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| 2. |
- Barlind, Anna, 1978, et al.
(författare)
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The growth hormone secretagogue hexarelin increases cell proliferation in neurogenic regions of the mouse hippocampus.
- 2010
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Ingår i: Growth hormone & IGF research. - : Elsevier BV. - 1532-2238 .- 1096-6374. ; 20:1, s. 49-54
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Radiation therapy (RT) to the brain is often used in the treatment of children with different types of malignant diseases affecting the brain. However, RT in childhood may also have severe side effects including impaired brain maturation and intellectual development. For childhood cancer survivors these adverse effects of RT can cause lifelong disability and suffering. Therefore, there is an unmet need to limit late effects after RT. Precursor cells in the subgranular zone of the dentate gyrus (DG) in the hippocampus are particularly sensitive to irradiation (IR). This may be of significance as newly generated neurons in the DG are important for memory and learning. GH secretagogues (GHS) have previously been shown to promote neurogenesis and to have neuroprotective effects. In addition, several parts of the brain, including the hippocampus, have been shown to express the GHS receptor 1a (GHS-R1a). The aim of this study was to evaluate the potential effect of the GHS hexarelin on proliferation and survival of progenitor cells in the hippocampus after brain IR in a mouse model. DESIGN: In the present study, 10-day-old male mice received 6Gy cranial IR. Non-irradiated sham animals were used as controls. We treated one group of irradiated and one sham group with hexarelin (100mug/kg/day) for 28days and used immunohistochemical labeling of bromo-deoxy uridine (BrdU) and phospho-histone H3 of the granular cell layer of the DG to evaluate proliferation and cell survival after IR at postnatal day ten. RESULTS: Our results show that hexarelin significantly increased the number of BrdU-positive cells in the granule cell layer by approximately 50% compared to controls. CONCLUSION: The increased number of BrdU-positive cells in the granule cell layer suggests a partial restoration in the pool of proliferating cells by hexarelin after IR.
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| 8. |
- Burman, Pia, et al.
(författare)
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Large fat and skin necroses after deep subcutaneous injections of a slow-release somatostatin analogue in a woman with acromegaly.
- 2010
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Ingår i: Growth Hormone & Igf Research. - : Elsevier BV. - 1532-2238 .- 1096-6374. ; Dec, s. 438-440
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Somatostatin analogues are the most commonly used drugs for treatment of acromegaly. Known side effects include gastrointestinal reactions, cholelithiasis, effects on glucose metabolism, and mild reactions at injection sites. We report a patient who developed fat and skin necroses after injections of a depot somatostatin analogue. SUBJECT: A woman with active acromegaly was given deep subcutaneous injections of an extended release formulation of lanreotide at alternate sides of the buttocks on three occasions over a ten week period. The regimen was then discontinued due to gastrointestinal complaints. One month later indurated subcutaneous nodules appeared at both sites. After another two months, the patient presented 10×10cm lesions on the buttocks, with central erythematous zones and, at the site of two injections, a necrotic 5×3cm ulcer. There were no signs of infection or systemic diseases. MRI revealed bilateral fat necroses. A month later, an ulcer developed at the second site. The ulcers were managed conservatively until clear demarcations were obtained, where after surgical revisions were performed. Eight months after the last injection, the wounds could be closed. CONCLUSION: The fat and skin necroses represent a side-effect not previously described after deep subcutaneous injections. Possibly, the patient had an exceptional susceptibility to develop an inflammatory, foreign-body like reaction that hypothetically was aggravated by a sustained anti-angiogenic effect of the compound.
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| 9. |
- Bäck, Karolina, et al.
(författare)
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Changes in insulin and IGF-I receptor expression during differentiation of human preadipocytes
- 2009
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Ingår i: Growth Hormone & IGF Research. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 19:2, s. 101-111
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Tidskriftsartikel (refereegranskat)abstract
- Mature adipocytes originate from fibroblast-like precursor cells, preadipocytes, which differentiate to obtain the characteristics of adipocytes. Our aim was to investigate how differentiation of human preadipocytes affects the distribution of insulin receptors (IR) and IGF-I receptors (IGF-IR) and other cell characteristics. Preadipocytes were differentiated using indomethacine, dexamethasone, isobutyl-methylxantine (IBMX) and high concentration of insulin. Gene expression was quantified by real-time RT-PCT in preadipocytes (PA), differentiated preadipocytes (dPA) and mature adipocytes (mAD). The amount of expressed receptor protein was analyzed using receptor specific ELISAs and Western blot. We also studied DNA synthesis with radiolabeled thymidine incorporation and glucose accumulation with radiolabeled glucose. Differentiation of PA increased gene expression of IR but not IGF-IR, GLUT4, growth hormone receptor (GHR) and adiponectin appeared or increased. In PA and dPA only IR-A was expressed whereas also IR-B was detected in mAD. By Western blot and ELISA, IR and IGF-IR was phosphorylated by their own ligant at 1 nM and in dPA the acitivation of both receptors was stimulated by IGF-I, but not insulin, at 1 nM. Accumulation of glucose in PA was increased by insulin at 10 nM and by IGF-I at 1 nM and 10 nM. DNA synthesis was increased by insulin and IGF-I at 10 nM. In conclusion, both IR and IGF-IR are present in human preadipocytes and adipocytes. Differentiation is characterized by an increased IR/IGF-IR ratio.
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| 10. |
- Chisalita, Simona I., 1972-, et al.
(författare)
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Characterisation of receptors for IGF-I and insulin; evidence for hybrid insulin/IGF-I receptor in human coronary artery endothelial cells
- 2006
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Ingår i: Growth Hormone & Igf Research. - : Elsevier BV. - 1532-2238 .- 1096-6374. ; 16:4, s. 258-266
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Coronary artery disease is a prevalent cause of morbidity and mortality in diabetes. Little is known about insulin-like growth factor-I receptors (IGF-IR) and insulin receptors (IR) in human coronary endothelium. Our aim was to characterize IGF-IR and IR in human coronary artery endothelial cells (HCAEC). DESIGN: Cultured human coronary artery endothelial cells were used. Gene expression was measured by quantitative real-time RT-PCR analysis and receptor affinity by ligand binding. Receptor protein, phosphorylation of IGF-IR and IR beta-subunit as well as the presence of hybrid insulin receptor/Insulin-like growth factor-I receptor (Hybrid IR/IGF-IR) was analyzed by immunoprecipitation and Western blot. Postreceptor effects of insulin and IGF-I were assed by (3)H-thymidine incorporation. RESULTS: The gene expression of IGF-IR was several folds higher than that of IR. and insulin receptor isoform A (IR-A) was 20-fold more expressed than insulin receptor isoform B (IR-B) in HCAEC. The specific binding of (125)I-IGF-I was higher than that of (125)I-insulin. Insulin and the new long acting insulin analog, glargine, interacted with the IGF-IR with over thousand and 100-fold less potency than IGF-I itself, whereas IGF-II had 6 times lower potency than IGF-I. Phosphorylation of the IGF-IR beta-subunit was obtained by concentrations of 10(-10)-10(-8)M IGF-I, 10(-6)M of insulin, inconsistently by 10(-8)M insulin and not at all by 10(-10)-10(-9)M insulin. The IR beta-subunit was phosphorylated by insulin and IGF-I at concentrations of 10(-9)-10(-8)M. When immunoprecipitating with specific monoclonal anti-IR or anti-IGF-IR alpha-subunit antibodies we found bands situated in slightly different positions suggesting the presence of Hybrid IR/IGF-IR. IGF-I, IGF-II and insulin (10(-9)-10(-7)M) had no significant effect on (3)H-thymidine incorporation into DNA. CONCLUSIONS: Human coronary endothelial cells express more IGF-IR than IR, mainly IR-A, and also Hybrid IR/IGF-IR. Both IGF-I and insulin phosphorylate their receptors, but only IGF-I seems to phosphorylate Hybrid IR/IGF-IR. Our study provides experimental evidence for a possible role of IGF-IR, IR and Hybrid IR/IGF-IR in human coronary artery endothelial cells.
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| 11. |
- Coenen Schimke, J. M., et al.
(författare)
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A quantitative PCR measurement of messenger RNA expression of IGF-I, IGF-II and IGFBP-5 in human skeletal muscle
- 1999
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Ingår i: Growth Hormone & IGF Research. - : Elsevier. - 1096-6374 .- 1532-2238. ; 9:3, s. 179-186
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-like growth factor-I and -II (IGF-I and IGF-II) and their binding proteins are important components in growth promotion and tissue maintenance. We determined the presence of IGF-I, -II, and binding protein 5 (IGFBP-5) gene expression in human skeletal muscle and that mRNA abundance is not altered by nutrients and insulin. In the first protocol, (control) subjects were given water. In the second protocol, half of these subjects drank Polycose (carbohydrate) and the remaining subjects drank equal calories as a mixed meal. Quadriceps muscle biopsies were taken at 10 h. A semi-quantitative polymerase chain reaction was designed to measure gene expression. IGF-I, IGF-II and IGFBP-5 mRNA are present in adult human skeletal muscle, but no significant changes between meal groups were observed for IGF-I, IGF-II or IGFBP-5 mRNA levels, indicating that the expression of these genes are not altered acutely by nutrients and insulin.
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| 16. |
- Glad, Camilla A M, 1981, et al.
(författare)
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Rapid and high throughput genotyping of the growth hormone receptor exon 3 deleted/full-length polymorphism using a tagSNP.
- 2010
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Ingår i: Growth hormone & IGF research. - : Elsevier BV. - 1532-2238 .- 1096-6374. ; 20:3, s. 270-273
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The growth hormone (GH) receptor (GHR) exon 3 deleted/full-length (d3/fl) polymorphism has been suggested to affect GH sensitivity. The conventional genotyping method used for this polymorphism (multiplex PCR with fragment detection by gel electrophoresis) is laborious and requires large amount of DNA template. This has restricted analysis of this polymorphism to small cohorts. Our aim was to evaluate the accuracy of using a tagging single nucleotide polymorphism (tagSNP) as a marker for the d3/fl polymorphism. DESIGN: The d3/fl polymorphism was analyzed using TaqMan SNP genotyping of the tagSNP rs6873545 in 183 patients with adult GH deficiency (GHD). The results were compared to d3/fl genotypes determined by the conventional method. RESULTS: Genotyping success rate for the tagSNP was 100%. Frequency of the d3-allele was 24.0% (d3/d3 7.7%, d3/fl 32.2% and fl/fl 60.1%) and the results from the two different methods were identical. Moreover, three samples previously undetermined when genotyped using the conventional method were successfully analyzed using the tagSNP. CONCLUSION: The GHR d3/fl polymorphism can be studied by TaqMan SNP genotyping. Use of the tagSNP facilitates investigations of the effects of the d3/fl polymorphism in large cohorts.
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| 17. |
- Grant, P.A., et al.
(författare)
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Late pregnancy increases hepatic expression of insulin-like growth factor-I in well nourished guinea pigs
- 2005
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Ingår i: Growth Hormone & IGF Research. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 15:2, s. 165-171
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Tidskriftsartikel (refereegranskat)abstract
- Blood IGF-I concentrations are persistently elevated throughout pregnancy in humans and guinea pigs and may regulate substrate partitioning between mother and conceptus. In the guinea pig, liver and adipose tissue have recently been suggested to contribute to the increased levels of circulating IGF-I in mid-pregnancy, but whether this persists in late pregnancy in undernutrition is not known. Therefore the effect of pregnancy and undernutrition on circulating IGF-I and hepatic expression of IGF-I in late gestation in the guinea pig was examined. Female guinea pigs (Cavia porcellus) were fed ad libitum throughout pregnancy or 70% of ad libitum intake for 28 days prior to and throughout pregnancy (term is 69 d). Non-pregnant animals were maintained for 88 days on the same diets. Plasma IGF-I was measured by RIA after molecular sieving chromatography at low pH. Abundances of IGF-I and ß-actin mRNA in maternal liver were quantified by digoxigenin-ELISA after RT PCR. Late pregnancy increased both the concentration of IGF-I protein (p < 0.001) in plasma and the relative abundance of liver IGF-I mRNA (p < 0.001) in ad libitum fed, but not in feed restricted pregnant guinea pigs. The concentration of IGF-I protein in plasma correlated positively with the relative abundance of IGF-I mRNA in liver overall (p < 0.002), suggesting the liver as a major source of endocrine IGF-I in late pregnant guinea pigs. This study demonstrates that hepatic expression of IGF-I remains elevated during late pregnancy in the well fed guinea pig, which is in contrast to that observed in other non-human species. © 2005 Elsevier Ltd. All rights reserved.
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| 18. |
- Grönbladh, Alfhild, et al.
(författare)
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Administration of growth hormone and nandrolone decanoate alters mRNA expression of the GABAB receptor subunits as well as of the GH receptor, IGF-1, and IGF-2 in rat brain.
- 2014
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Ingår i: Growth Hormone & IGF Research. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 24:2-3, s. 60-66
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The illicit use of anabolic androgenic steroids (AAS), especially among young adults, is of major concern. Among AAS users it is common to combine the AAS nandrolone decanoate (ND), with intake of growth hormone (GH) and a connection between gonadal steroids and the GH system has been suggested. Both AAS and GH affect functions in the brain, for example those associated with the hypothalamus and pituitary, and several GH actions are mediated by growth factors such as insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2). The GABAergic system is implicated in actions induced by AAS and previous studies have provided evidence for a link between GH and GABAB receptors in the brain. Our aim was to examine the impact of AAS administration and a subsequent administration of GH, on the expression of GABAB receptors and important GH mediators in rat brain.DESIGN: The aim was to investigate the CNS effects of a high-dose ND, and to study if a low, but physiological relevant, dose of GH could reverse the ND-induced effects. In the present study, male rats were administered a high dose of ND every third day during three weeks, and subsequently the rats were given recombinant human GH (rhGH) during ten days. Quantitative PCR (qPCR) was used to analyze gene expression in hypothalamus, anterior pituitary, caudate putamen, nucleus accumbens, and amygdala.RESULTS: In the pituitary gland, the expression of GABAB receptor subunits was affected differently by the steroid treatment; the GABAB1 mRNA expression was decreased whereas a distinct elevation of the GABAB2 expression was found. Administration of ND also caused a decrease of GHR, IGF-1, and IGF-2 mRNA expression in the pituitary while the corresponding expression in the hypothalamus, caudate putamen, nucleus accumbens, and amygdala was unaffected. The rhGH administration did not alter the GABAB2 expression but increased the GABAB1 gene expression in the hypothalamus as compared to the AAS treated group.CONCLUSIONS: These results provide new insights on the impact of ND and GH on the brain and highlight the interaction of these hormones with systems influencing GABAB receptor expression. The physiological significance of the observed effects of these hormones is discussed.
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| 19. |
- Hansen-Pupp, Ingrid, et al.
(författare)
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Continuous longitudinal infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants: Evaluation of feasibility in a phase II study
- 2017
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Ingår i: Growth Hormone and IGF Research. - : Elsevier BV. - 1096-6374. ; 36, s. 44-51
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate the feasibility of continuous longitudinal intravenous infusion of recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 (rhIGF-1/rhIGFBP-3) for prevention of retinopathy of prematurity and other complications in extremely preterm infants (< 28 weeks' gestational age), based on initial sections of a phase II randomized controlled trial. Design The phase II trial was designed in four sections (A–D); we report pharmacokinetic and adverse events (AEs) data pooled for Sections B and C. Infants in these study sections received rhIGF-1/rhIGFBP-3 or standard neonatal care up to postmenstrual age (weeks + days) 28 + 6 (Section B) or 29 + 6 (Section C). Dosing was variable/individualized and intended to establish serum IGF-1 within physiological intrauterine levels. Results Nineteen infants were enrolled across Sections B/C: nine received rhIGF-1/rhIGFBP-3 and 10 standard neonatal care. Among the nine infants treated with study drug, mean (SD) dose was 95.1 (10.6) μg/kg/day and mean (SD) duration of infusion was 14.2 (6.1) days. Eight of nine (88.9%) treated infants had two or more dose changes during treatment. Mean serum IGF-1 levels during treatment were 23 μg/L among treated infants compared with 14 μg/L in control infants. Overall, 66.3% of IGF-1 measurements for treated infants were within target levels (20–60 μg/L) versus 17.3% for control infants. Overall incidence of adverse events (AEs) was similar for treated versus control infants; AEs were generally as expected in this population, and no AEs were considered related to study treatment. There was no observed increase in infection rates (considered a possible risk with continuous intravenous infusion) between treated and control infants. Rates of hypoglycemia (considered a possible risk with IGF-1 treatment) were also similar between groups. There was one fatal serious AE of cardiac tamponade in the treated group (not considered treatment related). Conclusion Infusion of rhIGF-1/rhIGFBP-3 increased serum concentrations of IGF-1 and attainment of target levels relative to standard neonatal care. rhIGF-1/rhIGFBP-3 infusion was well tolerated with no safety signals. Although further work is required to optimize the dose regimen for attainment of physiological intrauterine levels, we believe the results reported support the feasibility of rhIGF-1/rhIGFBP-3 continuous longitudinal infusion in extremely preterm infants. The trial is registered at ClinicalTrials.gov (NCT01096784). © 2017 The Authors
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| 20. |
- Hedman, Christina, 1964-, et al.
(författare)
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The IGF-system is not affected by a twofold change in protein intake in patients with type 1 diabetes
- 2005
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Ingår i: Growth Hormone & IGF Research. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 15:4, s. 304-310
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Tidskriftsartikel (refereegranskat)abstract
- Objective In type 1 diabetes the circulating IGF-system is altered with low IGF-I and changes in levels of IGF-binding proteins (IGFBPs) which may be of importance for the development of diabetes complications. Our aim was to study if IGF-I, as supported by experimental data in animals, can be affected by dietary protein intake.Design and methods Twelve patients with type 1 diabetes, age 37.5 ± 10.0 years (mean ± SD), diabetes duration 20.1 ± 9.3 years and HbA1c 6.3 ± 0.6% were allocated to isocaloric diets with either low normal protein content (LNP), (10 E%; 0.9 g protein/kg body weight) or high normal protein content (HNP) (20 E%; 1.8 g protein/kg body weight) in an open randomised cross-over study. Each diet was taken for 10 days with a wash-out period of 11 days in between. Circulating levels of total and free IGF-I and -II, IGFBP-1, -2 and -3 and GH-binding protein (GHBP) as well as ghrelin were measured with validated in-house immunoassays.Results At day 10, urinary urea excretion was 320 ± 75 mmol/24 h during LNP diet compared with 654 ± 159 mmol/24 h during HNP diet (p < 0.001). There were no changes in body weight or glycaemic control between the diets. Fasting levels of total IGF-I were 121 ± 33 μg/L after LNP and 117 ± 28 μg/L after HNP diet (ns) and the corresponding concentrations of IGFBP-1 were 142(141) and 132(157) μg/L [median (IQR)] (ns). There were no differences in plasma concentrations of total IGF-II, free IGF-I and -II, IGFBP-3, GHBP and ghrelin, whereas a small difference was found for IGFBP-2 (302 ± 97 vs. 263 ± 66 μg/L; LNP vs. HNP; p < 0.04).Conclusions A twofold change of the dietary protein intake does not influence the altered circulating IGF-system in type 1 diabetes. In order to affect the IGF-system other interventions must be used.
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| 21. |
- Hellgren, Gunnel, 1961, et al.
(författare)
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Safety aspects of longitudinal administration of IGF-I/IGFBP-3 complex in neonatal mice.
- 2011
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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. - 1532-2238. ; 21:4, s. 205-11
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Very preterm birth is associated with a high risk of morbidity. Infants born very preterm have low serum levels of insulin-like growth factor I (IGF-I), that further decrease after birth. IGF-I is essential for brain development and low serum levels have been associated with retinopathy of prematurity. The present study aimed to investigate the effects of prolonged administration of a low dose of rhIGF-I/rhIGFBP-3 on glucose levels and total body weight, as well as liver, spleen and brain weights, and gray and subcortical white matter in newborn mice. DESIGN: The study was performed as three different trials. In all experiments C57BL/6N mice were injected with a rhIGF-I/rhIGFBP-3 complex or saline. In the first experimental trial, blood glucose levels were assessed 30min, 1h, 1.5h, 3h, 6h, 24h and 48h after the rhIGF-I/rhIGFBP-3 or saline injection on postnatal day (PND) 6. In the second trial, mice were injected daily from PND 3 to 11 and sacrificed on PND 12 for analysis of IGF-I serum levels. In the third trial, body and organ weights and effects on gray and white matter were assessed on PND 18 after PND 3-11 treatments as above. Effects on gray and white matter were measured using immunoreactivity for microtubule-associated protein-2 (MAP-2), myelin basic protein (MBP), 2',3'-cyclic nucleotide 3' phosphodiesterase (CNPase), neurofilament and oligodendrocyte lineage transcription factor 2 (Olig2). RESULTS: Blood glucose levels were unchanged in the rhIGF-I/rhIGFBP-3-treated group compared to baseline. In the control group glucose levels increased 30min after the second saline injection; levels were not elevated at the subsequent time point. Three hours after the rhIGF-I/rhIGFBP-3 or saline, glucose levels were lower in rhIGF-I/rhIGFBP-3-treated animals than in saline treated (p=0.026). At PND 18, total body weight was higher in rhIGF-I/rhIGFBP-3-treated mice compared with controls (p<0.05), but there were no differences between groups in brain, liver or spleen weights. No differences in gray matter area were found between groups. Analyses of white matter markers showed an increased number of Olig2-positive cells in rhIGF-I/rhIGFBP-3-treated mice compared with controls (p<0.001). There were no differences between groups in terms of MBP, CNPase or neurofilament immunoreactivity. CONCLUSIONS: Prolonged administration of rhIGF-I/rhIGFBP-3 did not have a negative impact on blood glucose levels and was beneficial for total body growth.
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| 22. |
- Hellgren, Gunnel, 1961, et al.
(författare)
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The growth hormone receptor exon 3-deleted/full-length polymorphism and response to growth hormone therapy in prepubertal idiopathic short children
- 2015
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Ingår i: Growth Hormone & IGF Research. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 25:3, s. 127-135
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The primary aim of the study was to evaluate d3-GHR as a possible cause of increased GH sensitivity in children with delayed infancy-childhood transition (DICT). The secondary aim was to investigate the impact of the GHR exon 3 deleted/full-length (d3/f1) polymorphism on GH treatment response in prepubertal children classified as having idiopathic short stature (ISS). Design: Study subjects included 167 prepubescent longitudinally followed children classified as having ISS. Children were randomized to standard-dose GH treatment (33 mu g kg(-1) day(-1)), to double-dose treatment (67 mu g kg(-1) day(-1)), or to an untreated control group. Growth and metabolic outcome were evaluated at birth (n = 166), after one year of treatment (n = 59) and at adult height (n = 145). Genotyping of the GHR d3/f1 polymorphism was performed using TaqMan SNP genotyping of tagSNP rs6873545. Results: Birth and early growth data did not reach the predetermined level of statistical significance for difference between genotypes. Growth and IGF-1 response after one year of GH treatment did not differ between genotypes. IGFBP-3(SDS) was higher in untreated d3-GHR carriers than in untreated fl/fl individuals, whereas there was insufficient evidence for higher IGFBP-3(SDS) in treated d3-GHR carriers. Genotype did not explain the growth response to treatment, and no differences in height(SDS), height gain, or difference in height to midparental height(SDS) between genotype groups were found at adult height. Conclusion: The common GHR d3/fl polymorphism is probably not a cause of DICT in children with ISS, and our results do not suggest that the d3-GHR genotype is associated with increased sensitivity to GH in children with ISS.
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| 23. |
- Hellström, Ann, 1959, et al.
(författare)
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IGF-I in the clinics: Use in retinopathy of prematurity
- 2016
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Ingår i: Growth Hormone & Igf Research. - : Elsevier BV. - 1096-6374. ; 30-31, s. 75-80
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Tidskriftsartikel (refereegranskat)abstract
- Retinopathy of prematurity is a potentially blinding disease, which is associated with low neonatal IGF-I serum concentrations and poor growth. In severe cases impaired retinal vessel growth is followed by pathologic neovascularization, which may lead to retinal detachment. IGF-I may promote growth even in catabolic states. Treating preterm infants with recombinant human (rh) IGF-I to concentrations normally found during gestation has been suggested to have a preventative effect on ROP. A recent phase 2 study treating infants (gestational age between 23 weeks + 0 days and 27 weeks +6 days) with rhIGF-I/IGF binding protein-3 until 30 postmenstrual weeks showed no effect on ROP but a 53% reduction in severe bronchopulmonary dysplasia and 44% reduction in severe intraventricular hemorrhage. Oxygen is a major risk factor for ROP and during the phase 2 study oxygen saturation targets were increased to 90-95%, due to national guidelines, which might have affected ROP rate and severity making increased IGF-I a weaker preventative factor for ROP.
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| 24. |
- Hellström, Ann, 1959, et al.
(författare)
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The IGF system and longitudinal growth in preterm infants in relation to gestational age, birth weight and gender
- 2020
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Ingår i: Growth Hormone & Igf Research. - : Elsevier BV. - 1096-6374. ; 51, s. 46-57
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Growth factors in the blood of very preterm infants may reflect growth and contribute to the understanding of early development. We investigated postnatal levels of insulin-like growth factors (IGFs) in infants born very preterm and related them to early growth development. Design: Blood samples were analyzed weekly for IGF-I, IGF-II, IGF binding protein (BP)-1, IGFBP-3, and acid-label subunit (ALS). Methods: 73 children born very preterm (gestational age (GA) < 32 weeks) were divided according to their gender-specific birth weight standard deviation score (SDS) into either appropriate for GA (AGA) or small for GA (SGA). Fifty-two (71%) and forty-three (59%) infants completed follow-up with anthropometry at approximately 3 years and at 5 years of age respectively. Thirty-six subjects (49%) had blood sampling for IGF-I and IGFBP-3 measurements up to 3 years of age. Results: IGF-I, IGFBP-3, and ALS levels increased in all groups from week 31 to week 36, with generally lower levels in the SGAs, with a concomitant lower growth velocity. Postnatal ALS was strongly associated with IGF-I and IGFBP-3 in boys, girls and AGA infants. IGF-II was higher in earlier born preterms (GA < 27 weeks) at postmenstrual ages 27.5-29.9 weeks compared with SGAs and late GA (GA >= 27 weeks) preterms (p <.0001). IGF-II, in contrast to IGF-I, did not differ between SGAs and AGAs at weeks 31-36. Mean IGFBP-1 was highest in the SGAs compared to AGAs at mean week 28,5 and 31 (p=.001) and IGFBP-1 levels were elevated in relation to IGF-I in the SGAs at that period. At follow-up, the increase in IGF-I between week 31 and 33.5 was a significant positive determinant of height SDS at 3 and 5 years of age in forward multiple regression analysis, independent of target height. Conclusion: This is the first study to investigate postnatal ALS levels in preterm infants. In very preterm infants, IGF-II is less affected by size at birth during early postnatal weeks compared with IGF-I. Early elevated IGFBP-1 might protect the SGA infants from an intense metabolic rate. Our results indicate that anabolic and metabolic processes during weeks 31-36 predicts later height.
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| 25. |
- Henningson, Maria, et al.
(författare)
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Interactions between oral contraceptive status and GSTM1 and GSTT1 deletions on insulin-like growth factor-1 (IGF-1) plasma levels in young healthy women.
- 2010
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Ingår i: Growth Hormone & Igf Research. - : Elsevier BV. - 1532-2238 .- 1096-6374. ; Dec, s. 432-437
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Insulin-like growth factor-1 (IGF-1) is essential for the pubertal growth spurt and for normal mammary gland development. IGF-1 increases premenopausal breast cancer risk. Oral contraceptives (OCs) decrease IGF-1 in most women. The endogenous estrogens and their metabolites also influence IGF-1 levels. Glutathione S-transferases (GSTs) are involved in estrogen metabolism. We aimed to study IGF-1 levels and body size in relation to GSTM1 and GSTT1 deletions, and GSTP1*1B and current oral contraceptive (OC) status. DESIGN: Questionnaires on reproductive factors and OC use were completed and blood samples were obtained during menstrual cycle day 18-23 in healthy women (≤40years) from breast cancer high-risk families. IGF-1 was analyzed with radioimmunoassay. Genetic analyses were done with PCR based methods. Initially 258 women were included. After exclusion 229 women were finally included in the analyses of IGF-1 in relation to GSTM1 and GSTT1. RESULTS: Among the 142 non-OC users, GSTM1*0/*0 or GSTT1*0/*0 alone were associated with lower IGF-1 levels while homozygous GSTM1*0/*0/GSTT1*0/*0 carriers had higher IGF-1 levels (P(interaction)=0.024). In the 87 OC users, GSTM1*0/*0 or GSTT1*0/*0 alone were associated with higher IGF-1 levels while homozygous GSTM1*0/*0/GSTT1*0/*0 carriers had lower IGF-1 levels (P(interaction)=0.010). Among all 229 women, a three-way interaction model showed an interaction between the GSTM1*0/*0/GSTT1*0/*0 genotype and OC use on IGF-1 levels (P(interaction)=0.003). GSTP1*1B was not associated with IGF-1. The GSTM1*1/GSTT1*0/*0 genotype was associated with high body weight (P=0.003) and GSTM1*0/*0/GSTT1*0/*0 was associated with early growth (P=0.003). CONCLUSION: Both OC use and GSTT1 and GSTM1 genotypes may influence IGF-1 levels. Further studies are warranted to confirm our finding and elucidate the clinical importance.
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