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1.
Ecotoxicol Environ Saf ; 201: 110820, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32531574

RESUMO

Growth hormone (GH)/insulin-like growth factor (IGF) axis plays a critical role in fetal development. However, the effect of arsenite exposure on the GH/IGF axis and its toxic mechanism are still unclear. Zebrafish embryos were exposed to a range of NaAsO2 concentrations (0.0-10.0 mM) between 4 and 120 h post-fertilization (hpf). Development indexes of survival, malformation, hatching rate, heart rate, body length and locomotor behavior were measured. Hormone levels, GH/IGF axis-related genes, and nerve-related genes were also tested. The results showed that survival rate, hatching rate, heart rate, body length and locomotor behavior all decreased, while deformity increased. At 120 hpf, the survival rate of zebrafish in 1.5 mM NaAsO2 group was about 70%, the deformity rate exceeded 20%, and the body length shortened to 3.35 mm, the movement distance of zebrafish decreased approximately 63.6% under light condition and about 52.4% under dark condition. The level of GH increased and those of IGF did not change significantly, while the expression of GH/IGF axis related genes (ghra, ghrb, igf2r, igfbp3, igfbp2a, igfbp5b) and nerve related genes (dlx2, shha, ngn1, elavl3, gfap) decreased. In 1.5 mM NaAsO2 group, the decrease of igfbp3 and igfbp5b was almost obvious, about 78.2% and 72.2%. The expression of nerve genes in 1.5 mM NaAsO2 group all have declined by more than 50%. These findings suggested that arsenite exerted disruptive effects on the endocrine system by interfering with the GH/IGF axis, leading to zebrafish embryonic developmental toxicity.


Assuntos
Arsenitos/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Hormônio do Crescimento/metabolismo , Somatomedinas/metabolismo , Peixe-Zebra , Animais , Embrião não Mamífero/metabolismo , Desenvolvimento Embrionário/genética , Sistema Endócrino/efeitos dos fármacos , Sistema Endócrino/embriologia , Sistema Endócrino/metabolismo , Hormônio do Crescimento/genética , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Transdução de Sinais , Somatomedinas/genética , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
2.
World Neurosurg ; 139: 310-313, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32339726

RESUMO

BACKGROUND: Pituitary blastoma is a malignant neoplasm of the pituitary gland that was recognized by the World Health Organization in 2017. It is commonly diagnosed in children before 24 months of age. Here, we report the first case of a young adult patient who was diagnosed with pituitary blastoma with increased levels of growth hormone instead of adrenocorticotropic hormone and provide a review of the literature. CASE DESCRIPTION: A 19-year-old woman presented to our hospital with visual disturbance. She had a medical history of Wilms' tumor and multinodular goiter. The brain imaging showed a 3.2 × 2.5 × 1.8-cm solid sellar and suprasellar cystic mass that upwardly displaced the optic chiasm. She had an elevated level of growth hormone but a normal level of adrenocorticotropic hormone, cortisol, and prolactin. The mass was subtotally removed through the left pterional craniotomy. The pathologic examination suggested a pituitary blastoma. Thereafter, the patient was treated with chemotherapy and radiotherapy. At 4-year follow-up postsurgery, her overall well-being is good. CONCLUSIONS: Although in this case the patient was a young adult, pituitary blastoma should be taken into consideration when children have an enhanced sellar and suprasellar mass with peripherally located cysts.


Assuntos
Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias da Glândula Tireoide/patologia , Feminino , Bócio Nodular , Hormônio do Crescimento/metabolismo , Humanos , Neoplasias Renais , Neoplasias Embrionárias de Células Germinativas/metabolismo , Neoplasias Embrionárias de Células Germinativas/cirurgia , Segunda Neoplasia Primária/patologia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/cirurgia , Tumor de Wilms , Adulto Jovem
3.
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
4.
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
5.
Endocrinology ; 161(4)2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32100023

RESUMO

The gut microbiome has been implicated in host metabolism, endocrinology, and pathophysiology. Furthermore, several studies have shown that gut bacteria impact host growth, partially mediated through the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis. Yet, no study to date has examined the specific role of GH on the gut microbiome. Our study thus characterized the adult gut microbial profile and intestinal phenotype in GH gene-disrupted (GH-/-) mice (a model of GH deficiency) and bovine GH transgenic (bGH) mice (a model of chronic, excess GH action) at 6 months of age. Both the GH-/- and bGH mice had altered microbial signatures, in opposing directions at the phylum and genus levels. For example, GH-/- mice had significantly reduced abundance in the Proteobacteria, Campylobacterota, and Actinobacteria phyla, whereas bGH mice exhibited a trending increase in those phyla compared with respective controls. Analysis of maturity of the microbial community demonstrated that lack of GH results in a significantly more immature microbiome while excess GH increases microbial maturity. Several common bacterial genera were shared, although in opposing directions, between the 2 mouse lines (e.g., decreased in GH-/- mice and increased in bGH mice), suggesting an association with GH. Similarly, metabolic pathways like acetate, butyrate, heme B, and folate biosynthesis were predicted to be impacted by GH. This study is the first to characterize the gut microbiome in mouse lines with altered GH action and indicates that GH may play a role in the growth of certain microbiota thus impacting microbial maturation and metabolic function.


Assuntos
Nanismo Hipofisário/microbiologia , Microbioma Gastrointestinal/fisiologia , Hormônio do Crescimento/metabolismo , Animais , Nanismo Hipofisário/genética , Nanismo Hipofisário/metabolismo , Hormônio do Crescimento/genética , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos
6.
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
7.
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
8.
Gen Comp Endocrinol ; 288: 113377, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31881203

RESUMO

The synergy between the genetic potential and the nutrient intake determines the growth performance of meat-type chicken and nutrigenomics approach helps us understand the response of candidate genes of growth in chicken to dietary manipulations. The current study aimed to assess the growth performance and expression of hepatic growth related genes in the naked neck broiler chicken in response to different dietary energy and protein levels with a hypothesis that high plane of nutrition enhances both of these positively. The results revealed that birds have shown significantly better growth performance under high protein (HP) and high energy (HE) dietary regime. The expression profiles of the genes studied revealed upregulation of IGF-1, IGF-2, and GH under dietary HP and HE regime relative to other protein and energy levels with greater upregulation at 3rd week than the 1st and 5th week of age of birds. The IGFR and GHR mRNA expression was significantly higher under HP and HE dietary regimen with an increasing and decreasing trend from 1st to 5th week of age, respectively. A consistent and significant downregulation of IGFBP-2 was observed under HP and HE regime throughout the feeding trial. The myostatin expression was higher at 3rd week of age followed by 1st week expression. The HP and HE as well as LP (Low protein) and HE diet resulted in significant upregulation of myostatin gene expression in liver. In support to the set hypothesis of this study the high protein and high energy diet resulted in better growth performance of broiler chickens with corresponding upregulation of IGF-1, IGF-2, IGFR, GH, GHR, and Myostatin gene expression and downregulation of IGFBP-2 in liver.


Assuntos
Galinhas/crescimento & desenvolvimento , Galinhas/genética , Dieta , Proteínas na Dieta/administração & dosagem , Metabolismo Energético/efeitos dos fármacos , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal/genética , Animais , Galinhas/metabolismo , Proteínas na Dieta/farmacologia , Ingestão de Energia/efeitos dos fármacos , Metabolismo Energético/genética , Feminino , Expressão Gênica/efeitos dos fármacos , Hormônio do Crescimento/genética , Hormônio do Crescimento/metabolismo , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/metabolismo , Masculino , Distribuição Aleatória , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo
9.
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
10.
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
11.
Endocrinology ; 161(2)2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31875887

RESUMO

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway has cell-specific functions. Suppressors of cytokine signaling (SOCS) proteins are negative-feedback regulators of JAK-STAT signaling. STAT5 plays a significant role in adipocyte development and function, and bromodomain and extraterminal (BET) proteins may be involved in STAT5 transcriptional activity. We treated 3T3-L1 adipocytes with the BET inhibitor JQ1 and observed that growth hormone (GH)-induced expression of 2 STAT5 target genes from the SOCS family, Socs3 and Cish, were inversely regulated (increased and decreased, respectively) by BET inhibition. Chromatin immunoprecipitation analyses revealed that changes in STAT5 binding did not correlate with gene expression changes. GH promoted the recruitment of the BET protein BRD2 to the Cish, but not Socs3, promoter. JQ1 treatment ablated this effect as well as the GH-induced binding of ribonucleic acid polymerase II (RNA Pol II) to the Cish transcription start site. BRD2 knockdown also suppressed GH induction of Cish, further supporting the role of BRD2 in Cish transcriptional activation. In contrast, JQ1 increased the binding of activated Pol II to the Socs3 coding region, suggesting enhanced messenger RNA (mRNA) elongation. Our finding that JQ1 transiently reduced the interaction between the positive transcription elongation factor (P-TEFb) and its inhibitor hexamethylene bis-acetamide inducible 1 (HEXIM1) is consistent with a previously described off-target effect of JQ1, whereby P-TEFb becomes more available to be recruited by genes that do not depend on BET proteins for activating transcription. These results demonstrate substantially different transcriptional regulation of Socs3 and Cish and suggest distinct roles in adipocytes for these 2 closely related proteins.


Assuntos
Adipócitos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio do Crescimento/metabolismo , Proteínas Nucleares/antagonistas & inibidores , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Animais , Azepinas , Camundongos , Fator B de Elongação Transcricional Positiva/metabolismo , Proteínas de Ligação a RNA/metabolismo , Fatores de Transcrição/metabolismo , Triazóis
12.
Aquat Toxicol ; 217: 105336, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31733503

RESUMO

It is widely recognized that endocrine disrupting chemicals (EDCs) released into the environment through anthropogenic activities can have short-term impacts on physiological and behavioral processes and/or sustained or delayed long-term developmental effects on aquatic organisms. While numerous studies have characterized the effects of EDCs on temperate fishes, less is known on the effects of EDCs on the growth and reproductive physiology of tropical species. To determine the long-term effects of early-life exposure to common estrogenic chemicals, we exposed Mozambique tilapia (Oreochromis mossambicus) yolk-sac fry to 17ß-estradiol (E2) and nonylphenol (NP) and subsequently characterized the expression of genes involved in growth and reproduction in adults. Fry were exposed to waterborne E2 (0.1 and 1 µg/L) and NP (10 and 100 µg/L) for 21 days. After the exposure period, juveniles were reared for an additional 112 days until males were sampled. Gonadosomatic index was elevated in fish exposed to E2 (0.1 µg/L) while hepatosomatic index was decreased by exposure to NP (100 µg/L). Exposure to E2 (0.1 µg/L) induced hepatic growth hormone receptor (ghr) mRNA expression. The high concentration of E2 (1 µg/L), and both concentrations of NP, increased hepatic insulin-like growth-factor 1 (igf1) expression; E2 and NP did not affect hepatic igf2 and pituitary growth hormone (gh) levels. Both E2 (1 µg/L) and NP (10 µg/L) induced hepatic igf binding protein 1b (igfbp1b) levels while only NP (100 µg/L) induced hepatic igfbp2b levels. By contrast, hepatic igfbp6b was reduced in fish exposed to E2 (1 µg/L). There were no effects of E2 or NP on hepatic igfbp4 and igfbp5a expression. Although the expression of three vitellogenin transcripts was not affected, E2 and NP stimulated hepatic estrogen receptor (erα and erß) mRNA expression. We conclude that tilapia exposed to E2 and NP as yolk-sac fry exhibit subsequent changes in the endocrine systems that control growth and reproduction during later life stages.


Assuntos
Estradiol/toxicidade , Hormônio do Crescimento/metabolismo , Fenóis/toxicidade , Receptores Estrogênicos/metabolismo , Somatomedinas/metabolismo , Tilápia/crescimento & desenvolvimento , Poluentes Químicos da Água/toxicidade , Animais , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Fígado/efeitos dos fármacos , Masculino , Reprodução/efeitos dos fármacos , Tilápia/metabolismo , Vitelogeninas/metabolismo
13.
Int J Mol Sci ; 20(19)2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31623386

RESUMO

This study aimed to examine the effect of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and growth hormone (GH) on Aquaporin 5 (AQP5) expression in granulosa (Gc) and theca cells (Tc) from medium (MF) and large (LF) ovarian follicles of pigs. The results showed that GH significantly decreased the expression of AQP5 in Gc from MF in relation to the control. In the Gc of large follicles, PRL stimulated the expression of AQP5. However, the increased expression of AQP5 in the Tc of LF was indicated by GH and PRL in relation to the control. A significantly higher expression of the AQP5 protein in the Gc from MF and LF was indicated by FSH and PRL. In co-cultures, an increased expression of AQP5 was observed in the Gc from LF incubated with LH, PRL, and GH. A significantly increased expression of AQP5 was also observed in co-cultures of Tc from all type of follicles incubated with LH, whereas PRL stimulated the expression of AQP5 in Tc from MF. Moreover, AQP5 protein expression increased in the co-culture isolated from MF and LF after treatment with FSH, LH, PRL, and GH. AQP5 immunoreactivity was observed in the cytoplasm, mainly in the perinuclear region and endosomes, as well as in the cell membranes of Gc and Tc from the LF and MF.


Assuntos
Aquaporina 5/genética , Regulação da Expressão Gênica de Plantas , Folículo Ovariano/metabolismo , Hormônios Hipofisários/metabolismo , Animais , Biomarcadores , Técnicas de Cocultura , Feminino , Hormônio Foliculoestimulante/metabolismo , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Hormônio do Crescimento/metabolismo , Hormônio Luteinizante/metabolismo , Folículo Ovariano/citologia , Folículo Ovariano/efeitos dos fármacos , Hormônios Hipofisários/farmacologia , Prolactina/metabolismo , Suínos , Células Tecais/efeitos dos fármacos , Células Tecais/metabolismo
14.
J Physiol Pharmacol ; 70(4)2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31642814

RESUMO

Early weaning of ewe lambs strongly stimulates the hypothalamic-pituitary-adrenal axis and is associated with suppressed growth rate despite the increased food intake. At the same time, plasma leptin concentration increases only slightly or undetectably. To better understand this atypical interdependence among somatic stress, leptin, and lamb growth rate, we analyzed impact of leptin and/or adrenocorticotropic hormone (ACTH) on growth hormone (GH) secretion as well as the effect of ACTH on mRNA expression of two splice variants of leptin receptor (LEPRa, LEPRb) in pituitary cells isolated from early weaned ewe lambs. The GH secretion under the influence of leptin and/or ACTH depended on the timing of exposure and hormone concentration. After 6 - 30 h, GH secretion increased under 10-11 - 10-8 M leptin (P ≤ 0.05). However, after 24 - 30 h, GH secretion significantly increased only in cells exposed to both leptin and ACTH compared to culture with leptin only. Simultaneously, there was a significant (P ≤ 0.05) decrease in leptin receptor mRNA expression under the influence of ACTH at 10-8 - 10-6 M after 12 - 30 and 24 - 30 h for LEPRa and LEPRb, respectively. ACTH-related downregulation of LEPR mRNA was associated with a significant (P ≤ 0.05) reduction in leptin-stimulated GH secretion, also after 24 - 30 hours. Thus, the timing of ACTH exposure, followed by decreased leptin receptor mRNA, converged with the timing of decreased GH secretion under the influence of leptin with ACTH. The ACTH-induced downregulation of LEPR mRNA therefore may underlie the decrease in GH. These results show a direct role for leptin, ACTH, and leptin receptor expression in modulation of pituitary GH secretion in early weaned ewe lambs. During the early weaning-induced stress response, the ACTH-mediated decrease in sensitivity of pituitary cells to leptin may abolish a stimulatory effect of leptin on GH secretion and explain in part, the reduction in lamb growth rate.


Assuntos
Hormônio Adrenocorticotrópico/farmacologia , Hormônio do Crescimento/metabolismo , Leptina/farmacologia , Receptores para Leptina/genética , Animais , Feminino , Hipófise/citologia , Hipófise/metabolismo , RNA Mensageiro/metabolismo , Ovinos , Desmame
15.
Int J Mol Sci ; 20(21)2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31652811

RESUMO

Growth hormone (GH) is best known for its prominent role in promoting prepubertal growth and in regulating body composition and metabolism during adulthood. In recent years, the possible role of GH in the modulation of mesenchymal stem cell (MSC) commitment has gained interest. MSCs, characterized by active self-renewal and differentiation potential, express GH receptors. In MSCs derived from different adult tissues, GH induces an inhibition of adipogenic differentiation and favors MSC differentiation towards osteogenesis. This activity of GH indicates that regulation of body composition by GH has already started in the tissue progenitor cells. These findings have fostered research on possible uses of MSCs treated with GH in those pathologies, where a lack of or delays in bone repair occur. After an overview of GH activities, this review will focus on the research that has characterized GH's effects on MSCs and on preliminary studies on the possible application of GH in bone regenerative medicine.


Assuntos
Regeneração Óssea , Hormônio do Crescimento/metabolismo , Células-Tronco Mesenquimais/metabolismo , Animais , Diferenciação Celular , Humanos , Células-Tronco Mesenquimais/citologia , Medicina Regenerativa/métodos
16.
Endocr J ; 66(11): 943-952, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31564683

RESUMO

Malnutrition occurs when nutrient intake is too low for any reason and occurs regardless of gender or age. Therefore, besides loss of eating or digestive functionality due to illness, malnutrition can occur when a healthy individual undergoes an extreme diet and biases their nutrition, or when athletes exerts more energy than they can replenish through food. It has recently been reported that in Japan, the mortality rate of leaner individuals is equal to or higher than that of obese people. It is important to understand what homeostatic maintenance mechanism is behind this when the body is under hypotrophic conditions. Such mechanisms are generally endocranially controlled. We address this fundamental concern in this paper by focusing on peptide hormones. We introduce a mechanism for survival in a malnourished state via the regulation of food intake and temperature. Additionally, we will discuss the latest findings and future prospects for research on changes in the endocrine environment associated with malnutrition associated with exercise. We also review changes in next-generation endocrine environments when caused by malnutrition brought on by dieting.


Assuntos
Metabolismo Energético/fisiologia , Comportamento Alimentar/fisiologia , Desnutrição/metabolismo , Hormônios Peptídicos/metabolismo , Temperatura Corporal , Dieta Redutora , Ingestão de Energia , Epigênese Genética , Exercício Físico/fisiologia , Feminino , Grelina/metabolismo , Hormônio do Crescimento/metabolismo , Humanos , Insulina/metabolismo , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Leptina/metabolismo , Neuropeptídeo Y/metabolismo , Hormônios Peptídicos/genética , Peptídeo YY/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Esportes , Termogênese
17.
PLoS One ; 14(9): e0222340, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31509580

RESUMO

Growth hormone (GH) is an important hormone released by the pituitary gland that plays a key role in the growth and development of organisms. In our study, TargetScan analysis and the dual luciferase reporter assays were used to predict and screen for miRNAs that might act on the rat Gh1 gene, and we identified miR-543-5p. Then, the GH3 cell line and the primary rat pituitary cells were transfected with miRNA mimic, inhibitor, and siRNA. We detected the Gh1 gene expression and the GH secretion by real-time PCR and ELISAs, respectively, to verify the regulatory effect of miR-543-5p on GH secretion. The results showed that miR-543-5p can inhibit Gh1 mRNA expression and reduce GH secretion. MiR-543-5p inhibitor upregulated Gh1 mRNA expression and increased GH secretion compared with the negative control. In summary, miR-543-5p downregulates Gh1 expression, resulting in a decrease in GH synthesis and secretion, which demonstrates the important role of miRNAs in regulating GH and animal growth and development.


Assuntos
Hormônio do Crescimento/genética , MicroRNAs/genética , Hormônios Adeno-Hipofisários/genética , Regiões 3' não Traduzidas/genética , Animais , Linhagem Celular , Expressão Gênica , Regulação da Expressão Gênica/genética , Hormônio do Crescimento/metabolismo , Masculino , Hipófise/metabolismo , Adeno-Hipófise/metabolismo , Hormônios Adeno-Hipofisários/metabolismo , Cultura Primária de Células , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Transfecção
18.
Growth Horm IGF Res ; 48-49: 36-44, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31494533

RESUMO

OBJECTIVE: To investigate the anti-inflammatory property of ghrelin treatment on the Growth Hormone (GH)/Insulin-like Growth Factor-I (IGF-1) axis in Wistar rats that have undergone endotoxemia. DESIGN: In this randomized animal study, lipopolysaccharide (LPS) (5 mg/kg; intraperitoneal) was administered to induce endotoxemia, and ghrelin (15 nmol/kg; endovenous) was injected simultaneously. Blood and liver samples were collected 2 h, 6 h and 12 h after LPS administration for analysis. MEASUREMENTS: Tumor necrosis factor alpha (TNF-α), interleukin (IL)-1, beta (IL-1ß), and IL-6 from both blood and liver were determined by ELISA assay. Serum nitrate was determined by chemiluminescense. Growth hormone receptor (GHR) and growth hormone secretagogue receptor 1a (GHSR-1a) were determined by western blotting. GHR mRNA and IGF-1 mRNA were determined by RT-PCR. RESULTS: LPS administration induced a decrease in IGF-1 and GH serum levels, characterizing GH/IGF-1 axis disruption. Ghrelin treatment attenuated the decrease of serum levels of IGF-1 as well as the increase of TNF-α, IL-1ß, IL-6 and nitrate induced by LPS. The increase of induced GHSR-1a protein expression seen in the LPS group after 2 h remained until 6 h after ghrelin treatment. However, attenuation of the circulating IGF-1 decrease by ghrelin treatment was not accompanied by changes in GHR protein expression nor GHR and IGF-1 gene expression. CONCLUSION: Ghrelin was able to attenuate changes in the GH/IGF-1 axis observed during systemic inflammation, which may be due to the modulation of pro-inflammatory mediators release.


Assuntos
Endotoxemia/metabolismo , Grelina/farmacologia , Hormônio do Crescimento/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Receptores da Somatotropina/metabolismo , Animais , Citocinas/metabolismo , Endotoxemia/tratamento farmacológico , Endotoxemia/patologia , Lipopolissacarídeos/farmacologia , Masculino , Óxido Nítrico/metabolismo , Ratos , Ratos Wistar
19.
J Dairy Sci ; 102(11): 10340-10359, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31495618

RESUMO

We have shown in 2 independent studies that cows who received recombinant bovine interleukin-8 (rbIL-8) administered intrauterinely shortly after parturition have a significant and long-lasting increase in milk yield. In the present study, we hypothesized that the increased milk production associated with rbIL-8 treatment is a consequence of increased postpartum dry matter intake (DMI) and orchestrated homeorhetic changes that prioritize milk production. Cows were enrolled into 1 of 3 treatment groups: those assigned to the control group (CTR; n = 70) received an intrauterine (IU) administration of 500 mL of Dulbecco's phosphate-buffered saline (DPBS) solution and 1 mL of DPBS solution intravenously (IV; jugular vein), those assigned to the rbIL-8 IV group (rbIL8-IV, n = 70) received an IV injection of 167 µg of rbIL-8 and 500 mL of DPBS solution IU, and cows assigned to the rbIL-8 IU group (rbIL8-IU, n = 70) received an IU administration with 1,195 µg of rbIL-8 diluted in 499.5 mL of DPBS solution and 1 mL of DPBS solution IV. Animals were housed in a tiestall from calving to 30 d in milk (DIM) to measure DMI. Blood samples were collected daily from calving to 7 DIM and weekly until 28 DIM. Insulin resistance was evaluated using an intravenous glucose tolerance test and intravenous insulin challenge test (IVICT) in a subgroup of cows (n = 20/treatment) at 10 and 11 DIM, respectively. Additionally, liver biopsy samples were taken at 14 DIM from the same subgroup of cows to measure triglyceride levels and cell proliferation and apoptosis. Cows treated with rbIL8-IU produced more milk (CTR = 36.9 ± 1.5; rbIL8-IU = 38.5 ± 1.5; rbIL8-IV = 36.6 ± 1.5 kg/d), energy-corrected milk (CTR = 42.9 ± 0.9; rbIL8-IU = 46.1 ± 0.8; rbIL8-IV = 43.7 ± 0.9 kg/d), and fat-corrected milk (CTR = 44.3 ± 0.9; rbIL8-IU = 47.8 ± 0.9; rbIL8-IV = 45.2 ± 0.9 kg/d) yields when compared with CTR cows, and no differences were observed between rbIL8-IV and CTR cows. The administration of rbIL8-IU significantly increased DMI compared with CTR (CTR = 18.8 ± 0.3; rbIL8-IU = 19.9 ± 0.3; rbIL8-IV = 19.3 ± 0.3 kg/d). Recombinant bIL-8 treatment did not affect glucose, insulin, or fatty acids (i.e., IVICT only) concentrations or their area under the curve in response to an intravenous glucose tolerance test and IVICT when compared with CTR. Moreover, rbIL-8 treatment administered IU or IV increased liver triglyceride levels. Additionally, cows treated with rbIL8-IU tended to have lower odds of developing hyperketonemia (odds ratio = 0.46, 95% confidence interval: 0.19 to 1.10), lower odds of clinical ketosis and displaced abomasum combined (odds ratio = 0.17, 95% confidence interval: 0.03 to 0.89), and lower odds of diseases combined (odds ratio = 0.43, 95% confidence interval: 0.21 to 0.86) when compared with CTR. We conclude that the administration of rbIL8-IU increases DMI, milk production, fat-corrected milk, and energy-corrected milk while improving overall health during the postpartum period. This study supports the use of rbIL-8 administered IU shortly after calving to improve health and production responses in lactating cows.


Assuntos
Bovinos/fisiologia , Ingestão de Alimentos/efeitos dos fármacos , Resistência à Insulina , Interleucina-8/administração & dosagem , Lactação/efeitos dos fármacos , Ácido 3-Hidroxibutírico/sangue , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dieta/veterinária , Ácidos Graxos/metabolismo , Feminino , Glucose/metabolismo , Hormônio do Crescimento/efeitos dos fármacos , Hormônio do Crescimento/metabolismo , Insulina/sangue , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/metabolismo , Interleucina-8/metabolismo , Interleucina-8/farmacologia , Cetose/veterinária , Lactação/fisiologia , Fígado/citologia , Fígado/efeitos dos fármacos , Leite/metabolismo , Parto , Período Pós-Parto/sangue , Gravidez , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia
20.
PLoS One ; 14(8): e0221083, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31415653

RESUMO

Providing a broiler chicken embryo with a lighting schedule during incubation may stimulate leg bone development. Bone development may be stimulated through melatonin, a hormone released in darkness that stimulates bone development, or increased activity in embryos exposed to a light-dark rhythm. Aim was to investigate lighting conditions during incubation and leg bone development in broiler embryos, and to reveal the involved mechanisms. Embryos were incubated under continuous cool white 500 lux LED light (24L), continuous darkness (24D), or 16h of light, followed by 8h of darkness (16L:8D) from the start of incubation until hatching. Embryonic bone development largely takes place through cartilage formation (of which collagen is an important component) and ossification. Expression of genes involved in cartilage formation (col1α2, col2α1, and col10α1) and ossification (spp1, sparc, bglap, and alpl) in the tibia on embryonic day (ED)13, ED17, and at hatching were measured through qPCR. Femur and tibia dimensions were determined at hatch. Plasma growth hormone and corticosterone and pineal melatonin concentrations were determined every 4h between ED18.75 and ED19.5. Embryonic heart rate was measured twice daily from ED12 till ED19 as a reflection of activity. No difference between lighting treatments on gene expression was found. 24D resulted in higher femur length and higher femur and tibia weight, width, and depth at hatch than 16L:8D. 24D furthermore resulted in higher femur length and width and tibia depth than 24L. Embryonic heart rate was higher for 24D and 16L:8D in both its light and dark period than for 24L, suggesting that 24L embryos may have been less active. Melatonin and growth hormone showed different release patterns between treatments, but the biological significance was hard to interpret. To conclude, 24D resulted in larger leg bones at hatch than light during incubation, but the underlying pathways were not clear from present data.


Assuntos
Desenvolvimento Ósseo , Escuridão , Ossos da Perna/embriologia , Iluminação , Animais , Embrião de Galinha , Galinhas , Corticosterona/metabolismo , Hormônio do Crescimento/metabolismo , Melatonina/metabolismo
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