This group of disorders includes disturbances of growth hormone action. Disturbances may occur on every level of growth hormone regulation from releasing hormone through growth hormone to the insulin like growth factor (IGF1). At each level either the hormone secretion itself or the receptor may be altered.
The interpretation of hormone levels follows the following general principle. Every defect in the signal cascade causes an upstream elevation of hormones while downstream the hormone levels are low.
Parameter | Interpretation |
---|---|
GHRH | Decreased with hypothalamic disturbances |
GH | Decreased with pituitary disturbances |
IGF1 | Decreased with disturbances further downstream |
TSH,LH,ACTH,FSH | Decreased with combined pituitary deficiency |
1. |
Lin SC et al. (1993) Molecular basis of the little mouse phenotype and implications for cell type-specific growth. |
2. |
Horan M et al. (2006) Genetic variation at the growth hormone (GH1) and growth hormone receptor (GHR) loci as a risk factor for hypertension and stroke. |
3. |
Geary MP et al. (2003) Sexual dimorphism in the growth hormone and insulin-like growth factor axis at birth. |
4. |
Rasmussen SK et al. (2000) Studies of the variability of the genes encoding the insulin-like growth factor I receptor and its ligand in relation to type 2 diabetes mellitus. |
5. |
Lambooij AC et al. (2003) Insulin-like growth factor-I and its receptor in neovascular age-related macular degeneration. |
6. |
Ueki K et al. (2006) Total insulin and IGF-I resistance in pancreatic beta cells causes overt diabetes. |
7. |
Liu JP et al. (1993) Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). |
8. |
Goddard AD et al. (1995) Mutations of the growth hormone receptor in children with idiopathic short stature. The Growth Hormone Insensitivity Study Group. |
9. |
Aleman A et al. (1999) Insulin-like growth factor-I and cognitive function in healthy older men. |
10. |
Sjögren 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. |
11. |
Yakar S et al. (1999) Normal growth and development in the absence of hepatic insulin-like growth factor I. |
13. |
Semsarian C et al. (1999) Skeletal muscle hypertrophy is mediated by a Ca2+-dependent calcineurin signalling pathway. |
14. |
Musarò A et al. (1999) IGF-1 induces skeletal myocyte hypertrophy through calcineurin in association with GATA-2 and NF-ATc1. |
15. |
Playford MP et al. (2000) Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta-catenin. |
16. |
Harman SM et al. (2000) Serum levels of insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-3, and prostate-specific antigen as predictors of clinical prostate cancer. |
17. |
Yanovski JA et al. (2000) Insulin-like growth factors and bone mineral density in African American and White girls. |
18. |
Le Roith D et al. (2001) What is the role of circulating IGF-I? |
19. |
Musarò A et al. (2001) Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle. |
20. |
Hellstrom A et al. (2001) Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: direct correlation with clinical retinopathy of prematurity. |
21. |
Smith PJ et al. (2002) An exonic splicing enhancer in human IGF-I pre-mRNA mediates recognition of alternative exon 5 by the serine-arginine protein splicing factor-2/alternative splicing factor. |
22. |
Barton ER et al. (2002) Muscle-specific expression of insulin-like growth factor I counters muscle decline in mdx mice. |
23. |
Vaessen N et al. (2002) Association between genetic variation in the gene for insulin-like growth factor-I and low birthweight. |
24. |
Arends N et al. (2002) Polymorphism in the IGF-I gene: clinical relevance for short children born small for gestational age (SGA). |
25. |
Humbert S et al. (2002) The IGF-1/Akt pathway is neuroprotective in Huntington's disease and involves Huntingtin phosphorylation by Akt. |
26. |
Simó R et al. (2002) Free insulin growth factor-I and vascular endothelial growth factor in the vitreous fluid of patients with proliferative diabetic retinopathy. |
27. |
Carro E et al. (2002) Serum insulin-like growth factor I regulates brain amyloid-beta levels. |
29. |
None (2003) Insulin-like growth factors and the basis of growth. |
30. |
Bonapace G et al. (2003) A novel mutation in a patient with insulin-like growth factor 1 (IGF1) deficiency. |
31. |
Sussenbach JS et al. (1992) Structure and expression of the human insulin-like growth factor genes. |
32. |
Usala AL et al. (1992) Brief report: treatment of insulin-resistant diabetic ketoacidosis with insulin-like growth factor I in an adolescent with insulin-dependent diabetes. |
33. |
Ruberte J et al. (2004) Increased ocular levels of IGF-1 in transgenic mice lead to diabetes-like eye disease. |
34. |
Walenkamp MJ et al. (2005) Homozygous and heterozygous expression of a novel insulin-like growth factor-I mutation. |
35. |
Kurosu H et al. (2005) Suppression of aging in mice by the hormone Klotho. |
36. |
Sutter NB et al. (2007) A single IGF1 allele is a major determinant of small size in dogs. |
37. |
Kim S et al. (2007) Insulin-like growth factor-1 regulates platelet activation through PI3-Kalpha isoform. |
38. |
None (2007) Insulin-like growth factor-1 potentiates platelet activation via the IRS/PI3Kalpha pathway. |
39. |
Johansson M et al. (2007) Implications for prostate cancer of insulin-like growth factor-I (IGF-I) genetic variation and circulating IGF-I levels. |
40. |
Kim SW et al. (1991) Structure and function of a human insulin-like growth factor-I gene promoter. |
42. |
Schoenle EJ et al. (1991) Recombinant human insulin-like growth factor I (rhIGF I) reduces hyperglycaemia in patients with extreme insulin resistance. |
43. |
Justice MJ et al. (1990) A genetic linkage map of mouse chromosome 10: localization of eighteen molecular markers using a single interspecific backcross. |
44. |
Taylor BA et al. (1991) Localization of the gene encoding insulin-like growth factor I on mouse chromosome 10. |
45. |
Pouladi MA et al. (2010) Full-length huntingtin levels modulate body weight by influencing insulin-like growth factor 1 expression. |
46. |
Mayack SR et al. (2010) Systemic signals regulate ageing and rejuvenation of blood stem cell niches. |
47. |
Takano K et al. (2010) Nebulin and N-WASP cooperate to cause IGF-1-induced sarcomeric actin filament formation. |
48. |
Bowcock A et al. (1990) Polymorphism and mapping of the IGF1 gene, and absence of association with stature among African Pygmies. |
49. |
Rapp R et al. (1988) Characterization of the protein which binds insulin-like growth factor in human serum. |
50. |
Guler HP et al. (1989) Small stature and insulin-like growth factors: prolonged treatment of mini-poodles with recombinant human insulin-like growth factor I. |
51. |
Le Bouc Y et al. (1986) Complete characterization of the human IGF-I nucleotide sequence isolated from a newly constructed adult liver cDNA library. |
52. |
Rotwein P et al. (1986) Organization and sequence of the human insulin-like growth factor I gene. Alternative RNA processing produces two insulin-like growth factor I precursor peptides. |
53. |
Höppener JW et al. (1985) The human gene encoding insulin-like growth factor I is located on chromosome 12. |
54. |
None (1986) Two insulin-like growth factor I messenger RNAs are expressed in human liver. |
55. |
Mathews LS et al. (1986) Regulation of insulin-like growth factor I gene expression by growth hormone. |
56. |
Morton CC et al. (1986) Human genes for insulin-like growth factors I and II and epidermal growth factor are located on 12q22--q24.1, 11p15, and 4q25--q27, respectively. |
57. |
Daughaday WH et al. (1972) Somatomedin: proposed designation for sulphation factor. |
58. |
Ullrich A et al. (1984) Isolation of the human insulin-like growth factor I gene using a single synthetic DNA probe. |
59. |
Rinderknecht E et al. (1978) The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. |
60. |
Jansen M et al. () Sequence of cDNA encoding human insulin-like growth factor I precursor. |
61. |
Brissenden JE et al. () Human chromosomal mapping of genes for insulin-like growth factors I and II and epidermal growth factor. |
62. |
Tricoli JV et al. () Localization of insulin-like growth factor genes to human chromosomes 11 and 12. |
63. |
Li CH et al. (1983) Total synthesis of insulin-like growth factor I (somatomedin C). |
64. |
Svoboda ME et al. (1980) Purification of somatomedin-C from human plasma: chemical and biological properties, partial sequence analysis, and relationship to other somatomedins. |
65. |
Copeland KC et al. (1980) Induction of immunoreactive somatomedin C human serum by growth hormone: dose-response relationships and effect on chromatographic profiles. |
66. |
Van Wyk JJ et al. (1980) Evidence from radioligand assays that somatomedin-C and insulin-like growth factor-I are similar to each other and different from other somatomedins. |
67. |
Powell-Braxton L et al. (1993) IGF-I is required for normal embryonic growth in mice. |
68. |
Baker J et al. (1993) Role of insulin-like growth factors in embryonic and postnatal growth. |
69. |
Woods KA et al. (1996) Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene. |
70. |
Lembo G et al. (1996) Elevated blood pressure and enhanced myocardial contractility in mice with severe IGF-1 deficiency. |
71. |
Zhu J et al. (1997) Analysis of a peptide hormone-receptor interaction in the yeast two-hybrid system. |
73. |
None (1998) Insulin-like growth factor-I and new opportunities for cancer prevention. |
74. |
Hankinson SE et al. (1998) Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. |
76. |
Goossens M et al. (1986) Isolated growth hormone (GH) deficiency type 1A associated with a double deletion in the human GH gene cluster. |
77. |
Greenhalgh CJ et al. (2005) SOCS2 negatively regulates growth hormone action in vitro and in vivo. |
78. |
Millar DS et al. (2003) Novel mutations of the growth hormone 1 (GH1) gene disclosed by modulation of the clinical selection criteria for individuals with short stature. |
79. |
Takahashi Y et al. (1996) Brief report: short stature caused by a mutant growth hormone. |
80. |
Mendlewicz J et al. (1999) Genetic control of 24-hour growth hormone secretion in man: a twin study. |
82. |
Hindmarsh PC et al. (1999) A sexually dimorphic pattern of growth hormone secretion in the elderly. |
83. |
Saitoh H et al. (1999) A Japanese family with autosomal dominant growth hormone deficiency. |
84. |
Kamijo T et al. (1999) Mutations in intron 3 of GH-1 gene associated with isolated GH deficiency type II in three Japanese families. |
85. |
Leiberman E et al. (2000) Short stature in carriers of recessive mutation causing familial isolated growth hormone deficiency. |
86. |
Abdul-Latif H et al. (2000) Growth hormone deficiency type IB caused by cryptic splicing of the GH-1 gene. |
87. |
Hasegawa Y et al. (2000) Identification of novel human GH-1 gene polymorphisms that are associated with growth hormone secretion and height. |
88. |
Moseley CT et al. (2002) An exon splice enhancer mutation causes autosomal dominant GH deficiency. |
89. |
Ho Y et al. (2002) A defined locus control region determinant links chromatin domain acetylation with long-range gene activation. |
90. |
Takahashi I et al. (2002) An exonic mutation of the GH-1 gene causing familial isolated growth hormone deficiency type II. |
92. |
Horan M et al. (2003) Human growth hormone 1 (GH1) gene expression: complex haplotype-dependent influence of polymorphic variation in the proximal promoter and locus control region. |
93. |
Ryther RC et al. (2003) Disruption of exon definition produces a dominant-negative growth hormone isoform that causes somatotroph death and IGHD II. |
94. |
Wolfrum C et al. (2003) Role of Foxa-2 in adipocyte metabolism and differentiation. |
95. |
Akinci A et al. (1992) Isolated growth hormone (GH) deficiency type IA associated with a 45-kilobase gene deletion within the human GH gene cluster. |
96. |
Lewis MD et al. (2004) A novel dysfunctional growth hormone variant (Ile179Met) exhibits a decreased ability to activate the extracellular signal-regulated kinase pathway. |
97. |
Dennison EM et al. (2004) Polymorphism in the growth hormone gene, weight in infancy, and adult bone mass. |
98. |
Mullis PE et al. (2005) Isolated autosomal dominant growth hormone deficiency: an evolving pituitary deficit? A multicenter follow-up study. |
99. |
Besson A et al. (2005) Short stature caused by a biologically inactive mutant growth hormone (GH-C53S). |
100. |
Mullis PE et al. (1992) Prevalence of human growth hormone-1 gene deletions among patients with isolated growth hormone deficiency from different populations. |
101. |
Vivenza D et al. (2006) A novel deletion in the GH1 gene including the IVS3 branch site responsible for autosomal dominant isolated growth hormone deficiency. |
102. |
Ho Y et al. (2006) Locus control region transcription plays an active role in long-range gene activation. |
103. |
Petkovic V et al. (2007) Evaluation of the biological activity of a growth hormone (GH) mutant (R77C) and its impact on GH responsiveness and stature. |
104. |
Ge G et al. (2007) Bone morphogenetic protein 1 processes prolactin to a 17-kDa antiangiogenic factor. |
105. |
Petkovic V et al. (2007) Exon splice enhancer mutation (GH-E32A) causes autosomal dominant growth hormone deficiency. |
106. |
Hess O et al. (2007) Variable phenotypes in familial isolated growth hormone deficiency caused by a G6664A mutation in the GH-1 gene. |
107. |
Giordano M et al. (2008) A functional common polymorphism in the vitamin D-responsive element of the GH1 promoter contributes to isolated growth hormone deficiency. |
108. |
Shariat N et al. (2008) Isolated growth hormone deficiency type II caused by a point mutation that alters both splice site strength and splicing enhancer function. |
109. |
He YA et al. (1990) A Chinese familial growth hormone deficiency with a deletion of 7.1 kb of DNA. |
110. |
Vnencak-Jones CL et al. (1990) Use of polymerase chain reaction in detection of growth hormone gene deletions. |
111. |
Chen EY et al. (1989) The human growth hormone locus: nucleotide sequence, biology, and evolution. |
112. |
Masuda N et al. (1988) Molecular cloning of cDNA encoding 20 kDa variant human growth hormone and the alternative splicing mechanism. |
113. |
Vnencak-Jones CL et al. (1988) Molecular basis of human growth hormone gene deletions. |
114. |
Fiddes JC et al. (1979) Structure of genes for human growth hormone and chorionic somatomammotropin. |
115. |
Braga S et al. (1986) Familial growth hormone deficiency resulting from a 7.6 kb deletion within the growth hormone gene cluster. |
116. |
Xu WM et al. (1988) Construction of a genetic map of human chromosome 17 by use of chromosome-mediated gene transfer. |
117. |
Morgan JR et al. (1987) Expression of an exogenous growth hormone gene by transplantable human epidermal cells. |
118. |
Martial JA et al. (1979) Human growth hormone: complementary DNA cloning and expression in bacteria. |
119. |
Cooke NE et al. (1986) The related genes encoding growth hormone and prolactin have been dispersed to chromosomes 10 and 17 in the rat. |
120. |
Niall HD et al. (1971) Sequences of pituitary and placental lactogenic and growth hormones: evolution from a primordial peptide by gene reduplication. |
121. |
Chakravarti A et al. (1984) Patterns of polymorphism and linkage disequilibrium suggest independent origins of the human growth hormone gene cluster. |
122. |
George DL et al. (1981) The genes for growth hormone and chorionic somatomammotropin are on the long arm of human chromosome 17 in region q21 to qter. |
123. |
Harper ME et al. (1982) Chromosomal localization of the human placental lactogen-growth hormone gene cluster to 17q22-24. |
124. |
Owerbach D et al. (1980) Genes for growth hormone, chorionic somatommammotropin, and growth hormones-like gene on chromosome 17 in humans. |
125. |
Sirand-Pugnet P et al. (1995) An intronic (A/U)GGG repeat enhances the splicing of an alternative intron of the chicken beta-tropomyosin pre-mRNA. |
126. |
Binder G et al. (1995) Screening for growth hormone (GH) gene splice-site mutations in sporadic cases with severe isolated GH deficiency using ectopic transcript analysis. |
127. |
Phillips JA et al. (1994) Genetic basis of endocrine disease. 6. Molecular basis of familial human growth hormone deficiency. |
128. |
Igarashi Y 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. |
129. |
Cogan JD et al. (1993) Heterogeneous growth hormone (GH) gene mutations in familial GH deficiency. |
130. |
Jones BK et al. (1995) The human growth hormone gene is regulated by a multicomponent locus control region. |
131. |
Cogan JD et al. (1995) A recurring dominant negative mutation causes autosomal dominant growth hormone deficiency--a clinical research center study. |
132. |
Binder G et al. (1996) Mechanisms responsible for dominant expression of human growth hormone gene mutations. |
133. |
Sundström M et al. (1996) Crystal structure of an antagonist mutant of human growth hormone, G120R, in complex with its receptor at 2.9 A resolution. |
134. |
Cogan JD et al. (1997) A novel mechanism of aberrant pre-mRNA splicing in humans. |
135. |
Smith LE et al. (1997) Essential role of growth hormone in ischemia-induced retinal neovascularization. |
136. |
Takahashi Y et al. (1997) Biologically inactive growth hormone caused by an amino acid substitution. |
137. |
Boguszewski CL et al. (1997) Increased proportion of circulating non-22-kilodalton growth hormone isoforms in short children: a possible mechanism for growth failure. |
138. |
Behncken SN et al. (1997) Aspartate 171 is the major primate-specific determinant of human growth hormone. Engineering porcine growth hormone to activate the human receptor. |
139. |
Gertner JM et al. (1998) Genetic defects in the control of growth hormone secretion. |
140. |
McCarthy EM et al. (1998) Characterization of an intron splice enhancer that regulates alternative splicing of human GH pre-mRNA. |