Current Research on Recombinant Human Growth Hormone and the Related Growth Factors, IGF-1 and GRF

1986 ◽  
Vol 75 (s325) ◽  
pp. 85-89 ◽  
Author(s):  
LINDA FRYKLUND
Keyword(s):  
Growth Hormone ◽  
Growth Factors ◽  
Human Growth Hormone ◽  
Recombinant Human Growth Hormone ◽  
Human Growth

Recombinant Human Growth Hormone Activates Neuroprotective Growth Factors in Hypoxic Brain Injury in Neonatal Mice

Endocrinology ◽  
2021 ◽  
Vol 162 (3) ◽  
Author(s):  
Susan Jung ◽  
Klara Terörde ◽  
Helmuth-Günther Dörr ◽  
Regina Trollmann
Keyword(s):  
Growth Hormone ◽  
Growth Factors ◽  
Brain Injury ◽  
Human Growth Hormone ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Neuroprotective Effects ◽  
Hypoxic Brain Injury ◽  
Hypoxic Brain

Abstract Perinatal hypoxia severely disrupts cerebral metabolic and maturational programs beyond apoptotic cell death. Antiapoptotic treatments such as erythropoietin are suggested to improve outcomes in hypoxic brain injury; however, the results are controversial. We analyzed the neuroprotective effects of recombinant human growth hormone (rhGH) on regenerative mechanisms in the hypoxic developing mouse brain in comparison to controls. Using an established model of neonatal acute hypoxia (8% O2, 6 hours), P7 mice were treated intraperitoneally with rhGH (4000 µg/kg) 0, 12, and 24 hours after hypoxic exposure. After a regeneration period of 48 hours, expression of hypoxia-inducible neurotrophic factors (erythropoietin [EPO], vascular endothelial growth factor A [VEGF-A], insulin-like growth factors 1 and 2 [IGF-1/-2], IGF binding proteins) and proinflammatory markers was analyzed. In vitro experiments were performed using primary mouse cortical neurons (E14, DIV6). rhGH increased neuronal gene expression of EPO, IGF-1, and VEGF (P < .05) in vitro and diminished apoptosis of hypoxic neurons in a dose-dependent manner. In the developing brain, rhGH treatment led to a notable reduction of apoptosis in the subventricular zone and hippocampus (P < .05), abolished hypoxia-induced downregulation of IGF-1/IGF-2 expression (P < .05), and led to a significant accumulation of endogenous EPO protein and anti-inflammatory effects through modulation of interleukin-1β and tumor necrosis factor α signaling as well as upregulation of cerebral phosphorylated extracellularly regulated kinase 1/2 levels (ERK1/2). Indicating stabilizing effects on the blood-brain barrier (BBB), rhGH significantly modified cerebrovascular occludin expression. Thus, we conclude that rhGH mediates neuroprotective effects by the activation of endogenous neurotrophic growth factors and BBB stabilization. In addition, the modification of ERK1/2 pathways is involved in neuroprotective actions of rhGH. The present study adds further evidence that pharmacologic activation of neurotrophic growth factors may be a promising target for neonatal neuroprotection.

Quantification of urinary insulin-like growth factors (IGFs) and IGF binding protein 3 in healthy volunteers before and after stimulation with recombinant human growth hormone

1995 ◽  
Vol 132 (4) ◽  
pp. 433-437 ◽  
Author(s):  
Burkhard Tönshoff ◽  
Werner F Blum ◽  
Mark Vickers ◽  
Sabine Kurilenko ◽  
Otto Mehls ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factors ◽  
Human Growth Hormone ◽  
Binding Protein ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Igf I ◽  
Before And After ◽  
Igfbp 3 ◽  
Insulin Like Growth Factors

Tönshoff B, Blum WF, Vickers M, Kurilenko S, Mehls 0, Ritz E. Quantification of urinary insulin-like growth factors (IGFs) and IGF binding protein 3 in healthy volunteers before and after stimulation with recombinant human growth hormone. Eur J Endocrinol 1995;132:433–7. ISSN 0804–4643 We examined excretion of urinary insulin-like growth factors I and II (IGF-I and IGF-II) and their major binding protein IGFBP-3 in comparison to their respective serum concentration in nine healthy female volunteers (median age 25 years, range 22–27) under baseline conditions and after stimulation with recombinant human growth hormone (rhGH), 4.5 IU twice daily subcutaneously for a period of 3 days. The IGFs were measured in unconcentrated urine by use of recently developed, highly sensitive radioimmunoassays. The IGFBP-3 was measured by a specific radioimmunoassay. The mean (±sd) urinary concentrations of IGF-I (0.08 ± 0.07 μg/l), IGF-II (1.02 ± 0.47 μg/l) and IGFBP-3 (19.1 ± 6.9 μg/l) were two to three orders of magnitude lower than in serum. The ratio of IGF-II over IGF-I concentration in urine (13:1) was five times higher than in serum (2.5:1), and the ratio of IGFBP-3 over the sum of IGF-I and IGF-II in urine (17:1) was four times higher than in serum (4:1). Urinary excretion was 63.3 ± 46.6 ng·m−2 · 24 h−1 for IGF-I, 1002 ± 598 ng·m−2 · 24 h−1 for IGFII and 18039 ± 4983 ng·m−2·24 h−1 for IGFBP-3. Using fast protein liquid exclusion chromatography, only immunoreactive IGFBP-3 components of less than 60 kD were detected in urine, with a major peak at 20kD. Urinary IGFBP-3 excretion correlated with serum IGFBP-3 (r = 0.61, p < 0.01) and the glomerular filtration rate (r = 0.56, p < 0.05) measured by steady-state inulin infusion clearances. Administration of rhGH stimulated significantly (p < 0.005) the serum IGF-I concentration by 50%, but not the urinary IGF-I excretion. In conclusion: the considerably higher ratio of IGF-II to IGF-I in urine compared to serum indicates that urinary IGF excretion does not represent only filtered IGFs, urinary IGF-I is a less sensitive indicator of GH activity than serum IGF-I, and as urinary IGFBP-3 excretion is in proportion to the glomerular filtration rate and serum IGFBP-3, it presumably reflects renal filtration of small immunoreactive IGFBP-3 fragments from the circulation. Burkhard Tönshoff, University Children's Hospital, Im Neuenheimer Feld 150, 69120 Heidelberg, Germany

The effect of treatment with recombinant human growth hormone (rhGH) on linear growth and adult height in children with idiopathic short stature (ISS): a systematic review and meta-analysis

2020 ◽  
Vol 33 (12) ◽  
pp. 1577-1588
Author(s):  
George Paltoglou ◽  
Ioannis Dimitropoulos ◽  
Georgia Kourlaba ◽  
Evangelia Charmandari
Keyword(s):  
Systematic Review ◽  
Growth Hormone ◽  
Short Stature ◽  
Human Growth Hormone ◽  
Adult Height ◽  
Linear Growth ◽  
Meta Analysis ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Idiopathic Short Stature

AbstractObjectivesIdiopathic short stature (ISS) is a recognized, albeit a controversial indication for treatment with recombinant human growth hormone (rhGH).The objective of the present study was to conduct a systematic review of the literature and meta-analyses of selected studies about the use of rhGH in children with ISS on linear growth and adult height (AH).MethodsA systematic literature search was conducted to identify relevant studies published till February 28, 2017 in the following databases: Medline (PubMed), Scopus and Cochrane Central Registry of Controlled Trials. After exclusion of duplicate studies, 3,609 studies were initially identified. Of those, 3,497 studies were excluded during the process of assessing the title and/or the abstract. The remaining 112 studies were evaluated further by assessing the full text; 21 of them fulfilled all the criteria in order to be included in the current meta-analysis.ResultsChildren who received rhGH had significantly higher height increment at the end of the first year, an effect that persisted in the second year of treatment and achieved significantly higher AH than the control group. The difference between the two groups was equal to 5.3 cm (95% CI: 3.4–7 cm) for male and 4.7 cm (95% CI: 3.1–6.3 cm) for female patients.ConclusionIn children with ISS, treatment with rhGH improves short-term linear growth and increases AH compared with control subjects. However, the final decision should be made on an individual basis, following detailed diagnostic evaluation and careful consideration of both risks and benefits of rhGH administration.

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