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1.
Medicine (Baltimore) ; 99(19): e19855, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384430

RESUMO

The endoscopic endonasal transsphenoidal approach (EETA) is the primary treatment for growth hormone (GH) adenoma. This study aimed to investigate the outcomes of EETA in 33 patients with GH-secreting pituitary adenoma (PA).Thirty-three patients who underwent EETA in Eighth People's Hospital of Shenzhen between January 2013 and December 2017 were included in the comprehensive analysis. Factors affecting the extent of resection and postoperative remission rates were also reviewed.The total cut rate was 63.6% (21), and the total remission rate was 66.7% (22) in all patients after surgery. The cure rate was 60.6% (20) for 33 patients. The total removal rate and remission rate were significantly different (P = .01, P = .007) for microadenomas, macroadenomas, and giant adenomas. In addition, the total removal rate and remission rate were significantly different (P = .004, P = .007) for patients with noninvasive and invasive GH-secreting PAs. Furthermore, there were significant differences (P = .003, P = .005) in the total removal rate and remission rate of patients with different preoperative GH levels. All patients with hypertension and diabetes mellitus were normalized. Three patients exhibited recurrence after surgery. Several patients suffered from postoperative complications, including transient diabetes insipidus in 3 (9.1%) patients and postoperative transient cerebrospinal fluid leakage in 2 (6.1%) patients.EETA is an effective therapeutic approach for treating patients with GH-secreting PA with high remission and low complication rates. Therefore, EETA should be considered a primary treatment for patients with GH-secreting PA.


Assuntos
Adenoma/cirurgia , Endoscopia/métodos , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Nariz/cirurgia , Osso Esfenoide/cirurgia , Adulto , Idoso , Endoscopia/efeitos adversos , Feminino , Hormônio do Crescimento/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Período Pré-Operatório , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
2.
Wiad Lek ; 73(2): 266-271, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32248157

RESUMO

OBJECTIVE: The aim: to investigate the copper content in blood serum of children with different short stature types. PATIENTS AND METHODS: Materials and methods: In the first stage, a comprehensive survey of 258 school children aged 7-11 was carried out in Chernivtsi to assess the prevalence of short staturechildren of school-age. In the second stage, a comparative study of 42 children aged 3 to 15 years with different types of short stature was conducted. Research: anthropometry, determination of growth hormone, TSH, IGF-1, and copper level in blood plasma. RESULTS: Results: The largest growth rate in children with somatotropic insufficiency, the syndrome of a biologically inactive growth hormone ranged from 4.1 cm/year to 1.6 cm/year, the ones with a family constitutional low-growth - from 5.7 cm/year to 3.3 cm/year. In 57 cases, that makes 1% of children with short stature, the blood plasma level of copper made less and rated 0.89 ± 0.04 µg / ml, which is believed to be lower (pу0,001) the average copper in children of the control group - 1.07 ± 0.02 µg / ml. Indices of copper in blood plasma in children with somatotropic insufficiency were the lowest and averaged 0.75 ± 0.03 µg / l, p<0.05. CONCLUSION: Conclusions: The lack of copper in the blood plasma is observed in most children with short stature, which indicates the need for appropriate correction.


Assuntos
Cobre/sangue , Transtornos do Crescimento , Adolescente , Criança , Pré-Escolar , Hormônio do Crescimento , Hormônio do Crescimento Humano , Humanos , Prevalência
3.
Medicine (Baltimore) ; 99(16): e19813, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32311999

RESUMO

RATIONALE: Wiedemann-Steiner syndrome (WDSTS, online mendelian inheritance in man 605130) is a rare autosomal dominant disorder characterized by hypertrichosis cubiti. Here, we report a Chinese boy who do not show the characteristic of hypertrichosis cubiti, and was misdiagnosed as blepharophimosis-ptosis-epicanthus inversus syndrome at first. We found a de novo frameshift mutation (p.Glu390Lysfs*10) in the KMT2A gene, which was not reported before. Our study increases the cohort of Chinese WDSTS patients, and expand the WDSTS phenotypic and variation spectrum. PATIENT CONCERNS: The patient demonstrated typical craniofacial features of blepharophimosis-ptosis-epicanthus inversus syndrome, including small palpebral fissures, ptosis, telecanthus, and epicanthus inversus, besides he had congenital heart disease (ventricular septal defects), strabismus, hypotonia, amblyopia, delayed speech and language development, delayed psychomotor development, and amblyopia (HP:0000646) which was not reported before. DIAGNOSIS: FOXL2 gene was cloned and sequenced, however, there was no mutation detected in this patient. The result of Chromosomal microarray analysis was normal. The patient was diagnosed as WDSTS by whole exome sequencing. INTERVENTIONS: The patient received cardiac surgery, frontalis suspension and regular speech and occupational therapy. He also treated with growth hormone (GH). OUTCOMES: The patient's symptoms are improved after cardiac surgery and frontalis suspension, he can express himself well now and had a 10 cm gain in height. LESSONS: As the relationship between genotype and phenotype becomes more and more clear, WES is incredibly powerful tool to diagnose the disease of WDSTS.


Assuntos
Anormalidades Múltiplas/genética , Blefarofimose/diagnóstico , Contratura/genética , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/genética , Cardiopatias Congênitas/diagnóstico , Histona-Lisina N-Metiltransferase/genética , Hipertricose/congênito , Deficiência Intelectual/genética , Microcefalia/genética , Proteína de Leucina Linfoide-Mieloide/genética , Anormalidades da Pele/diagnóstico , Anormalidades Urogenitais/diagnóstico , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/terapia , Grupo com Ancestrais do Continente Asiático/genética , Criança , Contratura/diagnóstico , Contratura/terapia , Erros de Diagnóstico , Facies , Genótipo , Transtornos do Crescimento/etiologia , Transtornos do Crescimento/terapia , Hormônio do Crescimento/uso terapêutico , Cardiopatias Congênitas/cirurgia , Humanos , Hipertricose/diagnóstico , Hipertricose/etiologia , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/terapia , Masculino , Microcefalia/diagnóstico , Microcefalia/terapia , Mutação , Fenótipo , Resultado do Tratamento , Sequenciamento Completo do Exoma/métodos
4.
Yonsei Med J ; 61(4): 331-340, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32233176

RESUMO

PURPOSE: Osteoarthritis (OA) of the temporomandibular joint (TMJ) elicits cartilage and subchondral bone defects. Growth hormone (GH) promotes chondrocyte growth. The aim of this study was to evaluate the efficacy of intra-articular injections of GH to treat TMJ-OA. MATERIALS AND METHODS: Monosodium iodoacetate (MIA) was used to induce OA in the TMJs of rats. After confirming the induction of OA, recombinant human GH was injected into the articular cavities of rats. Concentrations of GH and IGF-1 were measured in the blood and synovial fluid, and OA grades of cartilage and subchondral bone degradation were recorded by histological examination and micro-computed tomography. RESULTS: MIA-induced OA in the rat TMJ upregulated insulin-like growth factor-1 (IGF-1) rather than GH levels. GH and IGF-1 concentrations were increased after local injection of GH, compared with controls. Locally injected GH lowered osteoarthritic scores in the cartilage and subchondral bone of the TMJ. CONCLUSION: Intra-articular injection of GH improved OA scores in rat TMJs in both cartilage and subchondral bone of the condyles without affecting condylar bone growth. These results suggest that intra-articular injection of human GH could be a suitable treatment option for TMJ-OA patients in the future.


Assuntos
Condrócitos/efeitos dos fármacos , Hormônio do Crescimento/administração & dosagem , Fator de Crescimento Insulin-Like I/administração & dosagem , Osteoartrite/tratamento farmacológico , Articulação Temporomandibular/efeitos dos fármacos , Idoso , Animais , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Hormônio do Crescimento/efeitos adversos , Hormônio do Crescimento Humano , Humanos , Injeções Intra-Articulares , Masculino , Osteoartrite/diagnóstico por imagem , Osteoartrite/patologia , Ratos , Líquido Sinovial , Articulação Temporomandibular/diagnóstico por imagem , Articulação Temporomandibular/fisiopatologia , Microtomografia por Raio-X
5.
Endocr Pract ; 26(3): 340-353, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32163313

RESUMO

Over the past few decades, there has been an unprecedented rise in off-label use and misuse of testosterone, growth hormone, thyroid hormone, and adrenal supplements. Testosterone therapy is often promoted to men for the treatment of low energy, lower libido, erectile dysfunction, and other symptoms. Growth hormone is used in attempts to improve athletic performance in athletes and to attenuate aging in older adults. Thyroid hormone and/or thyroid supplements or boosters are taken to treat fatigue, obesity, depression, cognitive impairment, impaired physical performance, and infertility. Adrenal supplements are used to treat common nonspecific symptoms due to "adrenal fatigue," an entity that has not been recognized as a legitimate medical diagnosis. Several factors have contributed to the surge in off-label use and misuse of these hormones and supplements: direct-to-consumer advertising, websites claiming to provide legitimate medical information, and for-profit facilities promoting therapies for men's health and anti-aging. The off-label use and misuse of hormones and supplements in individuals without an established endocrine diagnosis carries known and unknown risks. For example, the risks of growth hormone abuse in athletes and older adults are unknown due to a paucity of studies and because those who abuse this hormone often take supraphysiologic doses in sporadic intervals. In addition to the health risks, off-label use of these hormones and supplements generates billions of dollars of unnecessary costs to patients and to the overall health-care system. It is important that patients honestly disclose to their providers off-label hormone use, as it may affect their health and treatment plan. General medical practitioners and adult endocrinologists should be able to begin a discussion with their patients regarding the unfavorable balance between the risks and benefits associated with off-label use of testosterone, growth hormone, thyroid hormone, and adrenal supplements. Abbreviations: DHEA = dehydroepiandrosterone; FDA = U.S. Food and Drug Administration; GH = growth hormone; IGF-1 = insulin-like growth factor 1; LT3 = L-triiodothyronine; LT4 = levothyroxine; T3 = total triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone.


Assuntos
Uso Off-Label , Idoso , Hormônio do Crescimento , Humanos , Masculino , Testosterona , Hormônios Tireóideos , Tireotropina , Tiroxina , Tri-Iodotironina
6.
Zhonghua Shao Shang Za Zhi ; 36(2): 147-149, 2020 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-32114735

RESUMO

Diabetic foot ulcer is a common complication of diabetes mellitus and the main cause of disability and death of diabetic patients, which has become an international medical and health problem. In recent years, the clinical usage of growth hormone in the treatment of diabetic foot ulcer has achieved good results. This article reviews the relevant literature at home and abroad, and summarizes the possible efficacy and mechanism of growth hormone in the treatment of diabetic foot ulcers.


Assuntos
Pé Diabético , Hormônio do Crescimento , Humanos
7.
Eur J Paediatr Dent ; 21(1): 53-54, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32183529

RESUMO

BACKGROUND: Macrodontia is a rare dental anomaly, and isolated macrodontia is even more infrequent. The aim of this article is to report on a young male patient with macrodontia of the mandibular premolars. CASE REPORT: We herein present a case report of a young male patient receiving pharmacological growth hormone therapy for 10 years, who was diagnosed with macrodontia of the mandibular premolars. The patient underwent surgical treatment at the School of Dentistry of the University of Buenos Aires and was followed-up for more than 3 years. CONCLUSION: Macrodontia is a rare condition. Early diagnosis and treatment of this anomaly favors adequate formation of the dental arches. In the light of this case report, a review of paediatric patients who received growth hormone therapy during the tooth formation stage would seem relevant.


Assuntos
Hormônio do Crescimento , Anormalidades Dentárias , Dente Pré-Molar , Criança , Humanos , Masculino
8.
Pediatr Endocrinol Rev ; 17(Suppl 1): 191-197, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32208563

RESUMO

Both in vitro and in vivo experimental studies proved that insulin has an important anabolic role. This physiological function of insulin is reflected in its well documented involvement in protein metabolism and in acceleration of cell proliferation. Support for a growth promoting action of insulin is further provided by clinical studies that revealed that children with hypoinsulinemia have a decreased growth rate whereas, on the other hand, children with hyperinsulinemia have an accelerated growth. While it was initially assumed that the growth activities of insulin are facilitated via cross-talk with the closely related insulin-like growth factor-1 receptor (IGF-1R), it is now clear that the vast majority of these activities are mediated via direct interaction with the insulin receptor (IR). The present article provides an overview of the growth and proliferative actions of insulin, with an emphasis on a number of pathological conditions, including cancer.


Assuntos
Insulina/uso terapêutico , Hormônio do Crescimento , Hormônio do Crescimento Humano , Humanos , Fator de Crescimento Insulin-Like I , Receptor IGF Tipo 1
9.
Life Sci ; 253: 117581, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32209424

RESUMO

AIMS: Cisplatin (CDDP) is an effective antineoplastic agent, however, its serious nephrotoxicity limits therapeutic use. Human growth hormone (hGH) has proved antioxidant and anti-inflammatory activities. The present study aimed to investigate the nephroprotective effects of hGH against CDDP-induced nephrotoxicity and the mechanisms underlying this nephroprotection. MAIN METHODS: Male albino rats injected with CDDP (7 mg/kg) and nephrotoxicity indices, oxidative stress and inflammatory biomarkers (high mobility group box protein-1 (HMGB-1), soluble epoxide hydrolase (sEH), and nuclear factor-kappa B (NF-κB)) were assessed. Also, insulin-like growth factor-1 (IGF-1) and Nuclear factor-erythroid-2 (Nrf2)/heme oxygenase-1 (HO-1) pathway were assessed. KEY FINDINGS: hGH (1 mg/kg) improved kidney function and antioxidant systems and showed intact renal tubular epithelium. Cisplatin upregulated the HMGB-1/NF-κB and downregulated Nrf2/HO-1 pathways which were reversed by hGH and aligned with increased renal IGF-1 expression. Also, IGF-1/sEH crosstalk might be involved in hGH nephroprotection. Moreover, hGH downregulated HSP70 and caspase-3 expressions. SIGNIFICANCE: these results concluded that hGH can attenuate the inflammation and oxidative stress attained by CDDP probably through inhibition of Nrf2/HO-1 pathway. We also suggested that Keap1/Nrf2-mediated upregulation of the antioxidant HO-1 might inhibit HMGB-1/NF-κB signaling and thus provide the principal protection mechanism offered by hGH against CDDP-induced kidney injury.


Assuntos
Lesão Renal Aguda/prevenção & controle , Cisplatino/efeitos adversos , Hormônio do Crescimento/metabolismo , Heme Oxigenase-1/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/patologia , Animais , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/metabolismo , Antineoplásicos/efeitos adversos , Antineoplásicos/metabolismo , Antioxidantes/efeitos adversos , Antioxidantes/farmacologia , Caspase 3/metabolismo , Cisplatino/metabolismo , Modelos Animais de Doenças , Epóxido Hidrolases/metabolismo , Hormônio do Crescimento/farmacologia , Proteínas HMGB/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Hormônio do Crescimento Humano , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Transdução de Sinais
10.
Gene ; 737: 144456, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32044406

RESUMO

Somatotroph adenoma is the main cause of acromegaly which have peripheral signs with growth of soft tissues and multiple comorbidities. Surgery and adjuvant therapy with somatostatin analogs (SSA) fail in more than 25% of patients. PRDM2, a tumor suppressor, plays an important role in cancer and obesity, including pituitary adenomas. In this study, we analyze the correlation of PRDM2 and oncogene c-Myc in 70 somatotroph adenomas according immunohistochemical staining, furthermore, we probed that whether PRDM2 participates in c-Myc signaling pathway in vitro experiment. 70 somatotroph adenomas patients were divided into low patients and high patients according to median of H-score of PRDM2 or c-Myc. Low PRDM2 patients had higher risk of invasive behavior, larger tumor volume and recurrence chance than high PRDM2 group (P = 0.015, P = 0.031, P = 0.017). High c-Myc patients had higher risk of invasive behavior, larger tumor volume and recurrence chance than low c-Myc group (P = 0.012, P = 0.002, P = 0.015). It was a negative correlation between H-score of PRDM2 and c-Myc (PRDM2 = -0.163 × c-Myc + 67.11, r = -0.407). The ability of cell proliferation was declined in a time dependent manner after overexpression of PRDM2 (PRDM2 group) compared to that in control GH3 cells (P < 0.05). Through flow cytometry assay, PRDM2 could induce the apoptosis and G2/M arrest in GH3 cell (both p < 0.05). Transwell experiment proved less trans-membrane cells in PRDM2 group than those in control group (415 ± 76 vs 145 ± 37, P < 0.01). RT-PCR and western blot both proved PRDM2 could inhibit the level c-Myc and elevate the levels of CDKN1A and CDKN1B. Combined with c-Myc inhibitor 10058-F4, PRDM2 further inhibited cell proliferation and induced more apoptosis in GH3 cell. Taken together, we found that PRDM2 negatively regulated the expression of c-Myc in somatotroph adenomas, and testified the synergism between PRDM2 gene therapy and c-Myc inhibitor in vitro experiment.


Assuntos
Adenoma/genética , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Genes myc , Adenoma Hipofisário Secretor de Hormônio do Crescimento/genética , Histona-Lisina N-Metiltransferase/genética , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Adenoma/diagnóstico por imagem , Adenoma/patologia , Adulto , Ciclo Celular , Proliferação de Células , Feminino , Hormônio do Crescimento/metabolismo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico por imagem , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
11.
Zhonghua Yi Xue Za Zhi ; 100(3): 182-186, 2020 Jan 21.
Artigo em Chinês | MEDLINE | ID: mdl-32008283

RESUMO

Objective: To analyze morphological changes in central sulcus of the cerebral cortex in children with complete growth hormone deficiency (CGHD). Methods: Patients attending the Shandong Provincial Hospital who were diagnosed with CGHD or idiopathic short stature were recruited from January 2015 to January 2019. Thirty children with CGHD (18 males and 12 females, 5 to 14 years old) and 30 children with idiopathic short stature (22 males and 8 females, 5 to 14 years old) were included. Measurements of the central sulcus, including the average width, maximum depth, average depth, top length, bottom length and depth position-based profiles (DPP), were obtained using Brain VISA software. The significant differences between groups were statistically analyzed. Results: The average width of bilateral central sulci in children with CGHD (left: (2.26±0.41) mm; right: (2.19±0.34) mm) were significantly higher than those in children with idiopathic short stature (left: (2.10±0.27) mm; right: (2.02±0.18) mm) (P<0.05) ; The maximum depth of the left central sulcus ((19.67±1.29) mm) and the average depth of the right central sulcus ((14.18±1.41) mm) were significantly lower than those in children with idiopathic short stature (left maximum depth: (20.69±1.43) mm; right average depth: (14.92±1.21) mm) (P<0.05) . Children with CGHD had significantly lower DPP at the middle part of the left central sulcus (sites: 46-54) and the inferior part of the right central sulcus(sites: 91-98). Conclusion: There are significant morphological changes of the central sulcus in children with CGHD, which may represent the structural basis of their relatively slower development in motor, cognitive and linguistic functional performance.


Assuntos
Encéfalo/patologia , Córtex Cerebral/anatomia & histologia , Hormônio do Crescimento/deficiência , Imagem por Ressonância Magnética/métodos , Adolescente , Encéfalo/fisiopatologia , Mapeamento Encefálico , Criança , Pré-Escolar , Feminino , Humanos , Masculino
12.
J Anim Sci ; 98(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31922564

RESUMO

Lysine is the first limiting amino acid (AA) in typical swine diets. Our previous research showed that dietary lysine restriction compromised the growth performance of late-stage finishing pigs, which was associated with the changes in plasma concentrations of nutrient metabolites and hormone insulin-like growth factor 1 (IGF-1). This study was conducted to investigate how dietary lysine restriction affects the plasma concentrations of selected metabolites and three anabolic hormones in growing pigs. Twelve individually penned young barrows (Yorkshire × Landrace; 22.6 ± 2.04 kg) were randomly assigned to two dietary treatments (n = 6). Two corn and soybean meal based diets were formulated to contain 0.65% and 0.98% standardized ileal digestible lysine as a lysine-deficient (LDD) and a lysine-adequate (LAD) diets, respectively. During the 8-week feeding trial, pigs had ad libitum access to water and their respective diets, and the growth performance parameters including average daily gain (ADG), average daily feed intake (ADFI), and gain-to-feed ratio (G:F) were determined. At the end of the trial, jugular vein blood was collected for plasma preparation. The plasma concentrations of free AA and six metabolites were analyzed with the established chemical methods, and the hormone concentrations were analyzed with the commercial ELISA kits. Data were analyzed with Student's t-test. The ADG of LDD pigs was lower (P < 0.01) than that of LAD pigs, and so was the G:F (P < 0.05) since there was no difference in the ADFI between the two groups of pigs. In terms of free AA, the plasma concentrations of lysine, methionine, leucine, and tyrosine were lower (P < 0.05), while that of ß-alanine was higher (P < 0.01), in the LDD pigs. The total plasma protein concentration was lower (P < 0.02) in the LDD pigs, whereas no differences were observed for the other metabolites between the two groups. No differences were observed in the plasma concentrations of growth hormone (GF), insulin, and IGF-1 between the two groups as well. These results indicate that the lack of lysine as a protein building block must be the primary reason for a reduced body protein synthesis and, consequently, the compromised G:F ratio and ADG. The changes in the plasma concentrations of total protein and four AA suggest that the compromised growth performance might be associated with some cell signaling and metabolic pathways that may not involve the GH/IGF-1 axis.


Assuntos
Ração Animal/análise , Dieta/veterinária , Hormônio do Crescimento/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Lisina/administração & dosagem , Suínos/fisiologia , Aminoácidos/metabolismo , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Íleo/metabolismo , Masculino , Soja/metabolismo , Ganho de Peso , Zea mays/química
14.
Gen Comp Endocrinol ; 287: 113357, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31821794

RESUMO

Growth hormone is a hormone secreted from the pituitary and is involved in the regulation of most major physiological processes such as growth, development and metabolism. Therefore, an accurate and sensitive detection method is needed for the detection of tilapia serum Gh level. Phage display technology is widely used in the expression of antibody fragments, in which fragments of antibodies are expressed as a fusion with phage proteins and are displayed on the phage surface for easy screening. Time-resolved fluorescence immunoassay (TRFIA) is a microanalysis method developed nearly two decades ago and is one of the most sensitive analytical techniques. With the use of a special lanthanide, the detection background can be distinguished, which can greatly improve the sensitivity of detection. In this report, we cloned the VH and VL DNA fragments from the lymphocytes of rabbits immunized with recombinant Gh and assembled them with a linker to form a single-chain variable fragment (scFv) gene pool. Using phage display technology, we isolated scFv DNA fragments from the pool, which encode a protein that specifically binds to tilapia Gh. We then established Eu-DTTA-based TRFIA for measuring plasma Gh in tilapia. The sensitivity of double antibody sandwich Gh-TRFIA was 0.225 ng/ml, and the linear range of the standard curve was 0.225-250 ng/ml. The intra- and interassay coefficients of variation (CVs) were <9.1 and <4.5%, respectively. The cross-reactivities (CRs) of 1 µg/ml recombinant tilapia somatolactin (rtSl), prolactin (rtPrl) and thyroid-stimulating hormone beta subunit (rtTshb) were 0.042%, 0.472% and 0.036%, respectively. The sensitivity of direct competitive Gh-TRFIA was 0.208 ng/ml, and the linear range of the standard curve was 0.208-500 ng/ml. The intra- and interassay CVs were <4.8 and <7.1%, respectively. The CRs of 1 µg/ml rtSl, rtPrl and rtTshb were 0.041%, 0.079% and 0.073%, respectively. In conclusion, Gh-TRFIA is a safe (no concerns about radioactive isotopes), economical, and efficient detection method for the quantification of plasma Gh. Thus, the application of phage display technology for antibody screening and the use of TRFIA for tilapia Gh detection are conducive to research in the field of fish endocrinology.


Assuntos
Fluorimunoensaio/métodos , Hormônio do Crescimento/sangue , Hipófise/metabolismo , Animais , Peixes , Tilápia
15.
Nat Rev Endocrinol ; 16(3): 135-146, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31780780

RESUMO

The ability of growth hormone (GH) to induce adipose tissue lipolysis has been known for over five decades; however, the molecular mechanisms that mediate this effect and the ability of GH to inhibit insulin-stimulated glucose uptake have scarcely been documented. In this same time frame, our understanding of adipose tissue has evolved to reveal a complex structure with distinct types of adipocyte, depot-specific differences, a biologically significant extracellular matrix and important endocrine properties mediated by adipokines. All these aforementioned features, in turn, can influence lipolysis. In this Review, we provide a historical and current overview of the lipolytic effect of GH in humans, mice and cultured cells. More globally, we explain lipolysis in terms of GH-induced intracellular signalling and its effect on obesity, insulin resistance and lipotoxicity. In this regard, findings that define molecular mechanisms by which GH induces lipolysis are described. Finally, data are presented for the differential effect of GH on specific adipose tissue depots and on distinct classes of metabolically active adipocytes. Together, these cellular, animal and human studies reveal novel cellular phenotypes and molecular pathways regulating the metabolic effects of GH on adipose tissue.


Assuntos
Tecido Adiposo/metabolismo , Hormônio do Crescimento/metabolismo , Animais , Humanos , Mutação , Hormônios Tireóideos/metabolismo
16.
J Clin Endocrinol Metab ; 105(3)2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31650157

RESUMO

CONTEXT: The X-linked immunoglobulin superfamily, member 1 (IGSF1), gene is highly expressed in the hypothalamus and in pituitary cells of the POU1F1 lineage. Human loss-of-function mutations in IGSF1 cause central hypothyroidism, hypoprolactinemia, and macroorchidism. Additionally, most affected adults exhibit higher than average IGF-1 levels and anecdotal reports describe acromegaloid features in older subjects. However, somatotrope function has not yet been formally evaluated in this condition. OBJECTIVE: We aimed to evaluate the role of IGSF1 in human and murine somatotrope function. PATIENTS, DESIGN, AND SETTING: We evaluated 21 adult males harboring hemizygous IGSF1 loss-of-function mutations for features of GH excess, in an academic clinical setting. MAIN OUTCOME MEASURES: We compared biochemical and tissue markers of GH excess in patients and controls, including 24-hour GH profile studies in 7 patients. Parallel studies were undertaken in male Igsf1-deficient mice and wild-type littermates. RESULTS: IGSF1-deficient adult male patients demonstrated acromegaloid facial features with increased head circumference as well as increased finger soft-tissue thickness. Median serum IGF-1 concentrations were elevated, and 24-hour GH profile studies confirmed 2- to 3-fold increased median basal, pulsatile, and total GH secretion. Male Igsf1-deficient mice also demonstrated features of GH excess with increased lean mass, organ size, and skeletal dimensions and elevated mean circulating IGF-1 and pituitary GH levels. CONCLUSIONS: We demonstrate somatotrope neurosecretory hyperfunction in IGSF1-deficient humans and mice. These observations define a hitherto uncharacterized role for IGSF1 in somatotropes and indicate that patients with IGSF1 mutations should be evaluated for long-term consequences of increased GH exposure.


Assuntos
Imunoglobulinas/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Proteínas de Membrana/fisiologia , Neurossecreção/fisiologia , Somatotrofos/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Hormônio do Crescimento/biossíntese , Humanos , Imunoglobulinas/deficiência , Fator de Crescimento Insulin-Like I/análise , Peptídeos e Proteínas de Sinalização Intercelular/deficiência , Masculino , Proteínas de Membrana/deficiência , Camundongos , Pessoa de Meia-Idade
17.
Chemosphere ; 240: 124936, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31568941

RESUMO

Triphenyltin (TPT) is widely used and commonly found in a water environment, so its effects on aquatic systems are of great concern. This study aimed to reveal the effects of chronic parental exposure of TPT on thyroid disruption and growth inhibition in zebrafish. Adult zebrafish (F0 generation) were exposed to environmentally relevant concentrations (1, 10, and 100 ng/L) of TPT for 60 days, and the larvae (F1 generation) were tested without TPT treatment. Results demonstrated that parental exposure to TPT disrupts thyroid function in zebrafish offspring: serum thyroxine (T4) significantly decreased, while serum 3,5,3'-triiodothyronine (T3) increased, and several genes involved in the hypothalamic-pituitary-thyroid (HPT) axis were down-regulated. In addition, we observed developmental abnormalities in the larvae, demonstrated by a significantly altered hatching rate, malformation rate, body length, heart rate, and survival rate, as well as down-regulation of genes involved in the growth hormone/insulin-like growth factor (GH/IGF) axis. Therefore, parental exposure to TPT induces toxicity in fish offspring through perturbation of the HPT and GH/IGF axes.


Assuntos
Larva/crescimento & desenvolvimento , Compostos Orgânicos de Estanho/toxicidade , Praguicidas/toxicidade , Glândula Tireoide/patologia , Poluentes Químicos da Água/toxicidade , Animais , Feminino , Hormônio do Crescimento/genética , Hormônio do Crescimento/metabolismo , Larva/efeitos dos fármacos , Masculino , Exposição Materna/efeitos adversos , Exposição Paterna/efeitos adversos , Somatomedinas/genética , Somatomedinas/metabolismo , Glândula Tireoide/efeitos dos fármacos , Tiroxina/sangue , Tri-Iodotironina/sangue , Peixe-Zebra/embriologia
18.
Heart Fail Clin ; 16(1): 11-21, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31735309

RESUMO

"Chronic heart failure (CHF) is a complex syndrome characterized by symptoms and signs supported by different forms of cardiac impairment. The link between multiple hormonal and metabolic derangements and the development of CHF and the beneficial effects seen with hormonal replacement therapy suggest that a reduction of anabolic pathways might contribute to the onset of CHF. Therefore, an imbalance between anabolic and catabolic forces could be responsible for the development of CHF. There are sufficient evidence to support the screening in patients with CHF of hormonal deficiencies and their correction with replacement therapy."


Assuntos
Hormônio do Crescimento/sangue , Insuficiência Cardíaca/metabolismo , Resistência à Insulina , Doenças Metabólicas/etiologia , Testosterona/sangue , Hormônios Tireóideos/sangue , Biomarcadores/sangue , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Terapia de Reposição Hormonal/métodos , Humanos , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/metabolismo
19.
J Sci Food Agric ; 100(2): 755-763, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31605375

RESUMO

BACKGROUND: ß-Hydroxy-ß-methylbutyrate (HMB) is the metabolite of leucine that plays an important role in muscle protein metabolism. The objective of the present study was to determine the effects of in ovo feeding (IOF) of HMB at 7 days of incubation (DOI) via air cell or 18 DOI via amnion on hatchability, muscle growth and performance in prenatal and posthatch broilers. RESULTS: IOF of HMB via air cell at 7 DOI increased hatchability by 4.34% compared with the control (89.67% versus 85.33%). Birds in IOF groups exhibited higher body weight, average daily body weight gain and pectoral muscle percentage. Furthermore, IOF of HMB significantly increased the level of plasma growth hormone, insulin and insulin-like growth factor-1. Chicks hatched from IOF treatment had larger diameters of muscle fiber and higher mitotic activity of satellite cells at early posthatch age. IOF of HMB activated satellite cells by upregulation of mRNA expression of myogenic transcription factors, myogenic differentiation one (MyoD) and myogenin. Chicks hatched from air cell injection group had higher pectoral muscle percentage at 5 d posthatch and greater satellite cell mitotic activity at 7 d posthatch than counterparts from amnion injection group. CONCLUSIONS: IOF of HMB via amnion at 18 DOI or especially via air cell at 7 DOI could be used as an effective approach to enhance hatchability, productive performance and breast muscle yield in broilers. © 2019 Society of Chemical Industry.


Assuntos
Galinhas/fisiologia , Músculos Peitorais/crescimento & desenvolvimento , Valeratos/metabolismo , Ração Animal/análise , Animais , Galinhas/sangue , Galinhas/genética , Galinhas/crescimento & desenvolvimento , Suplementos Nutricionais/análise , Comportamento Alimentar , Feminino , Hormônio do Crescimento/sangue , Insulina/sangue , Masculino , Mitose , Proteína MyoD/genética , Proteína MyoD/metabolismo , Mioblastos/citologia , Mioblastos/metabolismo , Miogenina/genética , Miogenina/metabolismo , Músculos Peitorais/metabolismo
20.
Artigo em Inglês | MEDLINE | ID: mdl-31874288

RESUMO

Although zinc is an essential element for organisms, excess zinc exposure is harmful. We assessed the possible negative influence of zinc (Zn) on the freshwater fish Danio rerio during its early life stage by using Organization for Economic Cooperation and Development test guideline no. 210. Lethality of Zn after hatching occurred in a concentration dependent manner. The LC50 and lowest observed effect concentration of mortality values in the present toxicity assay were 2.31 mg/L (95% confidence limit: 1.81-3.05) and 1.5 mg/L, respectively. These values were close to the reported concentration recorded in aquatic environments. Growth inhibition was observed at 15 and 30 days post-hatching with Zn exposure of 1.5 mg/L. In general, the growth hormone (Gh)/insulin-like growth factor-I (Igf-1) axis is important for growth in fishes, and Zn exposure induced a significant reduction of igf-1 expression at the concentration that caused growth inhibition. These findings suggest that the observed growth inhibition was induced by the suppression of igf-1 expression. In addition, these results suggest that by examining gene expression on the Gh/Igf-1 axis, it may be possible to predict growth suppression by chemical exposure.


Assuntos
Cloretos/toxicidade , Larva/crescimento & desenvolvimento , Poluentes Químicos da Água/toxicidade , Peixe-Zebra , Compostos de Zinco/toxicidade , Zinco/toxicidade , Zigoto , Animais , Desenvolvimento Embrionário , Hormônio do Crescimento/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Larva/metabolismo , Dose Letal Mediana , Peixe-Zebra/crescimento & desenvolvimento , Peixe-Zebra/metabolismo , Zigoto/crescimento & desenvolvimento , Zigoto/metabolismo
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