| 1. |
- Barbosa, Edna J L, 1961, et al.
(författare)
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Influence of the Exon 3-deleted/full-length Growth Hormone Receptor Polymorphism on the Response to Growth Hormone Replacement Therapy in Adults with Severe Growth Hormone Deficiency. : d3-GHR isoform in GHD adults
- 2009
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 94:2, s. 639-644
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Tidskriftsartikel (refereegranskat)abstract
- Context: There is considerable individual variation in the clinical response to growth hormone (GH) replacement therapy in GH deficient (GHD) adults. Useful predictors of treatment response are lacking. Objective: To assess the influence of the exon 3-deleted (d3-GHR) and full-length (fl-GHR) GH receptor isoforms on the response to GH replacement therapy in adults with severe GHD. Design, Patients: 124 adult GHD patients (79 men, median age 50 years) were studied before and after 12 months of GH therapy. GHD patients were divided into those bearing fl/fl alleles (Group 1) and those bearing at least one d3-GHR allele (Group 2), and the genotype was related to the effects of GH therapy on IGF-I levels and total body fat (BF). Intervention: GH dose was individually titrated to obtain normal serum IGF-I levels. Main Outcome Measures: GHR genotype was determined by PCR amplification, IGF-I levels by immunoassay, and BF by a four-compartment model. Results: Seventy-two (58%) patients had fl/fl genotype and were classified as Group 1, while 52 (42%) had at least one d3-GHR allele and were classified as Group 2 (40 were heterozygous and 12 were homozygous). At baseline, there were no significant differences in the study groups. Changes in IGF-I and BF after 12 months of GH treatment did not differ significantly between the two genotype groups. Conclusion: The presence of d3-GHR allele did not influence the response to GH replacement therapy in our cohort of adults with severe GHD.
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| 2. |
- Boguszewski, M. C., et al.
(författare)
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Insulin-like growth factor-1, leptin, body composition, and clinical status interactions in children with cystic fibrosis
- 2007
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Ingår i: Horm Res. - : S. Karger AG. - 0301-0163. ; 67:5, s. 250-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: Children with cystic fibrosis (CF) are of increased risk of reduced fat body mass (FBM) and lean body mass (LBM). Serum concentrations of insulin-like growth factor-1 (IGF-1)and leptin could be markers of LBM and/or FBM depletion. To evaluate the relationships between disease activity, body composition, IGF-1 and leptin concentrations in CF children. METHODS: A cross-sectional study with 26 CF children aged 5.0-15.5 years and 33 healthy controls, mean age 9.4 years. Body composition was evaluated by dual-energy X-ray absorptiometry. Fasting blood samples were analyzed for leptin, IGF-1 and IGFBP-3. RESULTS: FBM standard deviation score (SDS; CF boys -0.02 +/- 0.88 vs. 0.78 +/- 0.65, p < 0.01; CF girls -0.37 +/- 1.15 vs. 0.70 +/- 0.97, p < 0.05), leptin concentration (CF boys 2.07 +/- 0.79 vs. 3.07 +/- 1.28 ng/ml, p < 0.05; CF girls 2.71 +/- 0.86 vs. 5.00 +/- 2.95 ng/ml, p < 0.05) and IGF-1SDS (CF boys -1.43 +/- 1.50 vs. -0.32 +/- 0.88, p < 0.05; CF girls -0.66 +/- 1.66 vs. 0.64 +/- 0.57, p < 0.01) were lower in CF children compared to controls. Shwachman score was the strongest predictor of lean body mass (R = 0.63). Leptin levels explain 60% of the variability in FBM. CONCLUSION: Serum concentrations of IGF-1 and leptin are decreased in children with CF and are associated with clinical conditions and body composition.
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| 3. |
- Coya, R, et al.
(författare)
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Circulating non-22 kDa growth hormone isoforms after a repeated GHRH stimulus in normal subjects.
- 2005
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Ingår i: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. - : Elsevier BV. - 1096-6374. ; 15:2, s. 123-9
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the proportion of non-22 kDa GH isoforms in relation to total GH concentration after a repeated GHRH stimulus in healthy subjects. We studied 25 normal volunteers (12 males and 13 females, mean age 13.1 years, range 6-35), who received two GHRH bolus (1.5 mug/kg body weight, i.v.) administered separately by an interval of 120 minutes. The proportion of non-22 kDa GH was determined by the 22 kDa GH exclusion assay (GHEA), which is based on immunomagnetic extraction of monomeric and dimeric 22 kDa GH from serum, and quantitation of non-22 kDa GH isoforms using a polyclonal GH assay. Samples were collected at baseline and at 15-30 min intervals up to 240 min for total GH concentration. Non-22 kDa GH isoforms were measured in samples where peak GH after GHRH was observed. Total GH peaked after the first GHRH bolus in all subjects (median 37.2 ng/ml; range: 10.4-94.6). According to GH response to the second GHRH stimulus, the study group was divided in "non-responders" (n=7; 28%), with GH peak levels lower than 10 ng/ml (median GH: 8.7 ng/ml; range 7.3-9.6) and "responders" (n=18; 72%), who showed a GH response greater than 10 ng/ml (median 17 ng/ml; range 10.1-47.0). The median proportion of non-22 kDa GH on the peak of GH secretion after the first GHRH administration was similar in both groups ("responders" median: 8.6%, range 7-10.9%; "non-responders" median: 8.7%, range 6.7-10.3%), independently of the type of response after the second GHRH. In contrast, the median proportion of non-22 kDa GH was greater at time of GH peak after the second GHRH bolus in the "non-responders" (median 11.4%; range 9.1-14.3%) in comparison with the "responders" (median 9.1%; range 6.7-11.9%; p=0.003). A significant negative correlation between the total GH secreted and the percentage of non-22 kDa isoforms was seen in the "non-responders" (p=0.003). These differences in GH response to repeated GHRH stimulation and in the pattern of GH isoforms at GH peak among subjects might be due to distinct recovery patterns of somatrotrophic function and/or differences in metabolic clearance of GH isoforms.
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| 4. |
- Valuniene, M., et al.
(författare)
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Leptin levels at birth and in early postnatal life in small- and appropriate-for-gestational-age infants
- 2007
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Ingår i: Medicina (Kaunas). - 1648-9144. ; 43:10, s. 784-791
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate leptin concentration at birth and in early postnatal life in small- and appropriate-for-gestational-age infants and to assess its relationship with infants' anthropometry at birth and some characteristics of maternal pregnancy. MATERIALS AND METHODS. A total of 367 infants born after 32-42 weeks of gestation were enrolled in the study. Umbilical cord blood samples were collected from 80 small- and 287 appropriate-for-gestational-age newborns. Altogether, 166 venous blood samples were taken from these neonates on days 2-6 of life. RESULTS. Cord leptin levels were significantly lower in small- compared to appropriate-for-gestational-age infants. We observed a positive correlation between cord leptin and birth weight, all neonatal anthropometric parameters, placental weight, and some maternal nutritional factors. In multivariate analysis, cord leptin concentration explained up to 15% of the variation in sum of newborn's skinfold thickness but only 5% of the variation in birth weight. Postnatally, leptin concentration decreased markedly to the similar low levels in both infant groups and remained so during the first postnatal week. CONCLUSIONS. Significantly lower cord leptin concentration in small-for-gestational-age neonates reflects a lower fat mass content compared to appropriate-for-gestational-age infants. However, an abrupt decrease in leptin levels shortly after birth in both groups suggests that placenta could be an important source of leptin in fetal circulation. The impact of low leptin levels at birth in small-for-gestational-age infants on their postnatal appetite and weight gain remains to be elucidated in future studies.
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