OBJECTIVES: To investigate the changes in the serum levels of Klotho, fibroblast growth factor 23 (FGF23), and insulin-like growth factor-1 (IGF-1) in children with idiopathic short stature (ISS) before and after recombinant human growth hormone (rhGH) treatment, as well as the correlation of Klotho and FGF23 with the growth hormone (GH)/IGF-1 growth axis in these children. METHODS: A prospective study was conducted on 33 children who were diagnosed with ISS in the Department of Pediatrics, Hebei Provincial People's Hospital, from March 10, 2021 to December 1, 2022 (ISS group). Twenty-nine healthy children, matched for age and sex, who attended the Department of Child Healthcare during the same period, were enrolled as the healthy control group. The children in the ISS group were treated with rhGH, and the serum levels of Klotho, FGF23, and IGF-1 were measured before treatment and after 3, 6, and 9 months of treatment. A correlation analysis was conducted on these indexes. RESULTS: There were no significant differences in the serum levels of IGF-1, Klotho, and FGF23 between the ISS and healthy control groups (P>0.05). The serum levels of Klotho, FGF23, and IGF-1 increased significantly in the ISS group after 3, 6, and 9 months of rhGH treatment (P<0.05). In the ISS group, Klotho and FGF23 levels were positively correlated with the phosphate level before treatment (P<0.05). Before treatment and after 3, 6, and 9 months of rhGH treatment, the Klotho level was positively correlated with the IGF-1 level (P<0.05), the FGF23 level was positively correlated with the IGF-1 level (P<0.05), and the Klotho level was positively correlated with the FGF23 level (P<0.05), while Klotho and FGF23 levels were not correlated with the height standard deviation of point (P>0.05). CONCLUSIONS The rhGH treatment can upregulate the levels of Klotho, FGF23, and IGF-1 and realize the catch-up growth in children with ISS. Klotho and FGF23 may not directly promote the linear growth of children with ISS, but may have indirect effects through the pathways such as IGF-1 and phosphate metabolism. The consistent changes in Klotho, FGF23 and IGF-1 levels show that there is a synergistic relationship among them in regulating the linear growth of ISS children.
Child ; Humans ; Human Growth Hormone/pharmacology* ; Insulin-Like Growth Factor I/pharmacology* ; Fibroblast Growth Factor-23 ; Prospective Studies ; Growth Disorders ; Phosphates/pharmacology* ; Body Height

OBJECTIVETo investigate the effects of recombinant human growth hormone on serum lipid in aged male patients with chronic heart failure (CHF).

METHODSEighty seven patients with chronic heart failure(> or = 60 years old) were randomly divided into 2 groups: the CHF control group (n = 46) who received regular therapy and the CHF experimental group (n = 41) who received regular therapy and recombinant human growth hormone. The treatment would be continued for 3 months. Another group was normal control group (n = 10). The detection of serum growth hormone (GH), insulin-like growth factor (IGF-1), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) was carried out before and after treatment in the participants.

RESULTSBefore treatment, the levels of GH and IGF-1 were not significantly different among groups. After treatment, the levels of GH (0.71 +/- 0.34 vs 0.96 +/- 0.48) and IGF-1 (95.64 +/- 21.11 vs 111.64 +/- 23.14)in CHF experimental group were higher than those before the treatment. In CHF control group, the levels of GH(0.81 +/- 0.32 vs 0.79 +/- 0.29) and IGF-1 (97.82 +/- 19.74 vs 99.65 +/- 20.11) had no significant change after the treatment. After treatment, the levels of GH (0.96 +/- 0.48 vs 0.79 +/- 0.29) and IGF-1 (111.64 +/- 23.14 vs 99.65 +/- 20.11) in CHF experimental group were higher compared with that of CHF control group. Before treatment, the serum levels of LDL-C, HDL-C, TC and TG had no significant difference among groups. After treatment,the levels of LDL-C (2.11 +/- 0.82 vs 1.76 +/- 0.51) and TC (3.78 +/- 1.34 vs 3.21 +/- 1.17) in CHF experimental group were lower than those before the treatment. However, the levels of HDL-C (1.10 +/- 0.31 vs 0.99 +/- 0.28)and TG (1. 89 +/- 1.07 vs 1.66 +/- 0.95) had no significant change after the treatment compared with before treatment. In CHF control group, the serum lipid levels had no significant change after the treatment.

CONCLUSIONAs the treatment of rhGH for aged male patients with chronic heart failure, GH influences lipid metabolism, which reduces the level of LDL-C, TC. However GH has no effects on the serum HDL-C and TG level. With the treatment of rhGH for long-term, lipid metabolism should be paid attention,and the treatment for blood lipid reduction should be adjusted in time.

Aged ; Chronic Disease ; Heart Failure ; blood ; therapy ; Human Growth Hormone ; pharmacology ; Humans ; Lipids ; blood ; Male ; Recombinant Proteins ; pharmacology

OBJECTIVETo determine the effect of gonadotropin releasing hormone agonist (GnRHa), by itself alone or in combination with recombinant human growth hormone (rhGH), on height in young girls (bone age≥10 years) with idiopathic central precocious puberty (ICPP).

METHODSEighty girls with ICPP (9.0±0.7 years old) from six medical centers across Southeast and Southwest China participated in this study. They were allocated to treatment with GnRHa+rhGH (n=31) and GnRHa (n=49) respectively. Girls in the GnRHa+rhGH group (bone age 11.18 ±0.53 years) were treated with GnRHa for 25.29±6.92 months and rhGH for 12.87±7.02 months. Girls in the GnRHa group (bone age 11.03 ±0.50 years) were treated with GnRHa for 25.96±8.95 months. The height standard deviation for bone age (HtSDS-BA), predicted adult height, near-adult height and net height increase before and after treatment were recorded for girls in both groups.

RESULTSHtSDS-BA was significantly improved after treatment for both groups (P<0.01) and the HtSDS-BA value was superior in the GnRHa+rhGH group over the GnRHa group (P<0.01). Values in near adult height (157±6 cm vs 157±4 cm), net height increase after treatment (4.68 cm vs 3.89 cm), and predicted adult height after drug withdrawal (161±5 cm vs 158±5 cm) were higher in the GnRHa+rhGH group than the GnRHa group, but the differences were not significant.

CONCLUSIONSBoth GnRHa plus rhGH and GnRHa alone can improve the near adult height in girls with ICPP with a bone age ≥10 years to a similar extent. Adult height predicted based on bone age in ICPP girls following drug withdrawal is usually overestimated and precautions should be taken when this parameter is used.

Body Height ; drug effects ; Child ; Female ; Gonadotropin-Releasing Hormone ; analogs & derivatives ; pharmacology ; Human Growth Hormone ; pharmacology ; Humans ; Puberty, Precocious ; drug therapy ; physiopathology

To investigate the effect of recombinant human growth hormone (rhGH) on JAK2-STAT3 pathway and the growth of gastric cancer cell lines at different GHR expression status, the eukaryotic expression vector targeting human GHR (pGPU6/GFP/Neo-shGHR and pGPU6/GFP/Neo-scramble) was constructed and transfected into MGC803 cells by Lipofectamine 2000. Stable expressive cell lines were obtained by G418 screening. The expression of GHR was analyzed by Western blotting. After being stimulated with rhGH, cell growth was detected by MTT assay. Cell cycle and apoptosis were examined by flow cytometry. The components of JAK2/STAT3 signaling pathway were detected by Western blotting. There is no significant difference of GHR expression between MGC803 and pGPU6/GFP/Neo-scramble-transfected cells (named as MGC803-NC) (P > 0.05). Compared with MGC803, the GHR expression in pGPU6/GFP/Neo-shGHR-transfected cells (named as MGC803-shGHR) decreased significantly (protein decreased 50%). The cells were treated with rhGH at 0, 150 and 300 ng x mL(-1), the growth rate of MGC803 and MGC803-NC increased significantly, PI and the number of G2/M phase cells all increased significantly, and apoptosis decreased significantly. Western blotting revealed that the expression of pJAK2 and pSTAT3 was up-regulated after being treated with rhGH in MGC803 and MGC803-NC cells. In contrast, similar change was not observed in MGC803-shGHR cells. Knockdown of GHR gene may decrease the sensitivity of gastric cancer cells to rhGH, and down-regulating of components of the expression of JAK2/STAT3 signaling pathway may be the potential mechanisms.
Apoptosis ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; Down-Regulation ; Human Growth Hormone ; genetics ; pharmacology ; Humans ; Janus Kinase 2 ; metabolism ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Receptors, Somatotropin ; genetics ; metabolism ; Recombinant Proteins ; genetics ; pharmacology ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; Stomach Neoplasms ; metabolism ; pathology ; Transfection

OBJECTIVETo study the expression of perforin and granzyme B (GzmB) in the lungs of asthmatic rats and the effect of recombinant human growth hormone (rhGH) on the expression.

METHODSThirty Sprague-Dawley male rats were randomly divided into a normal control group and asthma groups with and without rhGH treatment. An asthma model was prepared by repeated sensitization with ovalbumin and aluminium hydroxide. The morphological changes of the airway were observed by hematoxylin and eosin staining. Terminal deoxyribonucleotide transferase-mediated Dutp-bintin (TUNLE) was used to detect the apoptosis of epithelial cells in the airway. RT-PCR was used to detect the mRNA transcripts of perforin and GzmB in the lung tissues.

RESULTSA significantly increased apoptosis rate of airway epithelial cells was noted in the untreated asthma group. The apoptosis rate was significantly ruduced in the rhGH-treated asthma group (P<0.05). Compared with the control group, perforin and GzmB expression in the lungs in the untreated asthma group increased significantly. The rhGH-treated asthma group demonstrated significantly decreased perforin (0.48 ± 0.08 vs 0.63 ± 0.08; P<0.05) and GzmB (0.44 ± 0.13 vs 0.71 ± 0.15; P<0.05) expression in the lungs compared with the untreated asthma group. Both PFP (r=0.800, P<0.05) and GzmB (r=0.806, P<0.01) were positively correlated with the apoptosis rate of airway epithelial cells.

CONCLUSIONSPerforin and GzmB may play important roles in the pathogenesis of asthma. rhGH treatment can inhibit apoptosis of airway epithelial cells and airway remodeling, possibly through a reduction in perforin and GzmB expression.

Animals ; Apoptosis ; Asthma ; metabolism ; Bronchi ; pathology ; Granzymes ; analysis ; genetics ; Human Growth Hormone ; pharmacology ; Male ; Pore Forming Cytotoxic Proteins ; analysis ; genetics ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley

Human Growth Hormone ; administration & dosage ; pharmacology ; Recombinant Proteins ; administration & dosage ; pharmacology

OBJECTIVETo investigate the effect of Thymosin and growth hormone(GH) on inflammatory response in burn rats or burn rats with sepsis.

METHODSSixty-four SD rats were randomly divided into normal control group (NC, without treatment), sepsis group (S, with injection of LPS), sepsis + Thymosin group (ST, with successive injection of Thymosin and LPS), sepsis + GH group [SGH, with successive injection of recombinant human GH (rhGH) and LPS], burn group, burn + sepsis group (BS, with injection of LPS after burn), burn + sepsis + Thymosin group (BST, with successive injection of Thymosin and LPS after burn), burn + sepsis + GH (BSGH, with successive injection of rhGH and LPS after burn), with 8 rats in each group. Specimens of spleen tissues were harvested to determine HLA-DR in lymphocyte and evaluate inflammatory cell infiltration (score). Specimens of peripheral blood were collected to determine Toll-like receptor 4 (TLR4) level in monocyte and serum level of TNF-alpha, IL-4, IL-6, IL-10.

RESULTSCompared with those in NC group, serum level of IL-10 in S group decreased obviously, while other indices increased obviously (P < 0.01). The levels of HLA-DR and TLR4 and serum level of TNF-alpha were similar between SGH and ST groups (P > 0.05). Compared with those in SGH group [(2.87 +/- 0.04) score, and IL-6 (0.0083 +/- 0.0018) microg/mg, IL-4 (0.0102 +/- 0.0021) microg/mg, IL-10 (0.0310 +/- 0.0027) microg/mg, respectively], degree of inflammatory cell infiltration (1.50 +/- 0.76) score and serum levels of IL-6, IL-4, IL-10 of rats in ST group decreased obviously (0.0064 +/- 0.0012, 0.0058 +/- 0.0024, 0.0230 +/- 0.0021 microg/mg, respectively, P < 0.01). The levels of HLA-DR, TLR4 and inflammatory cell infiltration degree of spleen in B group were respectively higher than those in NC group and lower than those in BS group. Compared with those in NC group, serum levels of TNF-alpha, IL-6 in B group increased significantly, while IL-4, IL-10 showed an opposite tendency. There was no obvious difference between BST and BSGH groups in serum levels of HLA-DR and IL-6 (P > 0.05). Compared with those in BST group, inflammatory cell infiltration degree in spleen and the levels of TLR, TNF-alpha obviously decreased (P < 0.01), while IL-4 and IL-10 levels increased in BSGH group (P < 0.01).

CONCLUSIONSInhibitive effects between Thymosin and GH on extensive inflammatory reaction were similar with or without trauma, and GH has better effect as compared with Thymosin when with trauma.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Burns ; immunology ; Human Growth Hormone ; pharmacology ; Inflammation ; immunology ; Male ; Rats ; Rats, Sprague-Dawley ; Sepsis ; immunology ; Thymosin ; pharmacology

This study was designed to examine the effects of recombinant human growth hormone replacement on somatic growth and cognitive function in hypophysectomized (HYPOX) female Sprague-Dawley rats. Rats (5 per group) were randomized by weight to 3 experimental groups: group 1, administered 200 microgram/kg of GH once daily for 9 days; group 2, administered 200 microgram/kg of GH twice daily; and group 3, administered saline daily. Somatic growth was evaluated by measurement of body weight daily and of the width of the proximal tibial growth plate of the HYPOX rats. Cognitive function was evaluated using the Morris water maze (MWM) test. The results indicated that GH replacement therapy in HYPOX rats promoted an increase in the body weight and the width of the tibial growth plate in a dose-dependent manner. On the third day of the MWM test, the escape latency in the GH-treated groups 1 and 2 was significantly shorter than that in the control rats (P<0.001 and P=0.032, respectively), suggesting that rhGH improved spatial memory acquisition in the MWM test. Therefore it is concluded that rhGH replacement therapy in HYPOX rats stimulates an increase in somatic growth in a dose-dependent manner and also has beneficial effects on cognitive functions.
Animals ; Body Weight ; Female ; Growth/*drug effects ; Growth Plate/drug effects/pathology ; Human Growth Hormone/administration & dosage/*pharmacology ; Humans ; *Hypophysectomy ; Rats ; Rats, Sprague-Dawley ; Spatial Behavior/*drug effects

OBJECTIVETo investigate the role of recombinant human growth hormone (rhGH) in the growth of Bel-7402 human hepatic carcinoma cell line (Bel-7402 line) in vitro and its effects on GHR expression.

METHODSTumor cell count, MT assay and colony forming test were performed to determine the responses of Bel-7402 to different concentrations of rhGH (0, 1, 10, 100, 1000, 10 000 ng/ml). Metabolism of DNA in tumor cells was analyzed with the method of mixture of 3H-TdR. Radioreceptor assay was used to detect the GHR expression of the hepatic carcinoma cell lines and its relation to different rhGH concentrations.

RESULTSrhGH accelerated the proliferation of the Bel-7402 line when the concentration of rhGH was over 100 ng/ml (P < 0.05). Other rhGH concentrations had also positive effects, but with reduced effect as compared with that of 100 ng/ml. After 24 h of rhGH addition of concentration of 10 ng/ml and 100 ng/ml, GHR site number was significantly higher than that in control group, while the 10,000 ng/ml group showed a significantly lower GHR site number.

CONCLUSIONSDifferent concentrations of rhGH might result in variable effects on the growth of Bel-7402 hepatic carcinoma cell line. Certain concentrations of rhGH might stimulate the growth of the cell line. rhGH can regulate the expression of GHR in the cell line.

Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Human Growth Hormone ; pharmacology ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Receptors, Somatotropin ; genetics ; metabolism

OBJECTIVENumerous studies in children with growth hormone deficiency (GHD) show that recombinant human growth hormone (rhGH) treatment results in significant catch-up growth, but some papers reported that the children who underwent rhGH therapy might be at increased risk of diabetes. The aim of this study was to investigate the effects of rhGH treatment on blood glucose and insulin metabolism in children with GHD and the relationship between growth hormone (GH) and glucose homeostasis.

METHODSIn this study, 44 children with GHD treated with rhGH [0.1 U/(kgxd)] and age- and sex-matched 20 healthy children were enrolled. The GHD group included 28 males and 16 females aged from 4.5 to 16.5 years (mean 10.4 +/- 2.6 years), including 18 cases of complete GHD and 26 cases of partial GHD. The sexual development stage of all subjects was in Tanner I. Oral glucose tolerance tests (OGTT) were done, and body mass index (BMI), serum insulin-like growth factor-1 (IGF-1) level and insulin resistance by homeostasis model (HOMA-IR) were measured at the time of diagnosis and every 3 months after rhGH therapy. Continuous glucose monitoring system (CGMS) was applied for two cases with hyperglycemia.

RESULTS(1) Fasting glucose and IGF-1 levels increased since 3 months of treatment and did not decrease since then. The levels of fasting glucose and IGF-1 at every time points of rhGH therapy were higher than the levels at the time of diagnosis (F = 6.81, P < 0.01; F = 7.31, P < 0.01, respectively). HOMA-IR and fasting insulin levels were increased since 3 and 9 months of treatment (P = 0.001 and P = 0.021, respectively). They decreased after 12 months of therapy and the levels at 18 months of therapy were similar to that at diagnosis. (2) Pearson correlation analysis showed that HOMA-IR was positively correlated with BMI, IGF-1 and the duration of treatment (r = 0.251, 0.437, 0.281, P < 0.01, respectively). The curve between HOMA-IR and duration of therapy was similar with parabola and the quadratic equation obtained was as follows: HOMA-IR = 1.5048 + 0.2177 x duration of therapy (months)-0.0103 x duration of therapy (months)(2) (r(2) = 0.147, F = 14.16, P < 0.01). (3) Two cases had transitory hyperglycemia. Their fasting glucose levels were all higher than 7.1 mmol/L. The glucose levels returned to normal after 1 month and 5 days respectively. OGTT and CGMS showed that their plasma glucose levels were normal after rhGH therapy was applied again.

CONCLUSIONThe children who underwent rhGH therapy may be at increased risk of insulin resistance (especially during the first year) and the therapy may even induce transitory glucose metabolic disorder in a very small proportion of patients. Circulating IGF-1 may participate in the control of insulin sensitivity and play an important role in the hormonal balance between GH and insulin. It may be necessary to monitor glucose metabolism and IGF-1 for all children who are treated with rhGH therapy.

Adolescent ; Blood Glucose ; drug effects ; metabolism ; Body Mass Index ; Case-Control Studies ; Child ; Child, Preschool ; Energy Metabolism ; drug effects ; Female ; Follow-Up Studies ; Glucose ; metabolism ; Glucose Tolerance Test ; Growth Disorders ; drug therapy ; etiology ; metabolism ; Homeostasis ; drug effects ; Human Growth Hormone ; administration & dosage ; adverse effects ; deficiency ; pharmacology ; Humans ; Hyperglycemia ; chemically induced ; Insulin ; blood ; Insulin Resistance ; Insulin-Like Growth Factor I ; analysis ; Male ; Recombinant Proteins ; pharmacology ; Time Factors ; Treatment Outcome