHRH(1-29)NH2 in children with idiopathic short stature induces a sustained increase in growth velocity. Clin Endocrinol (Oxf) 41:487–493Google Scholar
  82. Kowarski A.A., Schneider J., Ben-Galim E., Weldon V.V., Daughaday W.H. (1978) Growth failure with normal serum RIA-GH and low somatomedin activity: somatomedin restoration and growth acceleration after exogenous GH. J Clin Endocrinol Metab 47:461–464PubMedGoogle Scholar
  83. Kranzler J.H., Rosenbloom A.L., Martinez V., Guevara-Aguirre J. (1998) Normal intelligence with severe insulin-like growth factor I deficiency due to growth hormone receptor deficiency: a controlled study in a genetically homogeneous population. J Clin Endocrinol Metab 83:1953–1958PubMedGoogle Scholar
  84. Lacey K.A., Parkin J.M. (1974) Causes of short stature. A community study of children in Newcastle upon Tyne. Lancet 1:42–45PubMedGoogle Scholar
  85. Lajara R., Galgani J.P., Jr., Dempsher D.P., Bier D.M., Rotwein P. (1990) Low prevalence of insulin-like growth factor-I gene mutations in human growth disorders. J Clin Endocrinol Metab 70:687–692PubMedGoogle Scholar
  86. Lanes R., Carrillo E. (1994) Long-term therapy with a single daily subcutaneous dose of growth hormone releasing hormone (1-29) in prepubertal growth hormone deficient children. Venezuelan Collaborative Study Group. J Pediatr Endocrinol 7:303–308PubMedGoogle Scholar
  87. Laron Z. (1974) Syndrome of familial dwarfism and high plasma immunoreactive growth hormone. Isr J Med Sci 10:1247–1253PubMedGoogle Scholar
  88. Laron Z., Pertzelan A., Mannheimer S. (1966) Genetic pituitary dwarfism with high serum concentation of growth hormone-a new inborn error of metabolism? Isr J Med Sci 2:152–155PubMedGoogle Scholar
  89. Leidy J.W., Jr., Cugini C.D., Jr., Driscoll H.K., Chertow B.S. (1995) Time course of hypothalamic growth hormone-releasing hormone and somatostatin content in streptozoein diabetic rats: evidence for early changes in hypothalamic regulation. Brain Res 681:84–90PubMedGoogle Scholar
  90. Lemaigre F.P., Courtois S.J., Durviaux S.M., Egan C.J., LaFontaine D.A., Rousseau G.G. (1989a) Analysis of cis-and trans-acting elements in the hormone-sensitive human somatotropin gene promoter. J Steroid Biochem 34:79–83PubMedGoogle Scholar
  91. Lemaigre F.P., Courtois S.J., Lafontaine D.A., Rousseau G.G. (1989b) Evidence that the upstream stimulatory factor and the Sp1 transcription factor bind in vitro to the promoter of the human-growth-hormone gene. Eur J Biochem 181:555–561PubMedGoogle Scholar
  92. Leung D.W., Spencer S.A., Cachianes G. et al. (1987) Growth hormone receptor and serum binding protein: purification, cloning and expression. Nature 330:537–543PubMedGoogle Scholar
  93. Li S., Crenshaw E.B.d., Rawson E.J., Simmons D.M., Swanson L.W., Rosenfeld M.G. (1990) Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-1. Nature 347:528–533PubMedGoogle Scholar
  94. Lifshitz F., Lanes R., Pugliese M. et al. (1992) Sustained improvement in growth veloeity and recovery from suboptimal growth hormone (GH) secretion after treatment with human pituitary GH-releasing hormone-(1-44)-NH2. J Clin Endocrinol Metab 75:1255–1260PubMedGoogle Scholar
  95. Lin S.C., Lin C.R., Gukovsky I., Lusis A.J., Sawchenko P.E., Rosenfeld M.G. (1993) Molecular basis of the little mouse phenotype and implications for cell type-specific growth. Nature 364:208–213PubMedGoogle Scholar
  96. Ling N., Zeytin F., Bohlen P. et al. (1985) Growth hormone releasing factors. Annu Rev Biochem 54:403–423PubMedGoogle Scholar
  97. Lomasney J.W., Allen L.F., Lefkowitz R.J. (1995) Cloning and regulation of catecholamine receptor genes. In: Weintraub B.D. (ed) Molecular endocrinology. Raven Press, New York, pp 115–131Google Scholar
  98. Magalhaes A.C., Uehara K.C., Iezzi D. et al. (1995) MRI of congenital pituitary insufficiency. Rev Hosp Clin Fac Med Sao Paulo 50:182–184PubMedGoogle Scholar
  99. Maheshwari H.G., Silverman B.L., Dupuis J., Baumann G. (1998) Phenotype and genetic analysis of a syndrome caused by an inactivating mutation in the growth hormone-releasing hormone receptor: dwarfism of Sindh. J Clin Endocrinol Metab 83:4065–4074PubMedGoogle Scholar
  100. Mangalam H.J., Albert V.R., Ingraham H.A. et al. (1989) A pituitary POU domain protein, Pit-1, activates both growth hormone and prolactin promoters transcriptionally. Genes Dev 3:946–958PubMedGoogle Scholar
  101. Masuda N., Watahiki M., Tanaka M. et al. (1988) Molecular cloning of cDNA encoding 20 kDa variant human growth hormone and the alternative splicing mechanism. Biochim Biophys Acta 949:125–131PubMedGoogle Scholar
  102. Mayo K.E., Cerelli G.M., Lebo R.V., Bruce B.D., Rosenfeld M.G., Evans R.M. (1985) Gene encoding human growth hormone-releasing factor precursor:structure, sequence, and chromosomal assignment. Proc Natl Acad Sci USA 82:63–67PubMedGoogle Scholar
  103. Mayo K.E., Miller T.L., DeAlmeida V., Zheng J., Godfrey P.A. (1996) The growth-hormone-releasing hormone receptor: signal transduction, gene expression, and physiological function in growth regulation. Ann NY Acad Sci 805: 184–203PubMedGoogle Scholar
  104. Mitrakou A., Hadjidakis G., Raptis S., Bartsocas C.S., Souvatzoglou A. (1985) Heterogeneity of growth-hormone deficiency. Lancet 1:399–400PubMedGoogle Scholar
  105. Muceielli M.L., Martinez S., Pattyn A., Goridis C., Brunet J.F. (1996) Ot1x2, an Otx-related homeobox gene expressed in the pituitary gland and in a restricted pattern in the forebrain. Mol cell Neurosci 8:258–271Google Scholar
  106. Mullis P., Patel M., Brickell P.M., Brook C.G. (1990) Isolated growth hormone deficiency: analysis of the growth hormone (GH)-releasing hormone gene and the GH gene cluster. J Clin Endocrinol Metab 70:187–191PubMedGoogle Scholar
  107. Mullis P.E., Akinei A., Kanaka C., Eble A., Brook C.G. (1992) Prevalence of human growth hormone-1 gene deletions among patients with isolated growth hormone deficiency from different populations. Pediatr Res 31:532–534PubMedGoogle Scholar
  108. Musaro A., McCullagh K.J., Naya F.J., Olson E.N., Rosenthai N. (1999) IGF-1 induces skeletal myocyte hypertrophy through caleineurin in association with GATA-2 and NFATc1. Nature 400:581–585PubMedGoogle Scholar
  109. Netchine I., Talon P., Dastot F., Vitaux F., Goossens M., Amselern S. (1998) Extensive phenotypic analysis of a family with growth hormone (GH) deficiency caused by a mutation in the GH-releasing hormone receptor gene. J Clin Endocrinol Metab 83:432–436PubMedGoogle Scholar
  110. Neyzi O, Yordam N., Ocal G. et al. (1993) Growth response to growth hormone-releasing hormone(1-29)-NH2 compared with growth hormone. Acta Paediatr Suppl 388:16–22PubMedGoogle Scholar
  111. Nishi Y., Hamamoto K., Kajiyama M. et al. (1993) Treatment of isolated growth hormone deficiency type IA due to GH-I gene deletion with recombinant human insulin-like growth factor I. Acta Paediatr 82:983–986PubMedGoogle Scholar
  112. Ohta K., Nobukuni Y., Mitsubuchi H. et al. (I992a) Mutations in the Pit-1 gene in children with combined pituitary hormone deficiency. Biochem Biophys Res Commun 189:851–855Google Scholar
  113. Ohta K., Nobukuni Y., Mitsubuchi H. et al. (I992b) Characterization of the gene encoding human pituitary-specific transcription factor, Pit-1. Gene 122:387–388Google Scholar
  114. Parks J.S., Tenore A., Bongiovanni A.M., Kirkland R.T. (1978) Familial hypopituitarism with large sella turcica. N Engl J Med 298:698–702PubMedGoogle Scholar
  115. Parks J.S., Adess M.E., Brown M.R. (1997) Genes regulating hypothalamic and pituitary development. Acta Paediatr Suppl 423:28–32Google Scholar
  116. Pellegrini-Bouiller I., Belicar P., Barlier A. et al. (1996) A new mutation of the gene encoding the transcription factor Pit-1 is responsible for combined pituitary hormone deficiency. J Clin Endocrinol Metab 81:2790–2796PubMedGoogle Scholar
  117. Perez Jurado L.A., Phillips J.A.r., Francke U. (1994a) Exclusion of growth hormone (GH)-releasing hormone gene mutations in familial isolated GH deficiency by linkage and single strand conformation analysis. J Clin Endocrinol Metab 78:622–628Google Scholar
  118. Perez Jurado L.A., Phillips J.A.r., Summar M.L. et al. (1994b) Genetic mapping of the human growth hormone-releasing factor gene (GHRF) using two intragenic polymorphisms detected by PCR amplification. Genomics 20:132–134Google Scholar
  119. Petersenn S., Rasch A.C., Heyens M., Schulte H.M. (1998) Structure and regulation of the human growth hormone-releasing hormone receptor gene. Mol Endocrinol 12:233–247PubMedGoogle Scholar
  120. Pfßffle R.W., DiMattia G.E., Parks J.S. et al. (1992) Mutation of the POU-specific domain of Pit-1 and hypopituitarism without pituitary hypoplasia. Science 257:1118–1121Google Scholar
  121. Pfßffle R.W., Parks J.S., Brown M.R., Heimann G. (1993) Pit-1 and pituitary function. J Pediatr Endocrinol 6:229–233Google Scholar
  122. Pfßffle R.W., Kim C., Otten B. et al. (1996) Pit-1: clinical aspects. Horm Res 45:25–28Google Scholar
  123. Pfßffle R.W., Martinez R., Kim C. et al. (1997) GH and TSH deficiency. Exp Clin Endocrinol Diabetes [Suppl 4] 105:1–5Google Scholar
  124. Pfßffle R.W., Kim C., Wüller S. et al. (1998) Two Prop-1 mutations are prevalent among patients with combined pituitary hormone deficiency. Horm Res [Suppl 3] 50:10Google Scholar
  125. Phillips J.A. (1995) Inherited defects in growth hormone synthesis and action. In: Scriver C.R., Beaudet A.L., Sly W.S., Valle D. (eds) The metabolie basis of inherited disease. McGraw-Hill, New York, pp 3023–3044Google Scholar
  126. Phillips J.A.r., Cogan J.D. (1994) Genetic basis of endocrine disease. 6. Molecular basis of familial human growth hormone deficiency. J Clin Endocrinol Metab 78:11–16PubMedGoogle Scholar
  127. Procter A.M., Phillips J.A., 3rd, Cooper D.N. (1998) The molecular Genetics of growth hormone deficiency. Hum Genet 103:255–272PubMedGoogle Scholar
  128. Raben M.S. (1958) Treatment of a pituitary dwarf with human growth hormone. J Clin Endocrinol Metab 18:901–903PubMedGoogle Scholar
  129. Radoviek S., Nations M., Du Y., Berg L.A., Weintraub B.D., Wondisford F.E. (1992) A mutation in the POU-homeodomain of Pit-1 responsible for combined pituitary hormone deficiency. Science 257:1115–1118Google Scholar
  130. Raiti S. (1986) The national hormone and pituitary program (NHPP) historieal perspective. Acta Endocrinol Suppl 279:66–70Google Scholar
  131. Ranke M.B. (1996) Growth hormone stimulation tests. In: Ranke M.B. (ed) Diagnosties of endocrine function in children and adolescents. J&#amp;J im Barth, Mannheim Heidelberg Leipzig, pp 134–148Google Scholar
  132. Ranke M.B., Dowie J. (1999) KIGS and KIMS as tools for evidence-based medicine. Horm Res 51:83–86PubMedGoogle Scholar
  133. Ranke M.B., Wilton P. (1994) Adverse events during treatment with recombinant insulin-like growth factor I in patients with growth hormone insensitivity. Acta Paediatr Suppl 399:143–145PubMedGoogle Scholar
  134. Rao V.V., Loftler C., Schnittger S., Hansmann I. (1991) The gene for human growth hormone-releasing factor (GHRF) maps to or near chromosome 20p12. Cytogenet Ceil Genet 57:39–40Google Scholar
  135. Rinderknecht E., Humbel R.E. (1978a) The amino acid sequence of human insulin-like growth factor land its structural homology with proinsulin. J Biol Chem 253:2769–2776PubMedGoogle Scholar
  136. Rinderknecht E., Humbel R.E. (1978b) Primary structure of human insulin-like growth factor II. FEBS Lett 89:283–286PubMedGoogle Scholar
  137. Rogers P.C., Komp D., Rogol A., Sabio H. (1977) Possible effects of growth hormone on development of acute lymphoblastic leukaemia. Lancet 2:434–435PubMedGoogle Scholar
  138. Rona R.J., Tanner J.M. (1977) Aetiology of idiopathic growth hormone deficiency in England and Wales. Arch Dis Child 52:197–208PubMedGoogle Scholar
  139. Rosenbloom A.L., Guevara Aguirre J., Rosenfeld R.G., Fielder P.J. (1990) The little women of Loja-growth hormone-receptor deficiency in an inbred population of southern Ecuador. N Engl J Med 323:1367–1374Google Scholar
  140. Rosenbloom A.L., Guevara-Aguirre J., Berg M.A., Francke U. (1998) Stature in Ecuadorians heterozygous for growth hormone receptor gene E180 spliee mutation does not differ from that of homozygous normal relatives. J Clin Endocrinol Metab 83:2373–2375PubMedGoogle Scholar
  141. Rosenbloom A.L., Almonte A.S., Brown M.R., Fisher D.A., Baumbach L., Parks J.S. (1999) Clinical and biochemieal phenotype of familial anterior hypopituitarism from mutation of the PROP1 gene. J Clin Endocrinol Metab 84:50–57PubMedGoogle Scholar
  142. Rosenfeld R.G. (1997) Is growth hormone deficiency a viable diagnosis? J Clin Endocrinol Metab 82:349–351PubMedGoogle Scholar
  143. Rosenfeld R.G., Wilson D.M., Dollar L.A., Bennett A., Hintz R.L. (1982) Both human pituitary growth hormone and recombinant DNA-derived human growth hormone cause insulin resistance at a postreceptor site. J Clin Endocrinol Metab 54:1033–1038PubMedGoogle Scholar
  144. Sadeghi-Nejad A., Senior B. (1974) Autosomal dominant transmission of isolated growth hormone deficiency in iris-dental dysplasia (Rieger’s syndrome). J Pediatr 85:644–648PubMedGoogle Scholar
  145. Salmon W.D., Daughaday W.H. (1957) Hormonally controHed serum factor whieh stimulates sulfate incorporation by cartilage in vitro. J Lab Clin Med 49:825PubMedGoogle Scholar
  146. Salvatori R., Hayashida C.Y., Aguiar-Oliveira M.H. et al. (1999) Familial dwarfism due to a novel mutation of the growth hormone-releasing hormone receptor gene. J Clin Endocrinol Metab 84:917–923PubMedGoogle Scholar
  147. Sanchez J.E., Perera E., Baumbach L., Cleveland W.W. (1998) Growth hormone receptor mutations in children with idiopathie short stature. J Clin Endocrinol Metab 83: 4079–4083PubMedGoogle Scholar
  148. Savage M.O., Korbonits M., Grossman A.B. (1996) Clinical value of neuropeptides GHRH and GHRP. Arch Pediatr 3:148s–150sPubMedGoogle Scholar
  149. Schneid H., Seurin D., Le Bouc Y. (1991) Pathology of the growth and abnormalities of IGF genes. Ann Endocrinol 52:479–482Google Scholar
  150. Semina E.V., Reiter R., Leysens N.J. et al. (1996) Cloning and characterization of a novel bieoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome. Nat Genet 14:392–399PubMedGoogle Scholar
  151. Semina E.V., Reiter R.S., Murray J.C. (1997) Isolation of a new homeobox gene belonging to the Pitx/Rieg family: expression during lens development and mapping to the aphakia region on mouse chromosome 19. Hum Mol Genet 6:2109–2116PubMedGoogle Scholar
  152. Sheng H.Z., Zhadanov A.B., Mosinger B., Jr. et al. (1996) Specification of pituitary ceil lineages by the LIM homeobox gene Lhx3. Science 272:1004–1007PubMedGoogle Scholar
  153. Simmons D.M., Voss J.W., Ingraham H.A. et al. (1990) Pituitary cell phenotypes involve ceil-specific Pit-1 mRNA translation and synergistic interactions with other classes of transcription factors. Genes Dev 4:695–711PubMedGoogle Scholar
  154. Simon P., Decoster C., Brocas H., Schwers J., Vassart G. (1986) Absence of human chorionie somatomammotropin during pregnancy associated with two types of gene deletion. Hum Genet 74:235–238PubMedGoogle Scholar
  155. Sjogren K., Liu J.L., Blad K. et al. (1999) Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice. Proc Natl Acad Sci USA 96:7088–7092PubMedGoogle Scholar
  156. Sornson M.W., Wu W., Dasen J.S. et al. (1996) Pituitary lineage determination by the Prophet of Pit-1 homeodomain factor defective in Ames dwarfism. Nature 384:327–333PubMedGoogle Scholar
  157. Spencer S.A., Hammonds R.G., Henzel W.J., Rodriguez H., Waters M.J., Wood W.I. (1988) Rabbit liver growth hormone receptor and serum binding protein. Purification, characterization, and sequence. J Biol Chem 263:7862–7867PubMedGoogle Scholar
  158. Stahnke N. (1992) Leukemia in growth-hormone-treated patients: an update, 1992. Horm Res 38:56–62PubMedGoogle Scholar
  159. Stahnke N., Zeisel H.J. (1989) Growth hormone therapy and leukaemia. Eur J Pediatr 148:591–596PubMedGoogle Scholar
  160. StaHings-Mann M.L., Ludwiczak R.L., Klinger K.W., Rottman F. (1996) Alternative splicing of exon 3 of the human growth hormone receptor is the result of an unusual genetic polymorphism. Proc Natl Acad Sci USA 93:12394–12399Google Scholar
  161. Steendijk R. (1980) Diagnostic and aetiologic features of idiopathic and symptomatic growth hormone deficiency in the Netherlands. A survey of 176 children. Helv Paediatr Acta 35:129–139PubMedGoogle Scholar
  162. Steinfelder H.J., Hauser P., Nakayama Y. et al. (1991) Thyrotropin-releasing hormone regulation of human TSHB expression: role of a pituitary-specific transcription factor (Pit-1/GHF-1) and potential interaction with a thyroid hormone-inhibitory element. Proc Natl Acad Sci USA 88:3130–3134PubMedGoogle Scholar
  163. Steinfelder H.J., Radovick S., Mroczynski M.A. et al. (1992) Role of a pituitary-specific transcription factor (pit-1/GHF-1) or a closely related protein in cAMP regulation of human thyrotropin-beta subunit gene expression. J Clin Invest 89:409–419PubMedGoogle Scholar
  164. Sussenbach J.S. (1989) The gene structure of the insulin-like growth factor family. Prog Growth Factor Res 1:33–48PubMedGoogle Scholar
  165. Takahashi Y., Kaji H., Okimura Y., Goji K., Abe H., Chihara K. (1996) Brief report: short stature caused by a mutant growth hormone. N Engl J Med 334:432–436PubMedGoogle Scholar
  166. Takahashi Y., Shirono H., Arisaka O. et al. (1997) Biologically inactive growth hormone caused by an amino acid substitution. J Clin Invest 100: 1159–1165PubMedGoogle Scholar
  167. Tatsumi K., Miyai K., Notomi T. et al. (1992) Cretinism with combined hormone deficiency caused by a mutation in the PIT1 gene. Nat Genet 1:56–58PubMedGoogle Scholar
  168. Thomas P., Beddington R. (1996) Anterior primitive endoderm may be responsible for patterning the anterior neural plate in the mouse embryo. Curr Biol 6:1487–1496PubMedGoogle Scholar
  169. Thorner M.O., Vance M.L., Horvath E., Kovacs K. (1992) The anterior pituitary. In: Wilson J.D., Foster D.W. (eds) Textbook of endocrinology. Saunders, Philadelphia, pp 201–310Google Scholar
  170. Thorner M., Rochiccioli P., Colle M. et al. (1996) Once daily subcutaneous growth hormone-releasing hormone therapy accelerates growth in growth hormone-deficient children during the first year of therapy. Geref International Study Group. J Clin Endocrinol Metab 81:1189–1196PubMedGoogle Scholar
  171. Tillmann V., Buckler J.M., Kibirige M.S. et al. (1997) Biochemical tests in the diagnosis of childhood growth hormone deficiency. J Clin Endocrinol Metab 82:531–535PubMedGoogle Scholar
  172. Treisman J., Harris E., Desplan C. (1991) The paired box encodes a second DNA-binding domain in the paired homeo domain protein. Genes Dev 5:594–604PubMedGoogle Scholar
  173. Underwood L.E., Voina S.J., Van Wyk J.J. (1974) Restoration of growth by human growth hormone in hypopituitary dwarfs immunized by other human growth hormone preparations: clinical and immunological studies. J Clin Endocrinol Metab 38:288–297PubMedGoogle Scholar
  174. Valenta L.J., Sigel M.B., Lesniak M.A. et al. (1985) Pituitary dwarfism in a patient with circulating abnormal growth hormone polymers. N Engl J Med 312:214–217PubMedGoogle Scholar
  175. Vimpani G.V., Vimpani A.F., Lidgard G.P., Cameron E.H., Farquhar J.W. (1977) Prevalence of severe growth hormone deficiency. BMJ 2:427–430PubMedGoogle Scholar
  176. Vnencak-Jones C.L., Phillips J.A.d., Chen E.Y., Seeburg P.H. (1988) Molecular basis of human growth hormone gene deletions. Proc Natl Acad Sci USA 85:5615–5619PubMedGoogle Scholar
  177. Wagner J.K., Eble A., Hindmarsh P.C., Mullis P.E. (1998) Prevalence of human GH-l gene alterations in patients with isolated growth hormone deficiency. Pediatr Res 43:105–110PubMedGoogle Scholar
  178. Wajnrajch M.P., Gertner J.M., Harbison M.D., Chua S.C., Jr., Leibel R.L. (1996) Nonsense mutation in the human growth hormone-releasing hormone receptor causes growth failure analogous to the little (lit) mouse. Nat Genet 12:88–90PubMedGoogle Scholar
  179. Walker J.L., Crock P.A., Behncken S.N. et al. (1998) A novel mutation affecting the interdomain link region of the growth hormone receptor in a Vietnamese girl, and response to long-term treatment with recombinant human insulin-like growth factor-I and luteinizing hormone-releasing hormone analogue. J Clin Endocrinol Metab 83: 2554–2561PubMedGoogle Scholar
  180. Ward L., Chavez M., Huot C. et al. (1998) Severe congenital hypopituitarism with low prolactin levels and age-dependent anterior pituitary hypoplasia: a clue to a PIT-1 mutation. J Pediatr 132:1036–1038PubMedGoogle Scholar
  181. Way J.C., Chalfie M. (1988) Mec-3, a homeobox-containing gene that specifies differentiation of the touch receptor neurons in C. elegans. Cell 54:5–16PubMedGoogle Scholar
  182. Wilton P., Wallstrom A. (1991) An overview of the diagnoses in the Kabi Pharmacia International Growth Study. Acta Paediatr Suppl 379:93–98Google Scholar
  183. Wojcik J., Berg M.A., Esposito N. et al. (1998) Four contiguous amino acid substitutions, identified in patients with Laron syndrome, differently affect the binding affinity and intracellular trafficking of the growth hormone receptor. J Clin Endocrinol Metab 83:4481–4489PubMedGoogle Scholar
  184. Woods K.A., Camacho-Hubner C., Savage M.O., Clark A.J. (1996) Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene. N Engl J Med 335:1363–1367PubMedGoogle Scholar
  185. Woods K.A., Dastot F., Preece M.A. et al. (1997) Phenotype: genotype relationships in growth hormone insensitivity syndrome. J Clin Endocrinol Metab 82:3529–3535PubMedGoogle Scholar
  186. Wu W., Cogan J.D., Pfaffle R.W. et al. (1998) Mutations in PROP1 cause familial combined pituitary hormone deficiency. Nat Genet 18:147–149PubMedGoogle Scholar
  187. Wurzel J.M., Parks J.S., Herd J.E., Nielsen P.V. (1982) A gene deletion is responsible for absence of human chorionic somatomammotropin. DNA 1:251–257PubMedGoogle Scholar
  188. Youlton R. (1994) Growth hormone gene deletion: results of treatment with recombinant human insulin-like growth factor I. Acta Paediatr Suppl 399:150–151PubMedGoogle Scholar
  189. Zhadanov A.B., Bertuzzi S., Taira M., Dawid I.B., Westphal H. (1995a) Expression pattern of the murine LIM dass homeobox gene Lhx3 in subsets of neural and neuroendocrine tissues. Dev Dyn 202:354–364PubMedGoogle Scholar
  190. Zhadanov A.B., Copeland N.G., Gilbert D.J., Jenkins N.A., Westphal H. (1995 b) Genomic structure and chromosomal localization of the mouse LIM/homeobox gene Lhx3. Genomics 27:27–32PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2000

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  • Roland Pfäffle
  • Oliver Blankenstein

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