Injection Of Growth Hormone Research Articles

Development of the Satisfaction Measure of the Injection of Growth Hormone (GH) Therapy (SMIGHTY TM) Questionnaire

Development of the Satisfaction Measure of the Injection of Growth Hormone (GH) Therapy (SMIGHTY TM) Questionnaire

Comparison of Intuitiveness, Ease of Use and Preference in Three Growth Hormone Injection Devices

Comparison of Intuitiveness, Ease of Use and Preference in Three Growth Hormone Injection Devices

Detecting growth hormone abuse in athletes

It is believed that athletes have been abusing growth hormone (GH) for its anabolic and lipolytic effects since the early 1980s, at least a decade before endocrinologists began to treat adults with GH deficiency. There is an on-going debate about whether GH is performance enhancing. Although many of the early studies were negative, more recent studies suggest that GH improves strength and sprint capacity, particularly when it is combined with anabolic steroids. Although use of GH is banned by the World Anti-Doping Agency (WADA), its detection remains challenging. Two approaches have been developed to detect GH abuse. The first is based on measurement of pituitary GH isoforms; after injection of recombinant human GH, which comprises solely the 22-kDa isoform, endogenous production is down-regulated leading to an increase in the 22-kDa isoform relative to other isoforms. The second is based on measurement of markers of GH action. Insulin-like growth factor-I (IGF-I) and N-terminal pro-peptide of type III collagen (P-III-NP) increase in response to GH administration in a dose-dependent manner. When combined with discriminant function analysis, use of these markers differentiates between individuals taking GH and placebo. Subsequent studies have shown that the test is applicable across different ethnicities and is unaffected by injury. WADA regulations state that when analytes are measured by immunoassay, two assays are needed. Final validation of the marker test is currently being undertaken with modern commercially available immunoassays to finalise the threshold values to be used to determine whether a doping offence has been committed.

New onset diabetes associated with bovine growth hormone and testosterone abuse in a young body builder

A 33-year-old male presented to the emergency department with complaints of polydipsia, polyuria, nausea, headaches, blurry vision and malaise. Lab work revealed a serum glucose level of 1166 mg/dl (64.8 mmol/L). The patient admitted to completing a cycle of androgenic anabolic steroids (AASs) for bodybuilding. His regimen consisted of supraphysiologic intramuscular injections of a bovine growth hormone, trenbolone acetate and testosterone. The patient received intravenous fluids and insulin to restore metabolic balance. Previously healthy with a non-contributory family history, he was diagnosed with new onset diabetes. It has been demonstrated that AAS use, specifically growth hormone, can affect glucose homeostasis through increasing cellular insulin resistance and reducing glucose uptake. Excess growth hormone has been shown to cause symptoms of acromegaly which predisposes up to 40% of patients to diabetes. As trenbolone acetate is not indicated for human use and athletes are known to use supraphysiologic doses of this underground, performance enhancing drug, the correlation of the timing of events and the use of this veterinary growth hormone likely exacerbated an underlying condition or caused this new onset diabetes. We report a case of a young bodybuilder with no significant past medical history who was diagnosed with new onset diabetes associated with supraphysiologic self-injections of the bovine growth hormone, trenbolone acetate, combined with testosterone. AAS have the potential to induce or exacerbate diabetic conditions due to decreased glucose tolerance and increased insulin resistance.

Growth hormone plus childhood low-dose estrogen in Turner's syndrome.

Short stature and ovarian failure are characteristic features of Turner's syndrome. Although recombinant human growth hormone is commonly used to treat the short stature associated with this syndrome, a randomized, placebo-controlled trial is needed to document whether such treatment increases adult height. Furthermore, it is not known whether childhood estrogen replacement combined with growth hormone therapy provides additional benefit. We examined the independent and combined effects of growth hormone and early, ultra-low-dose estrogen on adult height in girls with Turner's syndrome. In this double-blind, placebo-controlled trial, we randomly assigned 149 girls, 5.0 to 12.5 years of age, to four groups: double placebo (placebo injection plus childhood oral placebo, 39 patients), estrogen alone (placebo injection plus childhood oral low-dose estrogen, 40), growth hormone alone (growth hormone injection plus childhood oral placebo, 35), and growth hormone-estrogen (growth hormone injection plus childhood oral low-dose estrogen, 35). The dose of growth hormone was 0.1 mg per kilogram of body weight three times per week. The doses of ethinyl estradiol (or placebo) were adjusted for chronologic age and pubertal status. At the first visit after the age of 12.0 years, patients in all treatment groups received escalating doses of ethinyl estradiol. Growth hormone injections were terminated when adult height was reached. The mean standard-deviation scores for adult height, attained at an average age of 17.0±1.0 years, after an average study period of 7.2±2.5 years were -2.81±0.85, -3.39±0.74, -2.29±1.10, and -2.10±1.02 for the double-placebo, estrogen-alone, growth hormone-alone, and growth hormone-estrogen groups, respectively (P<0.001). The overall effect of growth hormone treatment (vs. placebo) on adult height was a 0.78±0.13 increase in the height standard-deviation score (5.0 cm) (P<0.001); adult height was greater in the growth hormone-estrogen group than in the growth hormone-alone group, by 0.32±0.17 standard-deviation score (2.1 cm) (P=0.059), suggesting a modest synergy between childhood low-dose ethinyl estradiol and growth hormone. Our study shows that growth hormone treatment increases adult height in patients with Turner's syndrome. In addition, the data suggest that combining childhood ultra-low-dose estrogen with growth hormone may improve growth and provide other potential benefits associated with early initiation of estrogen replacement. (Funded by the National Institute of Child Health and Human Development and Eli Lilly; ClinicalTrials.gov number, NCT00001221.).

Functional conservation and divergence of duplicated insulin-like growth factor 2 genes in grass carp ( Ctenopharyngodon idellus)

Insulin-like growth factor 2 (IGF2) is a potent mitogenic and survival factor involved in the regulation of growth, development and reproduction in animals. Only one IGF2 gene exists in mammals. Recently, two igf2 genes have been identified in zebrafish, which presumably resulted from gene duplication. However, sequence information of duplicated igf2s and their functional regulation in other teleost fish is still unknown. Here, we report the identification of two igf2 cDNAs in grass carp, Ctenopharyngodon idellus. Like their human ortholog, grass carp igf2a and igf2b mRNAs encoded two structurally distinct mature IGF peptides. Both of them were detected by RT-PCR throughout embryogenesis. Ubiquitous expression of igf2b mRNAs was observed in embryos, whereas igf2a mRNAs were expressed mainly in the notochord and brain with in situ hybridization. In adult fish, igf2b mRNAs were transcribed in multiple tissues, whereas igf2a mRNAs were detected mainly in the liver. Hepatic levels of igf2a and igf2b transcripts were both up-regulated by growth hormone injection. Furthermore, the levels of hepatic igf2a and igf2b mRNAs decreased significantly during starvation and were rebounded rapidly after re-feeding. Our results suggest that duplicated igf2 genes have evolved divergent yet played an overlapping biological role in regulating grass carp growth and development.

Intuitiveness, ease of use, and preference of a prefilled growth hormone injection pen: A noninterventional, randomized, open-label, crossover, comparative usability study of three delivery devices in growth hormone-treated pediatric patients

Background: Growth hormone (GH) is used to treat pediatric and adult GH deficiency (GHD) and growth failure in, among others, patients with Turner syndrome or children born small for gestational age. To improve treatment adherence, self-injection devices should be easy to learn, easy to use, and well accepted, especially in pediatric patients. Several GH pen devices are available, each with distinct features designed for specific patient needs. Objectives: This study compared injection time and intuitiveness of a prefilled test injection device (Norditropin FlexPro, Novo Nordisk A/S, Bagsværd, Denmark) with those of 2 commercially available durable injection devices (easypod, Merck Serono SA, Geneva, Switzerland; and Genotropin, Pfizer Inc, New York, New York) in GH-treated pediatric patients. Dose accuracy, application errors, intuitiveness, usability, device features, ease of learning, ease of use, and overall preference were also assessed. Methods: This noninterventional, randomized, openlabel, crossover study enrolled patients aged ≥10 to <18 years who were diagnosed with GHD or Turner syndrome or were born small for gestational age. Patients were allocated to an intuitiveness group (without instruction) or an instruction group and assigned to 1 of 3 sequences of device testing. For each device, time taken to deliver a mock injection of test medium (FlexPro) or GH (easypod and Genotropin) into an Eppendorf tube and the delivered dose were measured. Dose accuracy and application errors were assessed by a health care professional. Patients assessed the intuitiveness (intuitiveness group only), device features, ease of learning, ease of use, and overall preference of the devices using questionnaires. Results: Included in the study were 56 patients (mean [SD] age, 13.6 [2.1] years; 63% male; GHD, 44 patients; Turner syndrome, 3; born small for gestational age, 9): 30 in the intuitiveness group and 26 in the instruction group. In the intuitiveness group, the mean (SD) mock injection time was significantly shorter with FlexPro (47.0 [49.0] seconds) than with the easypod (219.2 [72.6] seconds; P < 0.001) or the Genotropin pen (95.1 [78.4] seconds; P < 0.01). In the instruction group, injection time was also shortest with FlexPro (30.7 [10.8] seconds vs 59.6 [13.1] with easypod and 40.7 [18.6] with the Genotropin pen; both, P < 0.001). Most patients (70%) ranked FlexPro as the most intuitive device (easypod, 0%; Genotropin, 30%). In both the intuitiveness and instruction groups, a significantly greater proportion of patients considered FlexPro easiest to learn compared with the easypod and Genotropin devices (both, P < 0.001), although more patients preferred the easypod or Genotropin devices than FlexPro with regard to appearance (intuitiveness group: FlexPro, 8 patients; easypod, 9; and Genotropin, 13; instruction group: FlexPro, 4; easypod, 10; and Genotropin, 12) and quality (intuitiveness group: FlexPro, 6 patients; easypod, 10; and Genotropin, 14; instruction group: FlexPro, 8; easypod, 12; and Genotropin, 6), and easy- pod's delivery feedback feature was preferred by more patients (intuitiveness group: FlexPro, 8 patients; easypod, 14; Genotropin, 8; instruction group: FlexPro, 8; easypod, 14; and Genotropin, 4). Dose accuracies (as assessed by weighing the delivered dose and calculating variation in the delivered dose by device) were 4.6% with FlexPro, 14.6% with easypod, and 20.6% with the Genotropin pen in the intuitiveness group, and 2.7% with FlexPro, 5.8% with easypod, and 24.4% with the Genotropin pen in the instruction group. Conclusion: In this study, Norditropin FlexPro was associated with shorter injection times, higher dose accuracy, and greater intuitiveness, and was rated as easier to learn compared with the easypod and Genotropin devices.

Short Stature, Shots and Shortcomings

Sir,A 5-year-old developmentally normal boy presented to theEmergency Room with respiratory distress for 2 days. Hehad short stature, hypertension and pallor. Investigationsrevealed highly elevated Serum creatinine, metabolicacidosis and hyperkalemia. A diagnosis of Chronic RenalFailure (CRF) was made and hemodialysis initiated. Thisboy had been under the care of an endocrinologist inanother hospital and had received five doses of recombinanthuman Growth Hormone (rhGH) injections at monthlyintervals for short stature. Surprisingly, his blood pressurehad never been checked earlier while a battery of costlyinvestigations for short stature had been done. A goodhistory and thorough clinical examination including bloodpressure measurement could have led to an early diagnosisand appropriate timely intervention in this child.Children with CRF are at high risk for growthretardation and decreased adult height. Therapy withrecombinant human growth hormone increases the growthrate and improves the height in prepubertal children withCRF. However, whether the final height is improved by thistreatment is unknown [1]. In the absence of evidence forindividual or societal benefit, pharmacologic rhGH therapyfor normal short stature does not appear cost beneficial. Ithas been estimated that the average cost of rhGH per inchof height attainment is US $52 000 [2]. Apart from the drugcost, other issues like costs for medical visits, IGF-Imonitoring, parental work time lost, school absence, andinjection supplies cannot be ignored. AlthoughrhGHtreatedindividualsmaybetallerthannontreatedindividuals,theyarestill relatively short compared with peers of normal height.Therefore, whether the small expected gain in height issubstantialenoughtomeritfrequentinjectionsforanumberofyears in children who do not have a disease is not clear.Additionally, there is no evidence that rhGH treatmentimproves health related quality of life or psychologicaladaptation[3]. A child with CRF can present as short staturein an endocrinology clinic. Hence, non-endocrinologicalcauses should also be considered while evaluating a childwith short stature. Bloodpressuremeasurementandestimationof blood urea and serum creatinine should be done routinely inall children with short stature. With growing sophistication oftechnology, the superspecialists have become increasinglydependent on technology / instruments to make a diagnosis.This has, unfortunately, led to clinical medicine taking a backseat. This has also made therapy more expensive, more tediousand more inhuman.References

Early life growth hormone treatment shortens longevity and decreases cellular stress resistance in long-lived mutant mice

Hypopituitary Ames dwarf mice were injected either with growth hormone (GH) or thyroxine for a 6-wk period to see whether this intervention would reverse their long life span or the resistance of their cells to lethal stresses. Ames dwarf mice survived 987 ± 24 d (median), longer than nonmutant control mice (664 ± 48), but GH-injected dwarf mice did not differ from controls (707 ± 9). Fibroblast cells from Ames dwarf mice were more resistant to cadmium than cells from nonmutant controls (LD(50) values of 9.98 ± 1.7 and 3.9 ± 0.8, respectively), but GH injections into Ames dwarf mice restored the normal level of cadmium resistance (LD(50)=5.8 ± 0.9). Similar restoration of normal resistance was observed for fibroblasts exposed to paraquat, methyl methanesulfonate, and rotenone (P<0.05 in each case for contrast of GH-treated vs. untreated dwarf mice; P<0.05 for dwarf vs. nonmutant control mice.) T4 injections into Ames dwarf mice, in contrast, did not restore normal life span. We conclude that the remarkable life-span extension of Ames dwarf mice, and the stress resistance of cells from these mice, depends on low levels of GH exposure in juvenile and very young adult mice.

Differential Effects of Insufflated, Subcutaneous, and Intravenous Growth Hormone on Bone Growth, Cognitive Function, and NMDA Receptor Subunit Expression

The objective of this study was to characterize the effect of inhalable growth hormone (GH) delivered by an insufflator to the lungs of hypophysectomized Sprague Dawley rats. In the first cohort, the safety and efficacy of the insufflated GH were evaluated. Three experimental groups (n = 7 per group) were treated with GH for 15 d: One group received sc injection of GH daily at 200 microg/kg (SC200). Two other groups received GH by insufflation daily: 200 microg/kg (INS 200) and 600 microg/kg (INS 600). In the second set of experiments, GH was administered in three routes [SC200, INS200, intravenous (IV200)] (n=10) for 5 d, and escape latency and N-methyl D-aspartate (NMDA) receptor expression were evaluated. In the first cohort, INS200 showed similar bioactivity as SC200 in growth promotion, tibial growth, as well as escape latency on the 12th day of treatment. Insufflated GH was well tolerated without significant inflammatory responses. In the second cohort, expression of the NMDA receptor 1 and 2B in hippocampus measured after 3 or 6 d of daily treatments were significantly higher in INS200 as compared to IV200, consistent with the improvement of the escape latency. In summary, the inhalable form of GH delivered by intratracheal insufflation was safe, and its bioactivity was comparable to sc injection both in promotion of growth and acquisition of learning ability. If applied properly to human, inhalable GH would be effective for growth promotion and possibly for several disorders caused by underexpression of NMDA receptors.

Pleiotropic modulation of thymic functions by growth hormone: from physiology to therapy

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, including proliferation of thymocytes and thymic epithelial cells (TEC). Accordingly, GH-transgenic mice, as well as animals and humans treated with exogenous GH, exhibit an enhanced cellularity in the organ. GH also stimulates the secretion of 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 organ, as ascertained by experimental studies with intrathymic injection of GH in normal mice and with GH-transgenic animals. Most likely, GH effects in the thymus are mediated by an IGF-1/IGF-1 receptor circuitry, which physiologically operates in nonstimulated conditions in both thymocytes and TECs. Since GH enhances thymus replenishment and increases intrathymic T-cell traffic, ultimately modulating thymocyte exit, it should be placed as a potential adjuvant therapeutic agent in the treatment of immunodeficiencies associated with thymic atrophy, and examples recently appeared in the literature are promising and strongly indicate that GH can be beneficial for individuals suffering severe immunodeficiency.

Timing of growth hormone treatment affects trabecular bone microarchitecture and mineralization in growth hormone deficient mice

Growth hormone (GH) is essential in the development of bone mass, and a growth hormone deficiency (GHD) in childhood is frequently treated with daily injections of GH. It is not clear what effect GHD and its treatment has on bone. It was hypothesized that GHD would result in impaired microarchitecture, and an early onset of treatment would result in a better recovery than late onset. Growth hormone deficient homozygous ( lit/lit) mice of both sexes were divided into two treatment groups receiving daily injections of GH, starting at an early (21 days of age) or a late time point (35 days of age, corresponding to the end of puberty). A group of heterozygous mice with normal levels of growth hormone served as controls. In vivo micro-computed tomography scans of the fourth lumbar vertebra were obtained at five time points between 21 and 60 days of age, and trabecular morphology and volumetric BMD were analyzed to determine the effects of GH on bone microarchitecture. Early GH treatment led to significant improvements in bone volume ratio ( p = 0.006), tissue mineral density ( p = 0.005), and structure model index ( p = 0.004) by the study endpoint (day 60), with no detected change in trabecular thickness. Trabecular number increased and trabecular separation decreased in GHD mice regardless of treatment compared to heterozygous mice. This suggests fundamental differences in the structure of trabecular bone in GHD and GH treated mice, reflected by an increased number of thinner trabeculae in these mice compared to heterozygous controls. There were no significant differences between the late treatment group and GHD mice except for connectivity density. Taken together, these results indicate that bone responds to GH treatment initiated before puberty but not to treatment commencing post-puberty, and that GH treatment does not rescue the structure of trabecular bone to that of heterozygous controls.

Anti-tumor effects of adenovirus containing human growth hormone sequences in a mouse model of human ovarian cancer

Women with ovarian cancer have a low survival rate and develop resistance to chemotherapy, so new approaches to treatment are needed. We unexpectedly found administration of a replication-deficient adenovirus containing human growth hormone sequences (AdXGH) was beneficial in a mouse model of human ovarian cancer. Intraperitoneal injections of AdXGH prolonged median survival from a mean of 31±1.2 to 40±1.4days in immunodeficient SCID mice given SKOV3.ip1 human ovarian cancer cells in the peritoneal cavity. Adenovirus containing human prolactin or del32-71growth hormone sequences had no effect. Repeated injection of growth hormone or implantation of tablets with sustained growth hormone release did not increase survival. Control mice had overlapping tumors throughout the peritoneal cavity and liver and frequent lung metastases 24days after tumor cell injection. Mice that received two injections of AdXGH had no lung metastases. Mice that received four injections had no lung or liver metastases and peritoneal fibrosis. They did not survive longer than mice that received two injections, but they had enlarged livers with hepatocellular changes, indicating that a limitation of increasing the dose is liver toxicity.

Growth hormone rescues hippocampal synaptic function after sleep deprivation

Sleep is required for, and sleep loss impairs, normal hippocampal synaptic N-methyl-D-aspartate (NMDA) glutamate receptor function and expression, hippocampal NMDA receptor-dependent synaptic plasticity, and hippocampal-dependent memory function. Although sleep is essential, the signals linking sleep to hippocampal function are not known. One potential signal is growth hormone. Growth hormone is released during sleep, and its release is suppressed during sleep deprivation. If growth hormone links sleep to hippocampal function, then restoration of growth hormone during sleep deprivation should prevent adverse consequences of sleep loss. To test this hypothesis, we examined rat hippocampus for spontaneous excitatory synaptic currents in CA1 pyramidal neurons, long-term potentiation in area CA1, and NMDA receptor subunit proteins in synaptic membranes. Three days of sleep deprivation caused a significant reduction in NMDA receptor-mediated synaptic currents compared with control treatments. When rats were injected with growth hormone once per day during sleep deprivation, the loss of NMDA receptor-mediated synaptic currents was prevented. Growth hormone injections also prevented the impairment of long-term potentiation that normally follows sleep deprivation. In addition, sleep deprivation led to a selective loss of NMDA receptor 2B (NR2B) from hippocampal synaptic membranes, but normal NR2B expression was restored by growth hormone injection. Our results identify growth hormone as a critical mediator linking sleep to normal synaptic function of the hippocampus.

Insulin-like growth factor-3 (IGF-3) in male and female gonads of the tilapia: Development and regulation of gene expression by growth hormone (GH) and 17α-ethinylestradiol (EE2)

Recently, in addition to IGF-1 and IGF-2 the existence of a third form of IGF, termed IGF-3, limited to fishes, to be present only in the gonads and encoded by a separate gene has been reported. However, no further data have been presented on IGF-3. The present study on tilapia ( Oreochromis niloticus) uses quantitative real-time PCR specific for tilapia IGF-1 and IGF-3. The organ distribution of IGF-3 mRNA in adult fish and the early ontogeny of IGF-3 in male and female gonads were studied. The potential sensitivity of IGF-3 to GH was revealed by intraperitoneal injections of bream GH using IGF-1 as control gene. The effects of 17α-ethinylestradiol (EE2) exerted after feeding of high EE2 doses and exposure to low environmentally relevant EE2 doses on IGF-3 expression in testis and ovary during early development were determined. Low IGF-3 mRNA expression levels were detected in most organs studied, with the highest extra-gonadal amount in the pituitary. During development, the IGF-3 gene was significantly upregulated in male but downregulated in female gonad. Injections of GH elevated IGF-1 mRNA in male and female liver and ovary. IGF-3 did not respond to GH treatment neither in ovary nor in testis. Both EE2 treatments resulted in significant downregulations of IGF-3 mRNA in testis while ovarian IGF-3 mRNA did not respond. Thus, IGF-3 may be involved in reproduction of fishes most likely in the male gonad only. Whether IGF-3 also has some physiological significance in ovary or other organs should be the topic of further studies.

A Comparison of the Growth Responses Following Intramuscular GHRH Plasmid Administration Versus Daily Growth Hormone Injections in Young Pigs

The efficacy of daily porcine growth hormone (GH) injections versus plasmid-driven porcine GH-releasing hormone (pGHRH) production to promote growth was assessed. Ten-day-old piglets were injected intramuscularly with 0.1, 1, or 3 mg pGHRH, or a control plasmid followed by electroporation. Plasmid constructs were driven by a synthetic muscle-specific promoter. A fifth group received daily injections of GH [0.15 mg/(kg.day)]. Control and pGHRH-treated pigs were pair-fed to GH-treated pigs. Body composition was assessed by dual-energy X-ray absorptiometry (DXA). Weight gains of GH- and pGHRH-treated pigs were greater than of controls (P < 0.001) due to greater lean mass accretion; fat accretion was similar across all treatments. Weight gain of pGHRH- and GH-treated pigs was similar for 6 weeks, but over the final 10 days, only pigs administered the highest plasmid dose maintained higher growth rates. Serum insulin-like growth factor-I (IGF-I) levels were two- to threefold higher in GH- and pGHRH-treated pigs than in controls after 4 weeks (P = 0.05), but subsequently decreased to control levels in the pGHRH-treated group. Organ weights were greater in GH- than pGHRH-treated and control piglets (P < 0.02). These results demonstrate that pGHRH transfer is effective for promoting growth and avoids the need for the frequent injections necessitated with peptide hormone use.

Growth hormone attenuates skeletal muscle changes in experimental chronic heart failure

Objective This study evaluated the effects of growth hormone (GH) on morphology and myogenic regulatory factors (MRF) gene expression in skeletal muscle of rats with ascending aortic stenosis (AAS) induced chronic heart failure. Design Male 90–100 g Wistar rats were subjected to thoracotomy. AAS was created by placing a stainless-steel clip on the ascending aorta. Twenty five weeks after surgery, rats were treated with daily subcutaneous injections of recombinant human GH (2 mg/kg/day; AAS-GH group) or saline (AAS group) for 14 days. Sham-operated animals served as controls. Left ventricular (LV) function was assessed before and after treatment. IGF-1 serum levels were measured by ELISA. After anesthesia, soleus muscle was frozen in liquid nitrogen. Histological sections were stained with HE and picrosirius red to calculate muscle fiber cross-sectional area and collagen fractional area, respectively. MRF myogenin and MyoD expression was analyzed by reverse transcription PCR. Results Body weight was similar between groups. AAS and AAS-GH groups presented dilated left atrium, left ventricular (LV) hypertrophy (LV mass index: Control 1.90 ± 0.15; AAS 3.11 ± 0.44; AAS-GH 2.94 ± 0.47 g/kg; p < 0.05 AAS and AAS-GH vs. Control), and reduced LV posterior wall shortening velocity. Soleus muscle fiber area was significantly lower in AAS than in Control and AAS-GH groups; there was no difference between AAS-GH and Control groups. Collagen fractional area was significantly higher in AAS than Control; AAS-GH did not differ from both Control and AAS groups. Serum IGF-1 levels decreased in AAS compared to Control. MyoD mRNA was significantly higher in AAS-GH than AAS; there was no difference between AAS-GH and Control groups. Myogenin mRNA levels were similar between groups. Conclusion In rats with aortic stenosis-induced heart failure, growth hormone administration increases MyoD gene expression above non-treated animal levels, preserves muscular trophism and attenuates interstitial fibrosis. These results suggest that growth hormone may have a potential role as an adjuvant therapy for chronic heart failure.

Growth hormone (GH) acts on the GH/IGF-system in adult tilapia liver and immune organs

Event Abstract Back to Event Growth hormone (GH) acts on the GH/IGF-system in adult tilapia liver and immune organs Natallia Shved1*, Giorgi Berishvilia2, Jean-François Baroiller3, Peter Mazel2, Manfred Reinecke1 and Elisabeth Eppler2 1 University of Zürich, Division of Neuroendocrinology, Institute of Anatomy, Switzerland 2 University of Zürich, Institute of Anatomy, Switzerland 3 Campus International de Baillarguet, CIRAD-EMVT UPR20, Aquaculture Unit, France In mammals, the GH/IGF-I and the immune system have been shown to interact. The stimulatory significance of GH for the immune system is indicated by the presence of the GH-receptor (GHR) and insulin-like growth factor (IGF)-I. However, little is known on the local regulation of the IGFs and the GHR in immune organs. There is evidence for interactions also in bony fish since the GHR, IGF-I and IGF-II are also found in different fish species including the tilapia. Immune regulation is important for aquaculture and wild-life fish and thus plays an increasing role in basic science and aquaculture research. To investigate the local regulation of IGF-I, IGF-II and GHR by GH adult tilapia (Oreochromis niloticus) were challenged with intraperitoneal GH injections. The expression levels of hepatic GHR and IGF-I and IGF-I serum levels were quantified. Hepatic GHR mRNA was downregulated and IGF-I mRNA elevated as well as IGF-I serum levels in the GH-injected fish. IGF-I gene expression in spleen and head kidney was raised, in the latter even stronger than in liver. In the spleen, in addition to IGF-I also IGF-II mRNA was strongly elevated. Thus, head kidney and spleen reacted differently to GH treatment indicating different roles of GH and the IGFs in growth, differentiation and sustainment in the immune system of the tilapia. Whether this also has implications for immune response demands for further studies using bacteria and other pathogens. Supported by Swiss National Foundation (Project nos. 111028, 118165) and Hartmann Müller-Foundation for Medical Research (Project no. 1115). Keywords: comparative endocrinology Conference: 25th Conference of the European Comparative Endocrinologists, Pécs, Hungary, 31 Aug - 4 Sep, 2010. Presentation Type: Conference Presentation Topic: Comparative endocrinology Citation: Shved N, Berishvilia G, Baroiller J, Mazel P, Reinecke M and Eppler E (2010). Growth hormone (GH) acts on the GH/IGF-system in adult tilapia liver and immune organs. Front. Endocrinol. Conference Abstract: 25th Conference of the European Comparative Endocrinologists. doi: 10.3389/conf.fendo.2010.01.00004 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 25 Aug 2010; Published Online: 29 Aug 2010. * Correspondence: Dr. Natallia Shved, University of Zürich, Division of Neuroendocrinology, Institute of Anatomy, Zürich, Switzerland, n.shved@anatom.uzh.ch Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Natallia Shved Giorgi Berishvilia Jean-François Baroiller Peter Mazel Manfred Reinecke Elisabeth Eppler Google Natallia Shved Giorgi Berishvilia Jean-François Baroiller Peter Mazel Manfred Reinecke Elisabeth Eppler Google Scholar Natallia Shved Giorgi Berishvilia Jean-François Baroiller Peter Mazel Manfred Reinecke Elisabeth Eppler PubMed Natallia Shved Giorgi Berishvilia Jean-François Baroiller Peter Mazel Manfred Reinecke Elisabeth Eppler Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

OR14,82 Biochemical markers of bone turnover in tibia fracture patients randomly assigned to growth hormone (GH) or placebo injections. Implications for detection of GH abuse

Abstract Context It has been argued that increased levels of bone remodelling markers are not suitable indicators of GH abuse, as bone injuries per se increase the expression levels of these markers. Objective To investigate the impact of a recovering tibia fracture on circulating bone markers in subjects receiving placebo or GH treatment. Design and setting A randomised, double-blind, placebo-controlled trial of up to 16 weeks GH treatment, followed by a 16-week washout. Participants and intervention Subjects (406 adult males and females) with a tibia fracture were randomly allocated within three days after surgery, to either placebo or GH treatment (15, 30 or 60 μg/kg daily) until fracture healing or 16 weeks after treatment initiation. Main outcome measures IGF-I, serum C-terminal telopeptide of type I collagen (CTX), osteocalcin (OST) and bone-specific alkaline phosphatase (BAP) were measured during and after treatment. Results Dose-dependent increases were observed in groups receiving GH, and mean levels in the highest GH dose group peaked at eight (IGF-I, CTX) or 12 weeks (OST) after treatment initiation. Statistically significant differences between GH treatment and placebo were seen for IGF-I, CTX and OST in all GH dose groups throughout the treatment period, and persisted until eight (CTX) or 12 (OST) weeks after cessation of treatment. Conclusion IGF-I, CTX and OST are suitable candidate markers of prolonged, illicit administration of GH. Furthermore, CTX and OST have potentials to serve as markers also after cessation of GH administration.

Additive Effects of Intra-articular Injection of Growth Hormone and Hyaluronic Acid in Rabbit Model of Collagenase-induced Osteoarthritis

In a rabbit model of collagenase-induced osteoarthritis, the additive effects of intra-articular recombinant human growth hormone (GH) administration to hyaluronic acid (HA) were evaluated. After intra-articular collagenase injection, mature New Zealand white rabbits (n=30) were divided into 3 groups. Group 1 (control rabbits) received once weekly intra-articular saline injections for 4 weeks. Group 2 rabbits received 6 mg HA injections, and group 3 rabbits were injected with 6 mg HA and 3 mg recombinant human GH. These injections were initiated 4 weeks after collagenase injections. Lameness was observed for 9 weeks after collagenase injections. Macroscopic and histopathological knee joint findings were also evaluated at the end of 9 weeks after collagenase injections. Although all animals had lameness after collagenase injections, the duration and severity of lameness were significantly shorter and less severe in group 3 than group 1 and 2 (P<0.01). Macroscopic scores showed that femoral condyles of group 3 rabbits received significantly less cartilage damage than those of groups 1 and 2 rabbits (P<0.01). Histopathological score was also the lowest in group 3 (P<0.01). These results suggest that co-injection of intra-articular HA and recombinant human GH is more effective than HA injections alone in an osteoarthritis model.