Injection Of Growth Hormone Research Articles

P11 Comparison of intuitiveness, ease of use and preference in three growth hormone injection devices

P11 Comparison of intuitiveness, ease of use and preference in three growth hormone injection devices

The Effects of Growth Hormone (GH) Treatment on GH and Insulin/IGF-1 Signaling in Long-Lived Ames Dwarf Mice

The disruption of the growth hormone (GH) axis in mice promotes insulin sensitivity and is strongly correlated with extended longevity. Ames dwarf (Prop1(df), df/df) mice are GH, prolactin (PRL), and thyrotropin (TSH) deficient and live approximately 50% longer than their normal siblings. To investigate the effects of GH on insulin and GH signaling pathways, we subjected these dwarf mice to twice-daily GH injections (6 microg/g/d) starting at the age of 2 weeks and continuing for 6 weeks. This produced the expected activation of the GH signaling pathway and stimulated somatic growth of the Ames dwarf mice. However, concomitantly with increased growth and increased production of insulinlike growth factor-1, the GH treatment strongly inhibited the insulin signaling pathway by decreasing insulin sensitivity of the dwarf mice. This suggests that improving growth of these animals may negatively affect both their healthspan and longevity by causing insulin resistance.

Effect of Recombinant Human Growth Hormone on Random Pattern Flaps in Rats

Recombinant human growth hormone, a very potent anabolic hormone, plays a significant role in growth regulation, bone metabolism, and wound healing. This study evaluates its effect on random flap survival. Rats were randomly divided into 2 groups. A dorsal random flap, cephalically based, was used. One group received 5 mg/kg subcutaneous injection of recombinant human growth hormone 1 hour before surgery and a repeat dosage every 24 hours for 1 week. The others served as controls. At the end of 1 week, average weight and flap survival was evaluated. There was no difference in flap survival between the groups. Treated rats had gained significantly more weight. Recombinant human growth hormone had no beneficial effect on flap survival. The lack of a deleterious effect of the hormone on random flap survival and its significant effect on rat weight and well being supports its safe use during flap surgery.

The Effect of Intra-Hippocampal Injection of Growth Hormone on Spatial Learning and Memory in Animal Model of Alzheimer’s Disease

The aim of this study was to evaluate the effect of intra-hippocampal injection of Growth Hormone (GH) on impaired spatial cognition in rats with Alzheimer's Disease (AD). Growth hormone replacement therapy leading to improved cognition and well-being has mainly been carried in GH-deficient patients. Nevertheless, relatively only a few studies have investigated the function of GH in the brain. Aged Wistar male rats (350-400 g, 18-20 months old) were randomly divided into 6 groups (7 in each): Control (healthy aged); L; L + Veh; L + GH10; L + GH20 and L + GH40. Rats with AD-like cognitive deficiency was induced by injection of ibotenic acid into Nucleus Basalis of Meynert (NBM) bilaterally (5 microg 0.5 microL(-1), each side). A guide cannula was implanted in the right hippocampus under stereotaxic surgery for injection of human recombinant GH (10, 20 and 40 microg 2 microL(-1), during 5 min, twice daily, 9:00 am and 3:00 pm, for 7 days). All rats were trained in Morris water maze to evaluate the spatial learning and memory. Escape latency, traveled distance to find hidden platform and percent time spent in gaol qudrant did not differ between L and L + Veh groups, while latency and distance were reduced significantly. But percent time spent in gaol quadrant (without hidden platform) was increased significantly in NBM-lesioned rats treated with GH (L + GH groups) dose dependently to compare with vehicle treated group. These results suggest that intra-hippocampal injection of GH to aged rats with dementia type of AD (with NBM lesioned) could improve spatial cognition.

In vivo and in vitro effect of recombinant salmon growth hormone treatment on IGF-I and IGFBPs in yellowtail Seriola quinqueradiata

The role of growth hormone (GH) in regulating hepatic mRNA expression of insulin-like growth factor-I (IGF-I) and IGF binding proteins (IGFBPs) in yellowtail Seriola quinqueradiata was examined using in vivo and in vitro assays. Yellowtail hepatic IGF-I, IGFBP-1, IGFBP-2, IGFBP-3, and IGFBP-5 mRNAs were measured by real-time quantitative RT-PCR. Intraperitoneal injection of recombinant GH of chum salmon Oncorhynchus keta (rsGH) at a dose of 1 μg/g body weight resulted in a significant increases in hepatic IGF-I, IGFBP-3, and IGFBP-5 mRNA levels, whereas significant reductions in hepatic IGFBP-1 and IGFBP-2 mRNA levels were observed. For in vitro assays, liver slices were incubated with rsGH at different concentrations (doses: 0, 1, 10, 100, 500, and 1,000 ng/ml). Liver slices incubated with 100 ng/ml rsGH elicited a significant increase in IGF-I mRNA level. Similarly, a slight increase in IGFBP-3 and IGFBP-5 mRNA levels were also observed in liver explants incubated with rsGH. In contrast, a significant decline in IGFBP-1 mRNA levels was observed in liver slices incubated with 1,000 ng/ml rsGH. A slight decline in the level of IGFBP-2 mRNA was noted in liver explants with rsGH treatment. This study demonstrates the modulating effect of GH on the IGF system.

Clinical evaluation of recombinant human growth hormone injection in children with growth hormone deficiency

Recombinant human growth hormone (rhGH) has been widely used in the clinical treatment of growth hormone deficiency. To simplify the injection process and increase drug compliance, application of the GH injection has become a new treatment plan in recent years. The purpose of the current study was to evaluate the efficacy and safety of rhGH injection for the treatment of growth hormone deficiency (GHD) in children in China. In a nationwide, noncomparative, prospective, randomized, open trial, 31 children with confirmed complete GHD received subcutaneous injection of rhGH at 0.25 mg/kg·wk (0.107 IU/kg·d). The injection was given daily and the total weekly amount was separated into 6–7 injections. The patients were followed up at 3-month intervals and the treatment duration was 12 months. The height (HT), annual growth velocity (GV), mean height standard deviation score (HT SDS), blood serum insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3), and bone maturity before and after treatment were compared, and the safety of the treatment was analyzed. The mean HT, GV, and HT SDS were increased from 109.0±14 cm, 2.7±0.9 cm/yr, and −4.62 ±1.46 at baseline to 121.8±13.4 cm, 12.9±3.3 cm/yr, and −2.47±1.86 after 12 months of treatment, respectively (P<0.001). At the same time, blood IGF-I and IGFBP- 3 were increased significantly [41.27±64.43 μg/L vs 159.21±167.92 μg/L and 1540.00±1325.11 mg/L vs 3533.93±1413.82 mg/L, respectively (P<0.001)]. The bone age assessments performed 6 and 12 months after the treatment showed that no advanced bone maturation was noted. No serious adverse events occurred during the treatment, and the drug-related adverse events were mainly decreased thyroid function. We conclude that rhGH injection is a safe and effective drug for treatment of growth hormone deficiency in children.

Decrease in Adiponectin Levels Correlates to Growth Response in Growth Hormone-Treated Children

Background/Aims: Adiponectin is secreted by adipose tissue and circulates in human plasma at high levels. Decreased adiponectin levels are associated with insulin resistance and obesity. The aim of this study was to investigate whether changes in serum adiponectin levels are related to the growth response, insulin levels and insulin resistance during growth hormone (GH) treatment. Methods: The study included 94 short prepubertal children (19 girls and 75 boys). The mean age at the start of daily GH injections was 9.04 ± 2.38 years. Adiponectin levels in serum were measured using an ELISA. Results: At baseline, adiponectin correlated with the first-year growth response (r = 0.26, p = 0.012). Adiponectin decreased significantly after 1 week, 3 months and 1 year from 14.5 ± 5.71 to 13.1 ± 5.22 (p < 0.0001), 10.3 ± 4.82 (p < 0.0001) and 12.5 ± 5.34 μg/ml (p < 0.0001), respectively. There were significant correlations between the first-year growth response and the decrease in adiponectin levels after 3 months and 1 year (r = –0.38, p < 0.0001 and r = –0.47, p < 0.0001, respectively). No correlations between adiponectin, insulin and the homeostasis model assessment of insulin resistance were seen. Conclusions: GH treatment in prepubertal children decreases serum adiponectin levels, and the decrease is correlated to the growth response. No correlations between adiponectin and insulin levels or insulin resistance were found.

GROWTH HORMONE ATTENUATES MYOCARDIAL FIBROSIS IN RATS WITH CHRONIC PRESSURE OVERLOAD‐INDUCED LEFT VENTRICULAR HYPERTROPHY

1. The role of growth hormone (GH) in cardiac remodelling and function in chronic and persistent pressure overload-induced left ventricular hypertrophy has not been defined. The aim of the present study was to assess short-term GH treatment on left ventricular function and remodelling in rats with chronic pressure overload-induced hypertrophy. 2. Twenty-six weeks after induction of ascending aortic stenosis (AAS), rats were treated with daily subcutaneous injections of recombinant human GH (1 mg/kg per day; AAS-GH group) or saline (AAS-P group) for 14 days. Sham-operated animals served as controls. Left ventricular function was assessed by echocardiography before and after GH treatment. Myocardial fibrosis was evaluated by histological analysis. 3. Before GH treatment, AAS rats presented similar left ventricular function and structure. Treatment of rats with GH after the AAS procedure did not change bodyweight or heart weight, both of which were higher in the AAS groups than in the controls. After GH treatment, posterior wall shortening velocity (PWSV) was lower in the AAS-P group than in the control group. However, in the AAS-GH group, PWSV was between that in the control and AAS-P groups and did not differ significantly from either group. Fractional collagen (% of total area) was significantly higher in the AAS-P and AAS-GH groups compared with control (10.34 +/- 1.29, 4.44 +/- 1.37 and 1.88 +/- 0.88%, respectively; P < 0.05) and was higher still in the AAS-P group compared with the AAS-GH group. 4. The present study has shown that short-term administration of GH to rats with chronic pressure overload-induced left ventricular hypertrophy induces cardioprotection by attenuating myocardial fibrosis.

Growth Hormone Modulates Migration of Developing T Cells

In the context of the cross-talk between the neuroendocrine and immune systems, it is well known that growth hormone (GH) exerts physiological effects in central as well as peripheral compartments of the immune system. GH modulates a variety of thymic functions. For example, GH upregulates proliferation of thymocytes and thymic epithelial cells. Accordingly, GH-transgenic mice, as well as animals and humans treated with exogenous GH, exhibit an enhanced cellularity in the thymus organ. GH also stimulates the secretion of thymic hormones, cytokines, and chemokines by the thymic microenvironment as well as the production of extracellular matrix proteins. These effects lead to an increase in thymocyte migratory responses and intrathymic traffic of developing T cells, including the export of thymocytes from the thymus organ, as ascertained by experimental studies with intrathymic injection of GH in normal mice and with GH-transgenic animals. Because GH promotes a replenishment of the thymus and an increase of thymocyte export, it has been applied as a potential adjuvant therapeutic agent in the treatment of immunodeficiencies associated with thymic atrophy.

Economic evaluation of a weekly administration of a sustained-release injection of recombinant human growth hormone for the treatment of children with growth hormone deficiency

Purpose:From a societal perspective, we evaluated the cost-effectiveness of a novel sustained-release injection of recombinant human growth hormone (GH) administered on a weekly basis compared with that of the present daily GH injection for the treatment of children with GH deficiency. Methods:Health-related utility for GH therapy was measured based on the visual analogue scale. During July 2008, caregivers of 149 children receiving GH therapy form 2 study sites participated in a web-based questionnaire survey. The survey required the caregivers to rate their current subjective utility with daily GH injections or expected utility of weekly GH injections. Because there was no difference in the costs of the daily and weekly therapies, for the purposes of this study, only drug acquisition costs were considered. Results:Switching from daily to weekly injection of GH increased the utility from 0.584 to 0.784 and incurred an extra cost of 4,060,811 Korean won (KW) per year. The incremental cost-utility ratio (ICUR) for a base case was 20,305,055 KW per quality-adjusted life year (QALY) gained. Scenario analyses showed that the ICUR ranged from 15,751,198 to 25,489,929 KW per QALY. Conclusion:The ICUR for a base case and worst case scenario analyses ranged from 0.85 to 1.37-times per capita gross domestic product of Korea, which is considered to be within the generally accepted willingness-to-pay threshold. Thus, it is concluded that switching from daily to weekly injection of GH would be cost-effective.

Growth and Factors Affecting it in Thalassemia Major

In our thalassemic (T) cohort, 45% of them had height standard deviation score (HtSDS) less than −2 and 56% of them had growth velocity standard deviation score (GVSDS) less than −1. Their mid-arm circumference and triceps skin-fold thickness were decreased versus normal controls. Their circulating insulin-like growth factor-I (IGF-I) concentrations were significantly lower than normal children. Growth hormone (GH) response to provocation with clonidine and glucagon was defective in half of the short T children (peak GH < 7 ng/dL). Some of the short T children, with normal GH response to provocation, had defective spontaneous nocturnal GH secretion. IGF-I generation after one GH injection was reduced in T children than those with GH deficiency (GHD) and constitutional delay of growth and puberty (CDGP). GH therapy for a year significantly increased IGF-I concentrations, GV, and HtSDS in T children but to a lower level compared to those with GHD or CDGP, suggesting partial GH insensitivity. Pubertal induction with human chorionic gonadotropin in T adolescents was associated with increased IGF-I concentrations, GV, and HtSDS.

Adult‐onset deficiency in growth hormone and insulin‐like growth factor‐I alters oligodendrocyte turnover in the corpus callosum

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) provide trophic support during development and also appear to influence cell structure, function and replacement in the adult brain. Recent studies demonstrated effects of the GH/IGF-I axis on adult neurogenesis, but it is unclear whether the GH/IGF-I axis influences glial turnover in the normal adult brain. In the current study, we used a selective model of adult-onset GH and IGF-I deficiency to evaluate the role of GH and IGF-I in regulating glial proliferation and survival in the adult corpus callosum. GH/IGF-I-deficient dwarf rats of the Lewis strain were made GH/IGF-I replete via twice daily injections of GH starting at postnatal day 28 (P28), approximately the age at which GH pulse amplitude increases in developing rodents. GH/IGF-I deficiency was initiated in adulthood by removing animals from GH treatment. Quantitative analyses revealed that adult-onset GH/IGF-I deficiency decreased cell proliferation in the white matter and decreased the survival of newborn oligodendrocytes. These findings are consistent with the hypothesis that aging-related changes in the GH/IGF-I axis produce deficits in ongoing turnover of oligodendrocytes, which may contribute to aging-related cognitive changes and deficits in remyelination after injury.

OPPORTUNITY™

The mortality rate of maintenance hemodialysis (MHD) patients remains high. Measures of protein-energy wasting, including hypoalbuminemia, are strongly associated with their high mortality. Growth hormone (GH) may improve lean body mass (LBM) and serum albumin levels, and health-related quality of life (HRQoL), which are significantly and positively associated with survival in MHD patients. The OPPORTUNITY Trial will examine whether GH reduces mortality and morbidity and improves overall health in hypoalbuminemic MHD patients. The primary hypothesis is that daily recombinant human GH injections, compared with placebo, improve survival in hypoalbuminemic MHD patients. Secondary hypotheses are that GH improves morbidity and health, including number of hospitalized days, time to cardiovascular events, LBM, serum protein and inflammatory marker levels, exercise capacity, and HRQoL, and has a favorable safety profile. This is a prospective, double-blind, multicenter, randomized clinical trial involving 2500 MHD patients, up to 50% with diabetes mellitus, from 22 countries. Patients are randomized in a 1:1 ratio to receive daily injections of GH (20 microg/kg per day) or placebo for 104 weeks. Key inclusion criteria include clinically stable and well-dialyzed (Kt/V > or =1.2) adult MHD patients with serum albumin <4.0 g/dl. Exclusion criteria include active malignancy, active proliferative or severe nonproliferative diabetic retinopathy, uncontrolled hypertension, chronic use of high-dose glucocorticoids, or immunosuppressive agents and pregnancy. The OPPORTUNITY Trial is the first large-scale randomized clinical trial in adult MHD patients evaluating the response to GH of such clinical endpoints as mortality, morbidity, markers of body protein mass, inflammation, exercise capacity, and HRQoL.

Effect of testosterone and growth hormone injection before puberty on follicles size, rate of egg production and egg characteristics of the Mazandaran Native breeder hens

Egg shell quality and egg internal quality are of major importance to the egg industry worldwide. This experiment was conducted to evaluate the effect of testosterone and growth hormone (hGH) on egg production and characteristics. The aim of this trial is to test this hypothesis that one injection of these two hormones before puberty has any effects on egg production of Mazandaran native breeder hens. Two hundred native pullet used in a completely randomized design with 4 treatments, 5 replicates and 10 hens in each box. Hens were fed on common diet and hormones injected subcutaneously based on body weight (BW). The four treatments were: 1) injection of hGH (100 ig/kg BW), 2) injection of testosterone (500 ig/kg BW), 3) injection of hGH (100 ig/kg BW) + injection of testosterone (500 ig/kg BW) and 4) injection of 100 il distilled water (control). Injection was before 5% oviposition of flock (flock puberty). Egg production and characteristics were determined. Treatments affected ovary weight, small white, large white and small yellow follicles and some egg parameters. GH and testosterone can alter follicles size in ovary, and it is concluded that GH+testosterone injection is more effective on small and large follicles.

Seasonal and circadian time-dependent dual action of GH on somatic growth and ovarian development in the Asian catfish, Clarias batrachus (Linn.): Role of temperature

Effect of growth hormone (GH), injected either at the morning or evening, on the somatic and ovarian development of the Asian catfish, Clarias batrachus was studied during the late quiescence and early recrudescence phase of the reproductive cycle. GH treatment during the late quiescence phase (December–January; 11L: 13D, average water temperature 16.2 ± 1°C) failed to exert any impact on the somatic or ovarian development, except that it increased plasma testosterone marginally, and decreased hepatic level of triglycerides (TG); while during the early recrudescence phase (March–April; 12.4L: 11.20D; average water temperature—28.4 ± 2 °C), GH had significant circadian time-dependent effect on somatic and ovarian development. GH injection at morning stimulated ovarian growth and development, as was evident from the dose-dependent significant increase in ovarian weight, gonadosomatic index, plasma levels of testosterone and estradiol-17β following GH treatment. The ovarian morphology also revealed the advancement in follicular development in GH treated fish. GH also induced remarkable increase in ovarian levels of TG, free cholesterol (CF) and phospholipids (PL) with concomitant declines in their hepatic levels. However, evening hour GH injection provoked appreciable increase in body weight without having any significant impact on ovarian weight and GSI. Few oocytes in the ovary of evening hour GH treated fish exhibited advanced stages of development, but number of such advanced stage oocytes was significantly much less than the morning hour GH injected fish. Ovarian TG and PL remained unchanged, while their hepatic levels were increased. The temporal synergism between GH and other intrinsic factors regulating body growth and gonadal development may be suggested herewith to be considered prior to administration of GH in fishes. This study has immense practical use in aquaculture.

Growth Hormone Treatment for Growth Failure in Pediatric Patients with Crohn's Disease

To investigate the effect of human growth hormone (GH) injections on growth velocity in growth-impaired children with Crohn's disease (CD). Ten children and adolescents (mean age, 12.6 +/- 4.5 years; 6 males) with CD and poor height growth were treated with open-label recombinant GH, 0.043 mg/kg/day administered via subcutaneous injection, for 1 year. Patients were retrospectively matched with untreated patients (3 comparisons per case) by race, age, sex, and baseline height. Primary endpoint was height velocity; secondary endpoints were disease activity, body composition, and bone density determined by dual-energy x-ray absorptiometry scan. Mean height velocity increased by 5.33 +/- 3.40 (mean +/- standard deviation) cm/year in the GH-treated patients during the year of GH treatment, compared with 0.96 +/- 3.52 cm/year in the comparison group (P = .03). Height z-score increased by 0.76 +/- 0.38 in the treated group, compared with 0.16 +/- 0.40 in the comparison group (P < .01), and weight z-score increased by 0.81 +/- 0.89 in the treated group, compared with 0.00 +/- 0.57 in the comparison group (P < .01). Bone density revealed an increase of 0.31 +/- 0.33 in the lumbar spine z-score (P = .03 vs baseline). GH treatment increases height velocity and may enhance bone mineralization in children with CD. A randomized controlled trial in a large cohort of children is needed to evaluate the ultimate impact of GH treatment.

Canadian Clinical Experience and Patient Satisfaction With Easypod™—A New and Unique Growth Hormone Injection Device

Traditionally, growth hormone has been delivered by needle and syringe or manual injection devices that may be difficult and painful for patients. In January 2007, EMD Serono Canada, Inc., launched the Easypod™ in Canadian pediatric endocrine clinics. Easypod™ is the first electronic growth hormone injection device designed to improve patient's ease of use, reliability, and convenience.

Molecular characterization and gene expression analysis of insulin-like growth factors I and II in the redbanded seabream, Pagrus auriga: transcriptional regulation by growth hormone

Insulin-like growth factors (IGFs) I and II (IGF-I and IGF-II) play important roles in fish growth and development. The present study was aimed at isolating cDNAs encoding both IGF-I and IGF-II in the redbanded seabream ( Pagrus auriga), and at measuring relative gene expression levels in different organs and during larval development. A fragment of 1321 nucleotides coding for IGF-I was cloned from liver using 3′ and 5′ RACE techniques. It included an open reading frame of 558 nucleotides, encoding a 185-amino acid preproIGF-I. With respect to IGF-II, a fragment of 1544 nucleotides was cloned as well. The open reading frame spanned 648 nucleotides, rendering a 215-amino acid preproIGF-II. The deduced mature 67-amino acid IGF-I and 70-amino acid IGF-II exhibited high sequence identities with their corresponding fish counterparts, ranging between 88.6-100% and 79.1–98.5%, respectively. Real-time PCR showed the highest IGF-I transcripts in liver (∼ 200-fold higher than head-kidney). In contrast, the highest IGF-II mRNAs were detected in gills and heart (∼ 16-fold higher than head-kidney). In addition, both IGFs exhibited different gene expression patterns during larval development suggesting that their expression is developmentally regulated. IGF-I reached the highest expression levels at 18 days after hatching (11.6-fold higher than 1 day after hatching), whereas IGF-II expression did not change significantly. Both hepatic IGF-I and IGF-II mRNA levels increased sharply (3.1- and 19-fold higher than control, respectively) 3 h after injection of porcine growth hormone, but remained unchanged from 6 to 24 h after treatment. Our results are discussed in relation to those previously reported for other bony fish.

Measuring the benefits of growth hormone therapy in children: a role for preference-based approaches?

Recombinant human growth hormone has revolutionised the management of children with growth hormone deficiency, chronic renal insufficiency, Turner syndrome, Prader-Willi syndrome, small-for-gestational-age status, idiopathic short stature and other growth disorders...

Effect of testosterone and growth hormone injection before puberty on follicles size, rate of egg production and egg characteristics of the Mazandaran Native breeder hens

Egg shell quality and egg internal quality are of major importance to the egg industry worldwide. This experiment was conducted to evaluate the effect of testosterone and growth hormone (hGH) on egg production and characteristics. The aim of this trial is to test this hypothesis that one injection of these two hormones before puberty has any effects on egg production of Mazandaran native breeder hens. Two hundred native pullet used in a completely randomized design with 4 treatments, 5 replicates and 10 hens in each box. Hens were fed on common diet and hormones injected subcutaneously based on body weight (BW). The four treatments were: 1) injection of hGH (100 ig/kg BW), 2) injection of testosterone (500 ig/kg BW), 3) injection of hGH (100 ig/kg BW) + injection of testosterone (500 ig/kg BW) and 4) injection of 100 il distilled water (control). Injection was before 5% oviposition of flock (flock puberty). Egg production and characteristics were determined. Treatments affected ovary weight, small white, large white and small yellow follicles and some egg parameters. GH and testosterone can alter follicles size in ovary, and it is concluded that GH+testosterone injection is more effective on small and large follicles.