BACKGROUND Growth hormone(GH)plays a crucial role in wound healing and tissue repair in postoperative patients.In particular,colonic anastomosis healing following colorectal surgery is impaired by numerous chemotherap...BACKGROUND Growth hormone(GH)plays a crucial role in wound healing and tissue repair in postoperative patients.In particular,colonic anastomosis healing following colorectal surgery is impaired by numerous chemotherapy agents.AIM To investigate whether GH can improve the healing of a colonic anastomosis following the adverse effects of intraperitoneal administration of 5-fluorouracil(5-FU),bleomycin and cisplatin.METHODS Eighty Wistar rats underwent laparotomy and a 1 cm-resection of the transverse colon,followed by an end-to-end anastomosis under general anesthesia.The rats were blindly allocated into four equal groups and administered a different daily intraperitoneal therapeutic regimen for 6 days.The control group(A)received normal saline.Group B received chemotherapy with 5-FU(20 mg/kg),bleomycin(4 mg/kg)and cisplatin(0.7 mg/kg).Group C received GH(2 mg/kg),and group D received the aforementioned combination chemotherapy and GH,as described.The rats were sacrificed on the 7th postoperative day and the anastomoses were macroscopically and microscop-ically examined.Body weight,bursting pressure,hydroxyproline levels and inflammation markers were measured.RESULTS All rats survived until the day of sacrifice,with no infections or other complications.A decrease in the body weight of group D rats was observed,not statistically significant compared to group A(P=1),but significantly different to groups C(P=0.001)and B(P<0.01).Anastomotic dehiscence rate was not statistically different between the groups.Bursting pressure was not significantly different between groups A and D(P=1.0),whereas group B had a significantly lower bursting pressure compared to group D(P<0.001).All groups had significantly more adhesions than group A.Hydroxyproline,as a measurement of collagen deposition,was significantly higher in group D compared to group B(P<0.05),and higher,but not statistically significant,compared to group A.Significant changes in group D were recorded,compared to group A regarding inflammation(3.450 vs 2.900,P=0.016)and fibroblast activity(2.75 vs 3.25,P=0.021).Neoangiogenesis and collagen deposition were not signifi-cantly different between groups A and D.Collagen deposition was significantly increased in group D compared to group B(P<0.001).CONCLUSION Intraperitoneal administration of chemotherapy has an adverse effect on the healing process of colonic anastomosis.However,GH can inhibit the deleterious effect of administered chemotherapy agents and induce colonic healing in rats.展开更多
Previous studies have shown that growth hormone can regulate hypothalamic energy metabolism, stress, and hormone release. Therefore, growth hormone has great potential for treating hypothalamic injury. In this study, ...Previous studies have shown that growth hormone can regulate hypothalamic energy metabolism, stress, and hormone release. Therefore, growth hormone has great potential for treating hypothalamic injury. In this study, we established a specific hypothalamic axon injury model by inducing hypothalamic pituitary stalk electric lesions in male mice. We then treated mice by intraperitoneal administration of growth hormone. Our results showed that growth hormone increased the expression of insulin-like growth factor 1 and its receptors, and promoted the survival of hypothalamic neurons, axonal regeneration, and vascular reconstruction from the median eminence through the posterior pituitary. Altogether, this alleviated hypothalamic injury-caused central diabetes insipidus and anxiety. These results suggest that growth hormone can promote axonal reconstruction after hypothalamic injury by regulating the growth hormone-insulin-like growth factor 1 axis.展开更多
In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growt...In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.展开更多
Previous studies have shown that sericin extracted from silk cocoon significantly reduces blood glucose levels and protects the nervous system against diabetes mellitus. In this study, a rat type 2 diabetes mellitus m...Previous studies have shown that sericin extracted from silk cocoon significantly reduces blood glucose levels and protects the nervous system against diabetes mellitus. In this study, a rat type 2 diabetes mellitus model was established by intraperitoneal injection of 25 mg/kg streptozotocin for 3 successive days, following which the rats were treated with sericin for 35 days. After treatment, the blood glucose levels of the diabetic rats decreased significantly, the growth hormone level in serum and its expression in the hippocampus decreased significantly, while the insulin-like growth factor-1 level in serum and insulin-like growth factor-1 and growth hormone receptor expression in the hippocampus increased significantly. The experimental findings indicate that sericin improves disorders of the growth hormone/insulin-like growth factor 1 axis to alleviate hippocampal damage in diabetic rats.展开更多
AIM: Critical illnesses such as sepsis, trauma, and burns cause a growth hormone insensitivity, which leads to an increased negative nitrogen balance. Endotoxin is generously released into blood under these conditions...AIM: Critical illnesses such as sepsis, trauma, and burns cause a growth hormone insensitivity, which leads to an increased negative nitrogen balance. Endotoxin is generously released into blood under these conditions and stimulates the production of proinflammatory cytokines such as TNF-alpha, IL-6, and IL-1, which may play a very important role in inducing the growth hormone insensitivity. The objective of this current study was to investigate the role of endotoxin, TNF-alpha and IL-6 in inducing the growth hormone insensitivity at the receptor and post-receptor levels. METHODS: Spague-Dawley rats were injected with endotoxin, TNF-alpha, and IL-6, respectively and part of rats injected with endotoxin was treated with exogenous somatotropin simultaneously. All rats were killed at different time points. The expression of IGF-I, GHR, SOCS-3 and beta-actin mRNA in the liver was detected by RT-PCR and the GH levels were measured by radioimmunoassay, the levels of TNF-alpha and IL-6 were detected by ELISA. RESULTS: There was no significant difference in serous GH levels between experimental group and control rats after endotoxin injection, however, liver IGF-I mRNA expression had been obviously down-regulated in endotoxemic rats. Liver GHR mRNA expression also had a predominant down-regulation after endotoxin injection. The lowest regulation of liver IGF-I mRNA expression occurred at 12h after LPS injection, being decreased by 53% compared with control rats. For GHR mRNA expression, the lowest expression occurred at 8h and had a 81% decrease. Although SOCS-3 mRNA was weakly expressed in control rats, it was strongly up-regulated after LPS injection and had a 7.84 times increase compared with control rats. Exogenous GH could enhance IGF-I mRNA expression in control rats, but it did fail to prevent the decline in IGF-I mRNA expression in endotoxemic rats. Endotoxin stimulated the production of TNF-alpha and IL-6, and the elevated IL-6 levels was shown a positive correlation with increased SOCS-3 mRNA expression. The liver GHR mRNA expression was obviously down-regulated after TNF-alpha iv injection and had a 40% decrease at 8h, but the liver SOCS-3 mRNA expression was the 4.94 times up-regulation occurred at 40 min after IL-6 injection. CONCLUSION: The growth hormone insensitivity could be induced by LPS injection, which was associated with down-regulated GHR mRNA expression at receptor level and with up-regulated SOCS-3 mRNA expression at post-receptor level. The in vivo biological activities of LPS were mediated by TNF-alpha and IL-6 indirectly, and TNF-alpha and IL-6 may exert their effects on the receptor and post-receptor levels respectively.展开更多
Introduction: The impact of growth hormone therapy in children with short stature on cardiovascular prognosis seems to be unpredictable from big databases. The enhanced cardiovascular risk in this group of patients ma...Introduction: The impact of growth hormone therapy in children with short stature on cardiovascular prognosis seems to be unpredictable from big databases. The enhanced cardiovascular risk in this group of patients may be related to adverse autonomic imprinting by early life stress. Autonomic dysfunction and possible effects of growth hormone therapy on the autonomic nervous system can be measured easily by calculating heart rate variability (HRV) from Holter electrocardiogram monitoring. Methods: We performed HRV analysis prior to growth hormone therapy (N = 33), within the first year of growth hormone therapy between 4 and 10 years of age (N = 19), at least a further HRV measurement between 10 and 15 years (N = 30). Additional measurements were performed before and after cessation of growth hormone therapy (N = 14). Data were compared to untreated pediatric patients with short stature and to age matched healthy controls. Results: Untreated patients with short stature due to growth hormone deficiency or intrauterine growth restriction in early childhood have significantly increased heart rates most of all at night and concomitantly reduced global HRV indicated as Standard Deviation of Normal to Normal Intervals (SDNN). Growth hormone treated adolescents and the untreated patients with short stature show significantly elevated mean heart rates and concomitantly reduced vagus activities measured as reduced Route Mean Square Standard Deviation (RMSSD). After cessation of growth hormone treatment SDNN significantly increases and heart rate decreases to normal values in formerly treated patients with catch-up growth. Conclusion: There is a comparable autonomic dysfunction in treated and untreated children with short stature as an indicator for enhanced cardiovascular risk. After cessation of growth hormone therapy, we found a significant improvement of reduced HRV to normal values.展开更多
BACKGROUND The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass(DJB)surgery is not clear.AIM To study the morphological and functional changes in adipose tissue after DJB and explore the poten...BACKGROUND The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass(DJB)surgery is not clear.AIM To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model.METHODS DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model.All adipose tissue was weighed and observed under microscope.Use inguinal fat to represent subcutaneous adipose tissue(SAT)and mesangial fat to represent visceral adipose tissue.RNA-sequencing was utilized to evaluate gene expression alterations adipocytes.The hematoxylin and eosin staining,reverse transcription-quantitative polymerase chain reaction,western blot,and enzyme-linked immunosorbent assay were used to study the changes.Insulin resistance was evaluated by immunofluorescence.RESULTS After DJB,whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved.Fat cell volume in both visceral adipose tissue(VAT)and SAT increased.Compared to SAT,VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone(GH)pathway and downstream adiponectin secretion were involved in metabolic regulation.The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased.Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity.CONCLUSION GH improves insulin resistance in VAT in male diabetic rats after receiving DJB,possibly by increasing adiponectin secretion.展开更多
Background: The relationship between growth hormone (GH) and cytokines remains unclear. Several studies have suggested that GH increases tumor necrosis factor (TNF)-α production in both children and adults. However, ...Background: The relationship between growth hormone (GH) and cytokines remains unclear. Several studies have suggested that GH increases tumor necrosis factor (TNF)-α production in both children and adults. However, a number of studies have demonstrated a negative correlation between GH and TNF α. The aim of this study is to explore the relationship between endogenous GH secretion and certain pro and anti-inflammatory cytokines in short children undergoing GH stimulation testing for evaluation for GH deficiency. Methods: Plasma growth hormone, TNF α, CRP, IL-6, IL1-β, IL-4 and IL-10 levels are obtained at baseline and every 30 minutes for 150 minutes following two provocative agents (clonidine, and either arginine or glucagon). Results: Among the 23 children, 7 are found to be GH deficient. No significant differences in baseline TNF α levels are found between GH deficient and GH sufficient children. No correlation is identified between TNF α levels and GH levels during stimulation testing. Furthermore, no relationship is found between GH and pro-inflammatory cytokines or GH and anti-inflammatory cytokines. Conclusion: Our results do not demonstrate an acute relationship between endogenous GH secretion and the cytokines examined.展开更多
INTRODUCTIONCurrently the major treatment choices for shortbowel syndrome are parenteral nutrition and smallbowel transplantation.Both therapies involvegreat fiscal challenge and recurring complications.Recent years h...INTRODUCTIONCurrently the major treatment choices for shortbowel syndrome are parenteral nutrition and smallbowel transplantation.Both therapies involvegreat fiscal challenge and recurring complications.Recent years have witnessed the promisingexperimental results of pharmacologicalrehabilitation of remnant small bowel.展开更多
Oxidative stress has been involved in neurodegenerative diseases. The growth hormone (GH) counteracts the levels of reactive oxygen species. Previously, we showed that the prolonged exposure to ozone causes oxidative ...Oxidative stress has been involved in neurodegenerative diseases. The growth hormone (GH) counteracts the levels of reactive oxygen species. Previously, we showed that the prolonged exposure to ozone causes oxidative stress in the hippocampus and memory deficits. In this work, we analyzed the effects of the growth hormone on the memory deficit generated by ozone exposure, growth hormone effects on the Insulin-like growth factor I (IGF-I), and the serinethreonine protein kinase (Akt) activation in the dentate gyrus. Our results show that GH prevents memory deficits in early stages of the neurodegenerative process.展开更多
BACKGROUND The incidence of short stature in KBG syndrome is relatively high.Data on the therapeutic effects of growth hormone(GH)on children with KBG syndrome accompanied by short stature in the previous literature h...BACKGROUND The incidence of short stature in KBG syndrome is relatively high.Data on the therapeutic effects of growth hormone(GH)on children with KBG syndrome accompanied by short stature in the previous literature has not been summarized.CASE SUMMARY Here we studied a girl with KBG syndrome and collected the data of children with KBG syndrome accompanied by short stature from previous studies before and after GH therapy.The girl was referred to our department because of short stature.Physical examination revealed mild dysmorphic features.The peak GH responses to arginine and clonidine were 6.22 and 5.40 ng/mL,respectively.The level of insulin-like growth factor 1(IGF-1)was 42.0 ng/mL.Genetic analysis showed a c.2635 dupG(p.Glu879fs)mutation in the ANKRD11 gene.She received GH therapy.During the first year of GH therapy,her height increased by 0.92 standard deviation score(SDS).Her height increased from-1.95 SDS to-0.70 SDS after two years of GH therapy.There were ten children with KBG syndrome accompanied by short stature who received GH therapy in reported cases.Height SDS was improved in nine(9/10)of them.The mean height SDS in five children with KBG syndrome accompanied by short stature increased from-2.72±0.44 to-1.95±0.57 after the first year of GH therapy(P=0.001).There were no adverse reactions reported after GH treatment.CONCLUSION GH treatment is effective in our girl and most children with KBG syndrome accompanied by short stature during the first year of therapy.展开更多
BACKGROUND With the improvement of economy and living standards,the attention paid to short stature in children has been increasingly highlighted.Numerous causes can lead to short stature in children,among which growt...BACKGROUND With the improvement of economy and living standards,the attention paid to short stature in children has been increasingly highlighted.Numerous causes can lead to short stature in children,among which growth hormone deficiency(GHD)is a significant factor.AIM To investigate the long-term efficacy and safety of different doses of long-acting polyethylene glycol recombinant human growth hormone(PEG-rhGH)in the treatment of GHD in children.METHODS We selected 44 pediatric patients diagnosed with GHD who were treated at Wuhu First People's Hospital from 2014 to 2018.Total 23 patients were administered a high dose of long-acting PEG-rhGH at 0.2 mg/kg subcutaneously each week,forming the high-dose group.Meanwhile,21 patients were given a lower dose of long-acting PEG-rhGH at 0.14 mg/kg subcutaneously each week,establishing the low-dose Group.The total treatment period was 2 years,during which we monitored the patients’height,annual growth velocity(GV),height standard deviation score(HtSDS),chronological age(CA),bone age(BA),and serum levels of insulin-like growth factor-1(IGF-1)and insulin-like growth factor-binding protein-3(IGFBP-3)before treatment and at 6 mo,1 year,and 2 years after treatment initiation.We also monitored thyroid function,fasting plasma glucose,fasting insulin,and other side effects.Furthermore,we calculated the homeostatic model assessment for insulin resistance.RESULTS After 1 year of treatment,the GV,HtSDS,IGF-1,BA,and IGFBP-3 in both groups significantly improved compared to the pre-treatment levels(P<0.05).Moreover,when comparing GV,HtSDS,IGF-1,BA,and IGFBP-3 between the two groups,there were no statistically significant differences either before or after the treatment(P>0.05).During the treatment intervals of 0-1.0 years and 1.0-2.0 years,both patient groups experienced a slowdown in GV and a decline in HtSDS improvement(P<0.05).CONCLUSION The use of PEG-rhGH in treating GHD patients was confirmed to be effective,with similar outcomes observed in both the high-dose group and low-dose groups,and no significant differences in the main side effects.展开更多
Aim: To study effects of recombinant human growth hormone (rhGH) on growth hormone-insulin-like growth factor axis (GH-IGFs) of human gastric cancer cell in vivo in order to reveal part mechanism of growth effects of ...Aim: To study effects of recombinant human growth hormone (rhGH) on growth hormone-insulin-like growth factor axis (GH-IGFs) of human gastric cancer cell in vivo in order to reveal part mechanism of growth effects of rhGH on gastric cancer. Methods: Nude mice were randomly divided into control group, cisplatin (DDP) group, rhGH group and DDP + rhGH group after human gastric cancer xenograft model of node mice was successfully founded and drugs were used for 6 days. We investigated volume of tumor, inhibitory rate of tumor and cell cycle by slide gauge and flow cytometry. In addition, We also respectively investigated insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) of blood serum of nude mice, IGF-ImRNA, insulin-like growth factor-I receptor (IGF-IR) mRNA and IGFBP-3 mRNA of xenograft of nude mice by enzyme linked immunosorbent assay (ELISA) and semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) on the first day of completing use of drugs later. Results: Tumor grew obviously slowly and tumor inhibitory rate obviously rose in DDP group and DDP + rhGH group compared with control group and rhGH group (p p p < 0.05). Expressions of IGF-I mRNA and IGF-IR mRNA were not obviously different in all groups. But expression of IGFBP-3 mRNA obviously increased in rhGH group, DDP group and DDP + rhGH group compared with control group;meanwhile, expression of IGFBP-3 mRNA also obviously increased in DDP + rhGH group compared with control group, DDP group and rhGH group. Conclusion: Our results indicated rhGH in short-time use did not improve proliferation of human gastric cancer cells and its mechanism was possible that rhGH in short-time use raised simultaneously IGF-I and IGFBP-3 of blood serum and increased IGFBP-3 mRNA, but degraded ratio of IGF-I and IGFBP-3 of blood serum in human gastric cancer cells.展开更多
Objective:To study the protective effect of perioperative recombinant human growth hormone (r-hGH) application on intestinal mucosal barrier function in patients with intestinal obstruction and the influence on the im...Objective:To study the protective effect of perioperative recombinant human growth hormone (r-hGH) application on intestinal mucosal barrier function in patients with intestinal obstruction and the influence on the immune inflammatory response.Methods:60 patients with intestinal obstruction who underwent surgical treatment in our hospital between February 2013 and July 2016 were selected as the research subjects and divided into the control group (n=34) who received conventional surgical treatment and the observation group (n=26) who received surgery combined with perioperative r-hGH treatment. The serum levels of intestinal mucosal barrier indexes, immunoglobulin and inflammatory response indicators were compared between two groups of patients before and after treatment.Results: Before treatment, differences in serum levels of intestinal mucosal barrier indexes, immunoglobulin and inflammatory response indicators were not statistically significant between the two groups of patients. After treatment, serum intestinal mucosal barrier indexes Endotoxin, D-Lactate and DAO levels in observation group were lower than those in control group, immunoglobulin IgA, IgM and IgG levels were higher than those in control group, and inflammatory response indicators IL-1, IL-6, PCT and TNF-α levels were lower than those in control group patients. Conclusion:Perioperative r-hGH application in patients with intestinal obstruction can protect the intestinal mucosal barrier, also optimize the humoral immunity and suppress the systemic inflammatory response.展开更多
AIM:To determine the effects of RNAi-mediated inhibition of the growth hormone receptor(GHR)gene on tumors and colon cancer cells in vivo.METHODS:Construction of a eukaryotic vector for human GHR expression,the pcDNA ...AIM:To determine the effects of RNAi-mediated inhibition of the growth hormone receptor(GHR)gene on tumors and colon cancer cells in vivo.METHODS:Construction of a eukaryotic vector for human GHR expression,the pcDNA 6.2-GW/EmGFPsmall interfering RNAs(siRNAs)-GHR plasmid,was used to inhibit GHR expression.Thirty-six BALB/c nude mice were randomly divided into groups and treated with normal saline(NS),recombinant plasmid(G2),growth hormone(GH),5-fluorouracil(FU),G2+FU or G2+FU+GH.Each nude mouse was subcutaneously inoculated with 1×107human colon cancer SW480 cells;the nude mice were weighed before inoculation and on the 2nd,5th,8th,11th,14thand 17thday after inoculation.All nude mice were sacrificed after 17 d.Each subcutaneous tumor was removed and studied.Tumor volume was measured on the 5th,8th,11th,14thand 17thday after inoculation.The expression of GHR protein in the tumor tissue was detected by Western blotting analysis,and the differences in GHR mRNA expression in the tumor tissue were detected by real-time quantitative reverse transcription-polymerase chain reaction.RESULTS:Compared to the control group,the weights of the inoculated nude mice on the 17thday after inoculation were:G2:21.60±0.71 g,GH:21.64±0.45 g,FU:18.94±0.47 g,FU+G2:19.40±0.60 g,G2+FU+GH:21.04±0.78 g vs NS:20.68±0.66 g,P<0.05;the tumor volumes after the subcutaneous inoculation were:G2:9.71±3.82 mm3,FU:11.54±2.42mm3,FU+G2:11.42±1.11 mm3,G2+FU+GH:10.47±1.02 mm3vs NS:116.81±10.61 mm3,P<0.05.Compared to the GH group,the tumor volumes were significantly decreased in the experimental groups.The GHR protein expression(G2:0.39±0.02,FU:0.40±0.02,FU+G2:0.38±0.01,G2+FU+GH:0.39±0.01 vs NS:0.94±0.02,P<0.05)and the GHR mRNA expression(G2:14.12±0.10,FU:15.15±0.44,FU+G2:16.46±0.27,G2+FU+GH:15.37±0.57 vs NS:12.63±0.14,P<0.05)were significantly decreased and increased,respectively,in the experimental groups.CONCLUSION:Inhibition of GHR in human colon cancer SW480 cells resulted in anti-tumor effects in nude mice.展开更多
Growth Hormone （GH） is an important and powerful metabolic hormone that is secreted in a pulsatile pattern from cells in the anterior pituitary, influenced by several normal and pathophysiological conditions. Human ...Growth Hormone （GH） is an important and powerful metabolic hormone that is secreted in a pulsatile pattern from cells in the anterior pituitary, influenced by several normal and pathophysiological conditions. Human GH was first isolated in the 1950s and human derived cadaveric GH was initially used to treat patients with GH deficiency. However, synthetic recombinant GH has been widely available since the mid-1980s and the advent of this recombi- nant GH boosted the abuse of GH as a doping agent. Doping with GH is a well-known problem among elite athletes and among people training at gyms, but is forbidden for both medical and ethical reasons. It is mainly the anabolic and, to some extent, the lipolytic effects of GH that is valued by its users. Even though GH＇ s rumour as an effective ergogenic drug among athletes, the effectiveness of GH as a single doping agent has been questioned during the last few years. There is a lack of scientific evidence that GH in supraphysiological doses has additional effects on muscle exercise performance other than those obtained from optimised training and diet itself. However, there might be synergistic effects if GH is combined with, for example, anabolic steroids, and GH seems to have positive effect on collagen synthesis. Regardless of whether or not GH doping is effective, there is a need for a reliable test method to detect GH doping. Several issues have made the development of a method for detecting GH doping complicated but a method has been presented and used in the Olympics in Athens and Turin. A problem with the method used, is the short time span （24-36 hours） from the last GH administration during which the test effectively can reveal doping. Therefore, out-of-competition testing will be crucial. However, work with different approaches to develop an alternative, reliable test is ongoing.展开更多
The teleost Scatophagus argus is a species whose females grows faster than males.Growth hormone(gh)mRNA abundance in females pituitary is higher than that in males;however the mechanism underlining such differential i...The teleost Scatophagus argus is a species whose females grows faster than males.Growth hormone(gh)mRNA abundance in females pituitary is higher than that in males;however the mechanism underlining such differential is still unknown.Growth hormone(GH)is tightly associated with GH-releasing hormone(Ghrh)in vertebrates.In this study,Ghrh gene(ghrh)and its receptor gene,ghrhr,were isolated from S.argus.Tissue expression analysis showed that ghrh and ghrhr were mainly expressed in hypothalamus while ghrhr was expressed in pituitary and gh was predominantly expressed in pituitary.Twenty cultured S.argus individuals were used to compare ghrh,ghrhr and gh mRNA abundances,120 g and 181 g average weight for male(n=11)and female(n=9),respectively.Real-time PCR indicated that the ghrh and ghrhr mRNA abundances in male hypothalamus were significantly higher than those in female hypothalamus while that of gh mRNA abundance was significantly higher in female pituitary than in male pituitary.The ghrh and ghrhr mRNA abundances were significantly up-regulated in female hypothalamus 3 h after injection of 0.1 mg kg^-1 body weight Ghrh while pituitary ghrhr and gh mRNA abundances were not affected.In female hypothalamus,ghrh and ghrhr m RNA abundances were not affected at 6 h post-injection of 4 mg kg^-1 body weight 17α-methyltes-tosterone(17α-MT)or 17β-Estradiol(E2).In female pituitary,ghrhr m RNA abundance was down-regulated by 17α-MT while that of gh m RNA abundance was up-regulated by E2.Our findings indicated that E2,rather than Ghrh,plays an important role in up-regulating the expression of gh in female S.argus,which should aid to understand the sexual dimorphism of teleost growth.展开更多
Extrahepatic biliary obstruction promotes intestinal translocation of bacteria and endotoxin and this process is an important cause of morbidity and mortality in patients with jaundice. This study was undertaken to in...Extrahepatic biliary obstruction promotes intestinal translocation of bacteria and endotoxin and this process is an important cause of morbidity and mortality in patients with jaundice. This study was undertaken to investigate the effect and mechanism of recombinant human growth hormone (rhGH) and to alleviate intestinal translocation of bacteria and endotoxin in murine obstructive jaundice. METHODS:A group of 42 Wistar rats were divided into 3 groups:sham operation (SO), bile duct ligation (BDL), and BDL and rhGH treatment (rhGH). By the end of the experiment,on day 7, the animals were killed, and their liver function and serum endotoxin were measured, bacterial cultures of the liver, kidney and mesenchymal lymph were made. Terminal ileum mucosa was observed under an electron microscope. RESULTS:Liver function was improved more significantly in the rhGH group than in the BDL group. The value of endotoxin in the rhGH group was 0.38±0.03 EU/ml, significantly lower than that in the BDL group (0.65±0.04 EU/ml, P【0.01), and similar to that in the SO group (0.30±0.02 EU/ml, P】0.05). The rate of bacteria translocation in the liver, kidney and mesenteric lymph was much higher in the BDL group than in other two groups. The rate of bacteria translocation in mesenteric lymph was 64.29%,significantly higher than that in the SO group and the rhGH group (P【0.05). There was no significant difference in bacteria translocation rate between the SO group and the rhGH group (P】0.05). Under an electron microscope , ileum mucosa epithelial cells in the BDL group were necrotic, and organelle were markedly metamorphic. In the rhGH group, ultrastructural changes were less evident or similar to those in the SO group. CONCLUSION:rhGH has significant protective effects on intestinal mucosa barrier in obstructive jaundice, and reduces intestinal translocation of bacteria and endotoxin.展开更多
Growth hormone(GH)excess is associated with several systemic complications,one of which is the increased risk of neoplastic processes particularly of the gastrointestinal(GI)tract.Among the GI neoplasms,the most repor...Growth hormone(GH)excess is associated with several systemic complications,one of which is the increased risk of neoplastic processes particularly of the gastrointestinal(GI)tract.Among the GI neoplasms,the most reported association is with benign and malignant neoplasms of the colon.In the majority of published literature,an increased incidence of GI neoplasms,both colonic adenomas as well as colorectal carcinoma is reported.However,the studies on colon cancer-specific mortality rate are conflicting with recent studies reporting similar cancer-specific mortality rates in comparison to controls.Many studies have reported an association of colorectal neoplasms with GH levels.Pathogenic mechanisms put forward to explain this association of GH excess and GI neoplasms primarily involve the increased GH-insulin-like growth factor 1(IGF-1)signaling.Both GH and IGF-1 have proliferative,anti-apoptotic,and angiogenic effects on the systemic tissues leading to cellular proliferation.Other contributing factors to the increased risk of GI neoplasms include slow intestinal transit with a redundant large bowel,altered bile acids,deranged local immune response,shared genetic susceptibility factors and hyperinsulinemia.In view of the increased risk association,most guidelines for the care of acromegaly patients recommend an initial screening colonoscopy.Recommendations for further follow-up colonoscopy differ but broadly,the guidelines agree that it depends on the findings at first colonoscopy and state of remission of GH excess.Regarding the concern about the risk of colorectal cancers in patients receiving recombinant GH therapy,most cohort studies do not show an increased risk.展开更多
AIM: To investigate whether the simultaneous treatment with human growth hormone (hGH) abolishes the negative effects of everolimus on anastomotic healing.METHODS: Forty-eight male Sprague-Dawley-rats were randomized ...AIM: To investigate whether the simultaneous treatment with human growth hormone (hGH) abolishes the negative effects of everolimus on anastomotic healing.METHODS: Forty-eight male Sprague-Dawley-rats were randomized to three groups of 16 animals each (I: vehicle; II: everolimus 3 mg/kg po; III: everolimus 3 mg/kg po + hGH 2.5 mg/kg sc). Animals were pre-treated with hGH and/or everolimus daily for seven days. Then a standard anastomosis was created in the descending colon and treatment was continued for another seven days. The anastomosis was resected in toto and the bursting pressure was assessed as a mechanical parameter of intestinal healing. Moreover, biochemical (Hydroxyproline, PCNA, MPO, MMP-2 and MMP-9) and histological (cell density, angiogenesis, amount of granulation tissue) parameters of intestinal healing were assessed.RESULTS: Anastomotic bursting pressure was significantly reduced by everolimus and a simultaneous treatment with hGH resulted in considerably higher values (I: 134 ± 19 mmHg, II: 85 ± 25 mmHg, III: 114 ± 25 mmHg; P < 0.05, I vs II; P = 0.09, I vs III and II vs III) Hydroxyproline concentration was significantly increased by hGH compared to everolimus alone (I: 14.9 ± 2.5 μg/mg, II: 8.9 ± 3.6 μg/mg, III: 11.9 ± 2.8 μg/mg; P < 0.05, I vs II/III and II vs III). The number of MPO-positive cells was reduced significantly by hGH compared to everolimus alone (I: 10 ± 1 n/mm², II: 15 ± 3 n/mm², III: 9 ± 2 n/mm²; P < 0.05, I vs II and II vs III), while the number of PCNA-positive cells were increased by hGH (I: 28 ± 3 /mm², II: 12 ± 3 /mm², III: 26 ± 12 /mm²; P < 0.05, I vs II and II vs III). Corresponding to these biochemical findings, HE-histology revealed significantly increased amount of granulation tissue in hGH-treated animals.CONCLUSION: Inhibition of intestinal wound healing by everolimus is partially neutralized by simultaeous treatment with hGH. Both inflammation as well as collagen deposition is influenced by hGH.展开更多
文摘BACKGROUND Growth hormone(GH)plays a crucial role in wound healing and tissue repair in postoperative patients.In particular,colonic anastomosis healing following colorectal surgery is impaired by numerous chemotherapy agents.AIM To investigate whether GH can improve the healing of a colonic anastomosis following the adverse effects of intraperitoneal administration of 5-fluorouracil(5-FU),bleomycin and cisplatin.METHODS Eighty Wistar rats underwent laparotomy and a 1 cm-resection of the transverse colon,followed by an end-to-end anastomosis under general anesthesia.The rats were blindly allocated into four equal groups and administered a different daily intraperitoneal therapeutic regimen for 6 days.The control group(A)received normal saline.Group B received chemotherapy with 5-FU(20 mg/kg),bleomycin(4 mg/kg)and cisplatin(0.7 mg/kg).Group C received GH(2 mg/kg),and group D received the aforementioned combination chemotherapy and GH,as described.The rats were sacrificed on the 7th postoperative day and the anastomoses were macroscopically and microscop-ically examined.Body weight,bursting pressure,hydroxyproline levels and inflammation markers were measured.RESULTS All rats survived until the day of sacrifice,with no infections or other complications.A decrease in the body weight of group D rats was observed,not statistically significant compared to group A(P=1),but significantly different to groups C(P=0.001)and B(P<0.01).Anastomotic dehiscence rate was not statistically different between the groups.Bursting pressure was not significantly different between groups A and D(P=1.0),whereas group B had a significantly lower bursting pressure compared to group D(P<0.001).All groups had significantly more adhesions than group A.Hydroxyproline,as a measurement of collagen deposition,was significantly higher in group D compared to group B(P<0.05),and higher,but not statistically significant,compared to group A.Significant changes in group D were recorded,compared to group A regarding inflammation(3.450 vs 2.900,P=0.016)and fibroblast activity(2.75 vs 3.25,P=0.021).Neoangiogenesis and collagen deposition were not signifi-cantly different between groups A and D.Collagen deposition was significantly increased in group D compared to group B(P<0.001).CONCLUSION Intraperitoneal administration of chemotherapy has an adverse effect on the healing process of colonic anastomosis.However,GH can inhibit the deleterious effect of administered chemotherapy agents and induce colonic healing in rats.
基金supported by the Guangdong Basic and Applied Basic Research Foundation,Nos.2021A1515011371 (to JP),2021A1515110290 (to YO),2020A1515110564 (to XW)2023A 1 515010150 (to MZ)+2 种基金Science and Technology Planning Project of Guangzhou,No.202102020977 (to ZF)the National Natural Science Foundation of China,Nos.82201516 (to YO) and 81900709 (to ZF)President Foundation of Nanfang Hospital,Southern Medical University,Nos.2019C001 (to MZ),2019C016 (to XW), 2021C045 (to YO)。
文摘Previous studies have shown that growth hormone can regulate hypothalamic energy metabolism, stress, and hormone release. Therefore, growth hormone has great potential for treating hypothalamic injury. In this study, we established a specific hypothalamic axon injury model by inducing hypothalamic pituitary stalk electric lesions in male mice. We then treated mice by intraperitoneal administration of growth hormone. Our results showed that growth hormone increased the expression of insulin-like growth factor 1 and its receptors, and promoted the survival of hypothalamic neurons, axonal regeneration, and vascular reconstruction from the median eminence through the posterior pituitary. Altogether, this alleviated hypothalamic injury-caused central diabetes insipidus and anxiety. These results suggest that growth hormone can promote axonal reconstruction after hypothalamic injury by regulating the growth hormone-insulin-like growth factor 1 axis.
基金This work was supported by the Special Project of Performance Incentive and Guidance for Scientific Research Institutions of Chongqing,China (jxyn2022-5)。
文摘In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.
基金sponsored by the Natural Science Foundation of Hebei Province,H2012406018,H2013406096a grant from Hebei Province Department of Education,No.2006301
文摘Previous studies have shown that sericin extracted from silk cocoon significantly reduces blood glucose levels and protects the nervous system against diabetes mellitus. In this study, a rat type 2 diabetes mellitus model was established by intraperitoneal injection of 25 mg/kg streptozotocin for 3 successive days, following which the rats were treated with sericin for 35 days. After treatment, the blood glucose levels of the diabetic rats decreased significantly, the growth hormone level in serum and its expression in the hippocampus decreased significantly, while the insulin-like growth factor-1 level in serum and insulin-like growth factor-1 and growth hormone receptor expression in the hippocampus increased significantly. The experimental findings indicate that sericin improves disorders of the growth hormone/insulin-like growth factor 1 axis to alleviate hippocampal damage in diabetic rats.
基金the key,project of the tenth-five foundation of PLA,No.01Z011
文摘AIM: Critical illnesses such as sepsis, trauma, and burns cause a growth hormone insensitivity, which leads to an increased negative nitrogen balance. Endotoxin is generously released into blood under these conditions and stimulates the production of proinflammatory cytokines such as TNF-alpha, IL-6, and IL-1, which may play a very important role in inducing the growth hormone insensitivity. The objective of this current study was to investigate the role of endotoxin, TNF-alpha and IL-6 in inducing the growth hormone insensitivity at the receptor and post-receptor levels. METHODS: Spague-Dawley rats were injected with endotoxin, TNF-alpha, and IL-6, respectively and part of rats injected with endotoxin was treated with exogenous somatotropin simultaneously. All rats were killed at different time points. The expression of IGF-I, GHR, SOCS-3 and beta-actin mRNA in the liver was detected by RT-PCR and the GH levels were measured by radioimmunoassay, the levels of TNF-alpha and IL-6 were detected by ELISA. RESULTS: There was no significant difference in serous GH levels between experimental group and control rats after endotoxin injection, however, liver IGF-I mRNA expression had been obviously down-regulated in endotoxemic rats. Liver GHR mRNA expression also had a predominant down-regulation after endotoxin injection. The lowest regulation of liver IGF-I mRNA expression occurred at 12h after LPS injection, being decreased by 53% compared with control rats. For GHR mRNA expression, the lowest expression occurred at 8h and had a 81% decrease. Although SOCS-3 mRNA was weakly expressed in control rats, it was strongly up-regulated after LPS injection and had a 7.84 times increase compared with control rats. Exogenous GH could enhance IGF-I mRNA expression in control rats, but it did fail to prevent the decline in IGF-I mRNA expression in endotoxemic rats. Endotoxin stimulated the production of TNF-alpha and IL-6, and the elevated IL-6 levels was shown a positive correlation with increased SOCS-3 mRNA expression. The liver GHR mRNA expression was obviously down-regulated after TNF-alpha iv injection and had a 40% decrease at 8h, but the liver SOCS-3 mRNA expression was the 4.94 times up-regulation occurred at 40 min after IL-6 injection. CONCLUSION: The growth hormone insensitivity could be induced by LPS injection, which was associated with down-regulated GHR mRNA expression at receptor level and with up-regulated SOCS-3 mRNA expression at post-receptor level. The in vivo biological activities of LPS were mediated by TNF-alpha and IL-6 indirectly, and TNF-alpha and IL-6 may exert their effects on the receptor and post-receptor levels respectively.
文摘Introduction: The impact of growth hormone therapy in children with short stature on cardiovascular prognosis seems to be unpredictable from big databases. The enhanced cardiovascular risk in this group of patients may be related to adverse autonomic imprinting by early life stress. Autonomic dysfunction and possible effects of growth hormone therapy on the autonomic nervous system can be measured easily by calculating heart rate variability (HRV) from Holter electrocardiogram monitoring. Methods: We performed HRV analysis prior to growth hormone therapy (N = 33), within the first year of growth hormone therapy between 4 and 10 years of age (N = 19), at least a further HRV measurement between 10 and 15 years (N = 30). Additional measurements were performed before and after cessation of growth hormone therapy (N = 14). Data were compared to untreated pediatric patients with short stature and to age matched healthy controls. Results: Untreated patients with short stature due to growth hormone deficiency or intrauterine growth restriction in early childhood have significantly increased heart rates most of all at night and concomitantly reduced global HRV indicated as Standard Deviation of Normal to Normal Intervals (SDNN). Growth hormone treated adolescents and the untreated patients with short stature show significantly elevated mean heart rates and concomitantly reduced vagus activities measured as reduced Route Mean Square Standard Deviation (RMSSD). After cessation of growth hormone treatment SDNN significantly increases and heart rate decreases to normal values in formerly treated patients with catch-up growth. Conclusion: There is a comparable autonomic dysfunction in treated and untreated children with short stature as an indicator for enhanced cardiovascular risk. After cessation of growth hormone therapy, we found a significant improvement of reduced HRV to normal values.
基金Supported by National Natural Science Foundation of China(General Program),No.82070852 and No.82270901.
文摘BACKGROUND The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass(DJB)surgery is not clear.AIM To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model.METHODS DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model.All adipose tissue was weighed and observed under microscope.Use inguinal fat to represent subcutaneous adipose tissue(SAT)and mesangial fat to represent visceral adipose tissue.RNA-sequencing was utilized to evaluate gene expression alterations adipocytes.The hematoxylin and eosin staining,reverse transcription-quantitative polymerase chain reaction,western blot,and enzyme-linked immunosorbent assay were used to study the changes.Insulin resistance was evaluated by immunofluorescence.RESULTS After DJB,whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved.Fat cell volume in both visceral adipose tissue(VAT)and SAT increased.Compared to SAT,VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone(GH)pathway and downstream adiponectin secretion were involved in metabolic regulation.The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased.Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity.CONCLUSION GH improves insulin resistance in VAT in male diabetic rats after receiving DJB,possibly by increasing adiponectin secretion.
文摘Background: The relationship between growth hormone (GH) and cytokines remains unclear. Several studies have suggested that GH increases tumor necrosis factor (TNF)-α production in both children and adults. However, a number of studies have demonstrated a negative correlation between GH and TNF α. The aim of this study is to explore the relationship between endogenous GH secretion and certain pro and anti-inflammatory cytokines in short children undergoing GH stimulation testing for evaluation for GH deficiency. Methods: Plasma growth hormone, TNF α, CRP, IL-6, IL1-β, IL-4 and IL-10 levels are obtained at baseline and every 30 minutes for 150 minutes following two provocative agents (clonidine, and either arginine or glucagon). Results: Among the 23 children, 7 are found to be GH deficient. No significant differences in baseline TNF α levels are found between GH deficient and GH sufficient children. No correlation is identified between TNF α levels and GH levels during stimulation testing. Furthermore, no relationship is found between GH and pro-inflammatory cytokines or GH and anti-inflammatory cytokines. Conclusion: Our results do not demonstrate an acute relationship between endogenous GH secretion and the cytokines examined.
基金the Medical and Health Research Foundation of PLA,No.98Q015
文摘INTRODUCTIONCurrently the major treatment choices for shortbowel syndrome are parenteral nutrition and smallbowel transplantation.Both therapies involvegreat fiscal challenge and recurring complications.Recent years have witnessed the promisingexperimental results of pharmacologicalrehabilitation of remnant small bowel.
文摘Oxidative stress has been involved in neurodegenerative diseases. The growth hormone (GH) counteracts the levels of reactive oxygen species. Previously, we showed that the prolonged exposure to ozone causes oxidative stress in the hippocampus and memory deficits. In this work, we analyzed the effects of the growth hormone on the memory deficit generated by ozone exposure, growth hormone effects on the Insulin-like growth factor I (IGF-I), and the serinethreonine protein kinase (Akt) activation in the dentate gyrus. Our results show that GH prevents memory deficits in early stages of the neurodegenerative process.
文摘BACKGROUND The incidence of short stature in KBG syndrome is relatively high.Data on the therapeutic effects of growth hormone(GH)on children with KBG syndrome accompanied by short stature in the previous literature has not been summarized.CASE SUMMARY Here we studied a girl with KBG syndrome and collected the data of children with KBG syndrome accompanied by short stature from previous studies before and after GH therapy.The girl was referred to our department because of short stature.Physical examination revealed mild dysmorphic features.The peak GH responses to arginine and clonidine were 6.22 and 5.40 ng/mL,respectively.The level of insulin-like growth factor 1(IGF-1)was 42.0 ng/mL.Genetic analysis showed a c.2635 dupG(p.Glu879fs)mutation in the ANKRD11 gene.She received GH therapy.During the first year of GH therapy,her height increased by 0.92 standard deviation score(SDS).Her height increased from-1.95 SDS to-0.70 SDS after two years of GH therapy.There were ten children with KBG syndrome accompanied by short stature who received GH therapy in reported cases.Height SDS was improved in nine(9/10)of them.The mean height SDS in five children with KBG syndrome accompanied by short stature increased from-2.72±0.44 to-1.95±0.57 after the first year of GH therapy(P=0.001).There were no adverse reactions reported after GH treatment.CONCLUSION GH treatment is effective in our girl and most children with KBG syndrome accompanied by short stature during the first year of therapy.
文摘BACKGROUND With the improvement of economy and living standards,the attention paid to short stature in children has been increasingly highlighted.Numerous causes can lead to short stature in children,among which growth hormone deficiency(GHD)is a significant factor.AIM To investigate the long-term efficacy and safety of different doses of long-acting polyethylene glycol recombinant human growth hormone(PEG-rhGH)in the treatment of GHD in children.METHODS We selected 44 pediatric patients diagnosed with GHD who were treated at Wuhu First People's Hospital from 2014 to 2018.Total 23 patients were administered a high dose of long-acting PEG-rhGH at 0.2 mg/kg subcutaneously each week,forming the high-dose group.Meanwhile,21 patients were given a lower dose of long-acting PEG-rhGH at 0.14 mg/kg subcutaneously each week,establishing the low-dose Group.The total treatment period was 2 years,during which we monitored the patients’height,annual growth velocity(GV),height standard deviation score(HtSDS),chronological age(CA),bone age(BA),and serum levels of insulin-like growth factor-1(IGF-1)and insulin-like growth factor-binding protein-3(IGFBP-3)before treatment and at 6 mo,1 year,and 2 years after treatment initiation.We also monitored thyroid function,fasting plasma glucose,fasting insulin,and other side effects.Furthermore,we calculated the homeostatic model assessment for insulin resistance.RESULTS After 1 year of treatment,the GV,HtSDS,IGF-1,BA,and IGFBP-3 in both groups significantly improved compared to the pre-treatment levels(P<0.05).Moreover,when comparing GV,HtSDS,IGF-1,BA,and IGFBP-3 between the two groups,there were no statistically significant differences either before or after the treatment(P>0.05).During the treatment intervals of 0-1.0 years and 1.0-2.0 years,both patient groups experienced a slowdown in GV and a decline in HtSDS improvement(P<0.05).CONCLUSION The use of PEG-rhGH in treating GHD patients was confirmed to be effective,with similar outcomes observed in both the high-dose group and low-dose groups,and no significant differences in the main side effects.
文摘Aim: To study effects of recombinant human growth hormone (rhGH) on growth hormone-insulin-like growth factor axis (GH-IGFs) of human gastric cancer cell in vivo in order to reveal part mechanism of growth effects of rhGH on gastric cancer. Methods: Nude mice were randomly divided into control group, cisplatin (DDP) group, rhGH group and DDP + rhGH group after human gastric cancer xenograft model of node mice was successfully founded and drugs were used for 6 days. We investigated volume of tumor, inhibitory rate of tumor and cell cycle by slide gauge and flow cytometry. In addition, We also respectively investigated insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) of blood serum of nude mice, IGF-ImRNA, insulin-like growth factor-I receptor (IGF-IR) mRNA and IGFBP-3 mRNA of xenograft of nude mice by enzyme linked immunosorbent assay (ELISA) and semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) on the first day of completing use of drugs later. Results: Tumor grew obviously slowly and tumor inhibitory rate obviously rose in DDP group and DDP + rhGH group compared with control group and rhGH group (p p p < 0.05). Expressions of IGF-I mRNA and IGF-IR mRNA were not obviously different in all groups. But expression of IGFBP-3 mRNA obviously increased in rhGH group, DDP group and DDP + rhGH group compared with control group;meanwhile, expression of IGFBP-3 mRNA also obviously increased in DDP + rhGH group compared with control group, DDP group and rhGH group. Conclusion: Our results indicated rhGH in short-time use did not improve proliferation of human gastric cancer cells and its mechanism was possible that rhGH in short-time use raised simultaneously IGF-I and IGFBP-3 of blood serum and increased IGFBP-3 mRNA, but degraded ratio of IGF-I and IGFBP-3 of blood serum in human gastric cancer cells.
文摘Objective:To study the protective effect of perioperative recombinant human growth hormone (r-hGH) application on intestinal mucosal barrier function in patients with intestinal obstruction and the influence on the immune inflammatory response.Methods:60 patients with intestinal obstruction who underwent surgical treatment in our hospital between February 2013 and July 2016 were selected as the research subjects and divided into the control group (n=34) who received conventional surgical treatment and the observation group (n=26) who received surgery combined with perioperative r-hGH treatment. The serum levels of intestinal mucosal barrier indexes, immunoglobulin and inflammatory response indicators were compared between two groups of patients before and after treatment.Results: Before treatment, differences in serum levels of intestinal mucosal barrier indexes, immunoglobulin and inflammatory response indicators were not statistically significant between the two groups of patients. After treatment, serum intestinal mucosal barrier indexes Endotoxin, D-Lactate and DAO levels in observation group were lower than those in control group, immunoglobulin IgA, IgM and IgG levels were higher than those in control group, and inflammatory response indicators IL-1, IL-6, PCT and TNF-α levels were lower than those in control group patients. Conclusion:Perioperative r-hGH application in patients with intestinal obstruction can protect the intestinal mucosal barrier, also optimize the humoral immunity and suppress the systemic inflammatory response.
文摘AIM:To determine the effects of RNAi-mediated inhibition of the growth hormone receptor(GHR)gene on tumors and colon cancer cells in vivo.METHODS:Construction of a eukaryotic vector for human GHR expression,the pcDNA 6.2-GW/EmGFPsmall interfering RNAs(siRNAs)-GHR plasmid,was used to inhibit GHR expression.Thirty-six BALB/c nude mice were randomly divided into groups and treated with normal saline(NS),recombinant plasmid(G2),growth hormone(GH),5-fluorouracil(FU),G2+FU or G2+FU+GH.Each nude mouse was subcutaneously inoculated with 1×107human colon cancer SW480 cells;the nude mice were weighed before inoculation and on the 2nd,5th,8th,11th,14thand 17thday after inoculation.All nude mice were sacrificed after 17 d.Each subcutaneous tumor was removed and studied.Tumor volume was measured on the 5th,8th,11th,14thand 17thday after inoculation.The expression of GHR protein in the tumor tissue was detected by Western blotting analysis,and the differences in GHR mRNA expression in the tumor tissue were detected by real-time quantitative reverse transcription-polymerase chain reaction.RESULTS:Compared to the control group,the weights of the inoculated nude mice on the 17thday after inoculation were:G2:21.60±0.71 g,GH:21.64±0.45 g,FU:18.94±0.47 g,FU+G2:19.40±0.60 g,G2+FU+GH:21.04±0.78 g vs NS:20.68±0.66 g,P<0.05;the tumor volumes after the subcutaneous inoculation were:G2:9.71±3.82 mm3,FU:11.54±2.42mm3,FU+G2:11.42±1.11 mm3,G2+FU+GH:10.47±1.02 mm3vs NS:116.81±10.61 mm3,P<0.05.Compared to the GH group,the tumor volumes were significantly decreased in the experimental groups.The GHR protein expression(G2:0.39±0.02,FU:0.40±0.02,FU+G2:0.38±0.01,G2+FU+GH:0.39±0.01 vs NS:0.94±0.02,P<0.05)and the GHR mRNA expression(G2:14.12±0.10,FU:15.15±0.44,FU+G2:16.46±0.27,G2+FU+GH:15.37±0.57 vs NS:12.63±0.14,P<0.05)were significantly decreased and increased,respectively,in the experimental groups.CONCLUSION:Inhibition of GHR in human colon cancer SW480 cells resulted in anti-tumor effects in nude mice.
文摘Growth Hormone （GH） is an important and powerful metabolic hormone that is secreted in a pulsatile pattern from cells in the anterior pituitary, influenced by several normal and pathophysiological conditions. Human GH was first isolated in the 1950s and human derived cadaveric GH was initially used to treat patients with GH deficiency. However, synthetic recombinant GH has been widely available since the mid-1980s and the advent of this recombi- nant GH boosted the abuse of GH as a doping agent. Doping with GH is a well-known problem among elite athletes and among people training at gyms, but is forbidden for both medical and ethical reasons. It is mainly the anabolic and, to some extent, the lipolytic effects of GH that is valued by its users. Even though GH＇ s rumour as an effective ergogenic drug among athletes, the effectiveness of GH as a single doping agent has been questioned during the last few years. There is a lack of scientific evidence that GH in supraphysiological doses has additional effects on muscle exercise performance other than those obtained from optimised training and diet itself. However, there might be synergistic effects if GH is combined with, for example, anabolic steroids, and GH seems to have positive effect on collagen synthesis. Regardless of whether or not GH doping is effective, there is a need for a reliable test method to detect GH doping. Several issues have made the development of a method for detecting GH doping complicated but a method has been presented and used in the Olympics in Athens and Turin. A problem with the method used, is the short time span （24-36 hours） from the last GH administration during which the test effectively can reveal doping. Therefore, out-of-competition testing will be crucial. However, work with different approaches to develop an alternative, reliable test is ongoing.
基金the Key Project of ‘Blue Granary Science and Technology Innovation’ of the Ministry of Science and Technology (No. SQ2018 YFD090006)the National Natural Science Foundation of China (Nos. 31702326 and 41706174)+8 种基金the Natural Science Foundation of Guangdong Province (Nos. 2016A03 0313743, 2017A030313101 and 2018B030311050)the Department of Education of Guangdong Province (Nos. 2018KTSCX090 and 2018KQNCX106)the Guangdong Provincial Special Fund For Modern Agriculture Industry Technology Innovation Teams (No. 2019KJ149)the Zhanjiang Science and Technology Bureau (No. 2016A03017)Guangdong Ocean University Natural Science Research Program (2015 and 2016)the Project of Provincial Key Platform and Major Scientific Research of Colleges and Universities in Guangdong (No. 2015KTSCX058)the Sail Projects of Guangdong (2014.1)the Marine Fishery Science and Technology Extension Projects of Guangdong (Nos. A201408A06 and A201608B01)the Program for Scientific Research Start-Up Funds of Guangdong Ocean University
文摘The teleost Scatophagus argus is a species whose females grows faster than males.Growth hormone(gh)mRNA abundance in females pituitary is higher than that in males;however the mechanism underlining such differential is still unknown.Growth hormone(GH)is tightly associated with GH-releasing hormone(Ghrh)in vertebrates.In this study,Ghrh gene(ghrh)and its receptor gene,ghrhr,were isolated from S.argus.Tissue expression analysis showed that ghrh and ghrhr were mainly expressed in hypothalamus while ghrhr was expressed in pituitary and gh was predominantly expressed in pituitary.Twenty cultured S.argus individuals were used to compare ghrh,ghrhr and gh mRNA abundances,120 g and 181 g average weight for male(n=11)and female(n=9),respectively.Real-time PCR indicated that the ghrh and ghrhr mRNA abundances in male hypothalamus were significantly higher than those in female hypothalamus while that of gh mRNA abundance was significantly higher in female pituitary than in male pituitary.The ghrh and ghrhr mRNA abundances were significantly up-regulated in female hypothalamus 3 h after injection of 0.1 mg kg^-1 body weight Ghrh while pituitary ghrhr and gh mRNA abundances were not affected.In female hypothalamus,ghrh and ghrhr m RNA abundances were not affected at 6 h post-injection of 4 mg kg^-1 body weight 17α-methyltes-tosterone(17α-MT)or 17β-Estradiol(E2).In female pituitary,ghrhr m RNA abundance was down-regulated by 17α-MT while that of gh m RNA abundance was up-regulated by E2.Our findings indicated that E2,rather than Ghrh,plays an important role in up-regulating the expression of gh in female S.argus,which should aid to understand the sexual dimorphism of teleost growth.
文摘Extrahepatic biliary obstruction promotes intestinal translocation of bacteria and endotoxin and this process is an important cause of morbidity and mortality in patients with jaundice. This study was undertaken to investigate the effect and mechanism of recombinant human growth hormone (rhGH) and to alleviate intestinal translocation of bacteria and endotoxin in murine obstructive jaundice. METHODS:A group of 42 Wistar rats were divided into 3 groups:sham operation (SO), bile duct ligation (BDL), and BDL and rhGH treatment (rhGH). By the end of the experiment,on day 7, the animals were killed, and their liver function and serum endotoxin were measured, bacterial cultures of the liver, kidney and mesenchymal lymph were made. Terminal ileum mucosa was observed under an electron microscope. RESULTS:Liver function was improved more significantly in the rhGH group than in the BDL group. The value of endotoxin in the rhGH group was 0.38±0.03 EU/ml, significantly lower than that in the BDL group (0.65±0.04 EU/ml, P【0.01), and similar to that in the SO group (0.30±0.02 EU/ml, P】0.05). The rate of bacteria translocation in the liver, kidney and mesenteric lymph was much higher in the BDL group than in other two groups. The rate of bacteria translocation in mesenteric lymph was 64.29%,significantly higher than that in the SO group and the rhGH group (P【0.05). There was no significant difference in bacteria translocation rate between the SO group and the rhGH group (P】0.05). Under an electron microscope , ileum mucosa epithelial cells in the BDL group were necrotic, and organelle were markedly metamorphic. In the rhGH group, ultrastructural changes were less evident or similar to those in the SO group. CONCLUSION:rhGH has significant protective effects on intestinal mucosa barrier in obstructive jaundice, and reduces intestinal translocation of bacteria and endotoxin.
文摘Growth hormone(GH)excess is associated with several systemic complications,one of which is the increased risk of neoplastic processes particularly of the gastrointestinal(GI)tract.Among the GI neoplasms,the most reported association is with benign and malignant neoplasms of the colon.In the majority of published literature,an increased incidence of GI neoplasms,both colonic adenomas as well as colorectal carcinoma is reported.However,the studies on colon cancer-specific mortality rate are conflicting with recent studies reporting similar cancer-specific mortality rates in comparison to controls.Many studies have reported an association of colorectal neoplasms with GH levels.Pathogenic mechanisms put forward to explain this association of GH excess and GI neoplasms primarily involve the increased GH-insulin-like growth factor 1(IGF-1)signaling.Both GH and IGF-1 have proliferative,anti-apoptotic,and angiogenic effects on the systemic tissues leading to cellular proliferation.Other contributing factors to the increased risk of GI neoplasms include slow intestinal transit with a redundant large bowel,altered bile acids,deranged local immune response,shared genetic susceptibility factors and hyperinsulinemia.In view of the increased risk association,most guidelines for the care of acromegaly patients recommend an initial screening colonoscopy.Recommendations for further follow-up colonoscopy differ but broadly,the guidelines agree that it depends on the findings at first colonoscopy and state of remission of GH excess.Regarding the concern about the risk of colorectal cancers in patients receiving recombinant GH therapy,most cohort studies do not show an increased risk.
文摘AIM: To investigate whether the simultaneous treatment with human growth hormone (hGH) abolishes the negative effects of everolimus on anastomotic healing.METHODS: Forty-eight male Sprague-Dawley-rats were randomized to three groups of 16 animals each (I: vehicle; II: everolimus 3 mg/kg po; III: everolimus 3 mg/kg po + hGH 2.5 mg/kg sc). Animals were pre-treated with hGH and/or everolimus daily for seven days. Then a standard anastomosis was created in the descending colon and treatment was continued for another seven days. The anastomosis was resected in toto and the bursting pressure was assessed as a mechanical parameter of intestinal healing. Moreover, biochemical (Hydroxyproline, PCNA, MPO, MMP-2 and MMP-9) and histological (cell density, angiogenesis, amount of granulation tissue) parameters of intestinal healing were assessed.RESULTS: Anastomotic bursting pressure was significantly reduced by everolimus and a simultaneous treatment with hGH resulted in considerably higher values (I: 134 ± 19 mmHg, II: 85 ± 25 mmHg, III: 114 ± 25 mmHg; P < 0.05, I vs II; P = 0.09, I vs III and II vs III) Hydroxyproline concentration was significantly increased by hGH compared to everolimus alone (I: 14.9 ± 2.5 μg/mg, II: 8.9 ± 3.6 μg/mg, III: 11.9 ± 2.8 μg/mg; P < 0.05, I vs II/III and II vs III). The number of MPO-positive cells was reduced significantly by hGH compared to everolimus alone (I: 10 ± 1 n/mm², II: 15 ± 3 n/mm², III: 9 ± 2 n/mm²; P < 0.05, I vs II and II vs III), while the number of PCNA-positive cells were increased by hGH (I: 28 ± 3 /mm², II: 12 ± 3 /mm², III: 26 ± 12 /mm²; P < 0.05, I vs II and II vs III). Corresponding to these biochemical findings, HE-histology revealed significantly increased amount of granulation tissue in hGH-treated animals.CONCLUSION: Inhibition of intestinal wound healing by everolimus is partially neutralized by simultaeous treatment with hGH. Both inflammation as well as collagen deposition is influenced by hGH.
