scholarly journals Primary Growth Hormone (GH) Insensitivity and Insulin-Like Growth Factor Deficiency Caused by Novel Compound Heterozygous Mutations of the GH Receptor Gene: Genetic and Functional Studies of Simple and Compound Heterozygous States

2007 ◽  
Vol 92 (6) ◽  
pp. 2223-2231 ◽  
Author(s):  
Peng Fang ◽  
Stefan Riedl ◽  
Serge Amselem ◽  
Katherine L. Pratt ◽  
Brian M. Little ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Receptor Gene ◽  
Compound Heterozygous ◽  
Insulin Like Growth Factor ◽  
Functional Studies ◽  
Gh Receptor ◽  
Primary Growth ◽  
Factor Deficiency ◽  
Compound Heterozygous Mutations

scholarly journals Novel Compound Heterozygous Mutations of Growth Hormone (GH) Receptor Gene in a Patient with GH Insensitivity Syndrome1

1997 ◽  
Vol 82 (11) ◽  
pp. 3705-3709
Author(s):  
Hidesuke Kaji ◽  
Osamu Nose ◽  
Hitoshi Tajiri ◽  
Yutaka Takahashi ◽  
Keiji Iida ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Receptor Gene ◽  
Compound Heterozygous ◽  
Gh Receptor ◽  
Compound Heterozygous Mutations

scholarly journals Growth Hormone (GH) Receptor Isoform in Acromegaly: Lower Concentrations of GH but Not Insulin-Like Growth Factor-1 in Patients with a Genomic Deletion of Exon 3 in the GH Receptor Gene

2007 ◽  
Vol 53 (8) ◽  
pp. 1484-1488 ◽  
Author(s):  
Christoph Schmid ◽  
Pierre-Alexandre Krayenbuehl ◽  
René-Ludwig Bernays ◽  
Cornelia Zwimpfer ◽  
Friedrich E Maly ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Receptor Gene ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Insulin Like Growth Factor ◽  
Genomic Deletion ◽  
Gh Receptor ◽  
Study Participants ◽  
The Relationship

Abstract Background: A genomic deletion of exon 3 (d3-GHR) of the growth hormone (GH) receptor (GHR) has been linked to the effectiveness of GH therapy in children with GH deficiency. Carriers of the d3-GHR genotype had higher GH-induced growth rates than children homozygous for the full-length (fl)-GHR. The aim of this study was to test whether the relationship between GH and insulin-like growth factor-1 (IGF-1) concentrations is influenced by the GHR genotype in patients with acromegaly. Methods: Study participants were 44 adult patients with established diagnosis of acromegaly. The genotype of the GHR was determined in leukocyte DNA from peripheral blood. Clinical and biochemical findings at the time of diagnosis of acromegaly were obtained from the medical records of the patients. Results: fl-GHR homozygosity was found in 22 (50%) of patients, and 22 (50%) of patients had at least 1 d3 allele (d3-GHR). Demographic and clinical characteristics (age, height, weight, estimated duration of disease, and mean tumor size) of the 2 groups were comparable. Median (range) serum IGF-1 concentrations at the time of diagnosis were 670 (447–1443) μg/L in the fl-GHR group and 840 (342–1494) μg/L in the d3-GHR group (P = not significant). Basal GH concentrations were higher in the fl-GHR group [29.7 (3.8–159) μg/L] than in the d3-GHR group [8.4 (2.6–74 μg/L), P = 0.002], and so were mean (30.4 vs 6.1 μg/L, P = 0.005) and nadir (20.5 vs 5.1 μg/L, P = 0.003) GH concentrations during an oral glucose tolerance test. Conclusions: The GHR fl/d3 genotype modulates the relationship between GH and IGF-1 concentrations in patients presenting with acromegaly.

scholarly journals Dose-response effects of a new growth hormone receptor antagonist (B2036-PEG) on circulating, hepatic and renal expression of the growth hormone/insulin-like growth factor system in adult mice

2000 ◽  
Vol 167 (2) ◽  
pp. 295-303 ◽  
Author(s):  
JW van Neck ◽  
NF Dits ◽  
V Cingel ◽  
IA Hoppenbrouwers ◽  
SL Drop ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Receptor Antagonist ◽  
Growth Hormone Receptor ◽  
Binding Protein ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Gh Receptor ◽  
Igf I ◽  
Igfbp 3

The effects of growth hormone (GH) in regulating the expression of the hepatic and renal GH and insulin-like growth factor (IGF) system were studied by administering a novel GH receptor antagonist (GHRA) (B2036-PEG) at different doses (0, 1.25, 2.5, 5 and 10 mg/kg/day) to mice for 7 days. No differences were observed in the groups with respect to body weight, food consumption or blood glucose. However, a dose-dependent decrease was observed in circulating IGF-I levels and in hepatic and renal IGF-I levels at the highest doses. In contrast, in the 5 and 10 mg/kg/day GHRA groups, circulating and hepatic transcriptional IGF binding protein-3 (IGFBP-3) levels were not modified, likely resulting in a significantly decreased IGF-I/IGFBP-3 ratio. Hepatic GH receptor (GHR) and GH binding protein (GHBP) mRNA levels increased significantly in all GHRA dosage groups. Endogenous circulatory GH levels increased significantly in the 2.5 and 5 mg/kg/day GHRA groups. Remarkably, increased circulating IGFBP-4 and hepatic IGFBP-4 mRNA levels were observed in all GHRA administration groups. Renal GHR and GHBP mRNA levels were not modified by GHRA administration at the highest doses. Also, renal IGFBP-3 mRNA levels remained unchanged in most GHRA administration groups, whereas IGFBP-1, -4 and -5 mRNA levels were significantly increased in the 5 and 10 mg/kg/day GHRA administration groups. In conclusion, the effects of a specific GHR blockade on circulating, hepatic and renal GH/IGF axis reported here, may prove useful in the future clinical use of GHRAs.

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