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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.
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
3.
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
4.
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
5.
BMC Genomics ; 20(1): 1024, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31881844

RESUMO

BACKGROUND: Transcriptomic responses to immune stimulation were investigated in coho salmon (Oncorhynchus kisutch) with distinct growth phenotypes. Wild-type fish were contrasted to strains with accelerated growth arising either from selective breeding (i.e. domestication) or genetic modification. Such distinct routes to accelerated growth may have unique implications for relationships and/or trade-offs between growth and immune function. RESULTS: RNA-Seq was performed on liver and head kidney in four 'growth response groups' injected with polyinosinic-polycytidylic acid (Poly I:C; viral mimic), peptidoglycan (PGN; bacterial mimic) or PBS (control). These groups were: 1) 'W': wild-type, 2) 'TF': growth hormone (GH) transgenic salmon with ~ 3-fold higher growth-rate than W, 3) 'TR': GH transgenic fish ration restricted to possess a growth-rate equal to W, and 4) 'D': domesticated non-transgenic fish showing growth-rate intermediate to W and TF. D and TF showed a higher similarity in transcriptomic response compared to W and TR. Several immune genes showed constitutive expression differences among growth response groups, including perforin 1 and C-C motif chemokine 19-like. Among the affected immune pathways, most were up-regulated by Poly I:C and PGN. In response to PGN, the c-type lectin receptor signalling pathway responded uniquely in TF and TR. In response to stimulation with both immune mimics, TR responded more strongly than other groups. Further, group-specific pathway responses to PGN stimulation included NOD-like receptor signalling in W and platelet activation in TR. TF consistently showed the most attenuated immune response relative to W, and more DEGs were apparent in TR than TF and D relative to W, suggesting that a non-satiating ration coupled with elevated circulating GH levels may cause TR to possess enhanced immune capabilities. Alternatively, TF and D salmon are prevented from acquiring the same level of immune response as TR due to direction of energy to high overall somatic growth. Further study of the effects of ration restriction in growth-modified fishes is warranted. CONCLUSIONS: These findings improve our understanding of the pleiotropic effects of growth modification on the immunological responses of fish, revealing unique immune pathway responses depending on the mechanism of growth acceleration and nutritional availability.


Assuntos
Hormônio do Crescimento/genética , Imunomodulação/genética , Oncorhynchus kisutch/genética , Oncorhynchus kisutch/imunologia , Transcriptoma , Animais , Animais Geneticamente Modificados , Cruzamento , Biologia Computacional/métodos , Domesticação , Perfilação da Expressão Gênica , Oncorhynchus kisutch/crescimento & desenvolvimento , Oncorhynchus kisutch/metabolismo , Especificidade de Órgãos
6.
PLoS One ; 14(10): e0223094, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31622367

RESUMO

Cranial cruciate ligament disease (CCLD) is a complex trait. Ten measurements were made on orthogonal distal pelvic limb radiographs of 161 pure and mixed breed dogs with, and 55 without, cranial cruciate partial or complete ligament rupture. Dogs with CCLD had significantly smaller infrapatellar fat pad width, higher average tibial plateau angle, and were heavier than control dogs. The first PC weightings captured the overall size of the dog's stifle and PC2 weightings reflected an increasing tibial plateau angle coupled with a smaller fat pad width. Of these dogs, 175 were genotyped, and 144,509 polymorphisms were used in a genome-wide association study with both a mixed linear and a multi-locus model. For both models, significant (pgenome <3.46×10-7 for the mixed and< 6.9x10-8 for the multilocus model) associations were found for PC1, tibial diaphyseal length and width, fat pad base length, and femoral and tibial condyle width at LCORL, a known body size-regulating locus. Other body size loci with significant associations were growth hormone 1 (GH1), which was associated with the length of the fat pad base and the width of the tibial diaphysis, and a region on CFAX near IRS4 and ACSL4 in the multilocus model. The tibial plateau angle was associated significantly with a locus on CFA10 in the linear mixed model with nearest candidate genes BET1 and MYH9 and on CFA08 near candidate genes WDHD1 and GCH1. MYH9 has a major role in osteoclastogenesis. Our study indicated that tibial plateau slope is associated with CCLD and a compressed infrapatellar fat pad, a surrogate for stifle osteoarthritis. Because of the association between tibial plateau slope and CCLD, and pending independent validation, these candidate genes for tibial plateau slope may be tested in breeds susceptible to CCLD before they develop disease or are bred.


Assuntos
Ligamento Cruzado Anterior/fisiopatologia , Doenças do Cão/genética , Estudo de Associação Genômica Ampla , Hormônio do Crescimento/genética , Animais , Ligamento Cruzado Anterior/diagnóstico por imagem , Tamanho Corporal/genética , Mapeamento Cromossômico , Coenzima A Ligases/genética , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/fisiopatologia , Cães , Fêmur/diagnóstico por imagem , Fêmur/fisiopatologia , Genótipo , Proteínas Substratos do Receptor de Insulina/genética , Artropatias/genética , Artropatias/fisiopatologia , Artropatias/veterinária , Cadeias Pesadas de Miosina/genética , Osteoartrite/genética , Osteoartrite/fisiopatologia , Osteoartrite/veterinária , Proteínas Repressoras/genética , Tíbia/diagnóstico por imagem , Tíbia/fisiopatologia
7.
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
8.
Adv Exp Med Biol ; 1178: 207-225, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31493229

RESUMO

Growth hormone (GH) is a metabolic hormone that has major functions in the liver, muscle, and adipose tissue (AT). In the past 20 years, numerous studies have demonstrated that decreased growth hormone (GH) action is clearly linked to alterations in longevity. Therefore, it is not surprising that mechanisms underlying the extended longevity of GH-mutant animals include alterations in AT function. This Review aims to describe the basics of AT biology, GH secretion and action, and the effects of altered GH signaling in mice and humans. Lastly, this Review discusses the intersection of GH and AT, and how the influence of GH on AT may play a critical role in determining lifespan and healthspan.


Assuntos
Tecido Adiposo Marrom , Hormônio do Crescimento , Longevidade , Tecido Adiposo Marrom/fisiologia , Tecido Adiposo Branco/fisiologia , Animais , Hormônio do Crescimento/genética , Humanos , Longevidade/fisiologia , Camundongos , Transdução de Sinais
9.
Endocrinology ; 160(11): 2673-2691, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31436800

RESUMO

Isolated growth hormone deficiency type II (IGHD2) is mainly caused by heterozygous splice-site mutations in intron 3 of the GH1 gene. A dominant-negative effect of the mutant GH lacking exon 3 on wild-type GH secretion has been proposed; however, the molecular mechanisms involved are elusive. To uncover the molecular systems underlying GH deficiency in IGHD2, we established IGHD2 model mice, which carry both wild-type and mutant copies of the human GH1 gene, replacing each of the endogenous mouse Gh loci. Our IGHD2 model mice exhibited growth retardation along with intact cellular architecture and mildly activated endoplasmic reticulum stress in the pituitary gland, caused by decreased GH-releasing hormone receptor (Ghrhr) and Gh gene promoter activities. Decreased Ghrhr and Gh promoter activities were likely caused by reduced levels of nuclear CREB3L2, which was demonstrated to stimulate Ghrhr and Gh promoter activity. To our knowledge, this is the first in vivo study to reveal a novel molecular mechanism of GH deficiency in IGHD2, representing a new paradigm that differs from widely accepted models.


Assuntos
Nanismo Hipofisário/etiologia , Hormônio do Crescimento/metabolismo , Receptores de Neuropeptídeos/metabolismo , Receptores de Hormônios Reguladores de Hormônio Hipofisário/metabolismo , Animais , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Nanismo Hipofisário/patologia , Feminino , Hormônio do Crescimento/genética , Humanos , Masculino , Camundongos , Hipófise/metabolismo , Hipófise/ultraestrutura , Regiões Promotoras Genéticas , Receptores de Neuropeptídeos/genética , Receptores de Hormônios Reguladores de Hormônio Hipofisário/genética
10.
J Genet ; 98(2)2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31204710

RESUMO

Screening of trait-associated molecular markers can be used to enhance the efficiency of selective breeding. Previously, we produced the first high-density genetic linkage map for the mandarin fish (Siniperca chuatsi) and identified 11 quantitative-trait loci significantly associated with growth, of which one is located within the growth hormone (GH) gene. To investigate the GH gene polymorphisms and their correlation with growth, the complete sequence was cloned and 32 single-nucleotide polymorphisms (SNPs) and one simple-sequence repeat (SSR) were identified. Of which, eight SNPs (G1-G8) and the SSR (GH-AG)were selected for genotyping and correlation analysis with growth traits in a random population. The results showed that the four novel polymorphicloci (G1, G2, G3 and GH-AG) were significantly correlated with growth traits of mandarin fish (P < 0.05). Of these, G1, G3 and GH-AG showed highly significant correlations with multiple growth traits (P < 0.01) and the combined SNP analysis showed that G1-G3 formed four effective diplotypes (D1-D4), among which D1 was highly significantly greater than D4 (P < 0.01) for some important growth traits. In conclusion, our results show that the four polymorphic loci G1-G3 and GH-AG within the mandarin fish GH gene are significantly correlated with growth traits and could be used as candidate molecular markers for selective breedingof superior varieties of mandarin fish.


Assuntos
Peixes/crescimento & desenvolvimento , Peixes/genética , Hormônio do Crescimento/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Alelos , Animais , Frequência do Gene , Genótipo , Desequilíbrio de Ligação , Locos de Características Quantitativas , Característica Quantitativa Herdável
11.
Fish Physiol Biochem ; 45(5): 1627-1647, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31161532

RESUMO

The 56-day feeding trial was carried out to investigate the effects of dietary tryptophan (Trp) on growth performance, digestive and absorptive enzyme activities, intestinal antioxidant capacity, and appetite and GH-IGF axis-related genes expression of hybrid catfish (Pelteobagrus vachelli♀ × Leiocassis longirostris♂). A total of 864 hybrid catfish (21.82 ± 0.14 g) were fed six different experimental diets containing graded levels of Trp at 2.6, 3.1, 3.7, 4.2, 4.7, and 5.6 g kg-1 diet. The results indicated that dietary Trp increased (P < 0.05) (1) final body weight, percent weight gain, specific growth rate, feed intake, feed efficiency, and protein efficiency ratio; (2) fish body protein, lipid and ash contents, protein, and ash production values; (3) stomach weight, stomach somatic index, liver weight, intestinal weight, length and somatic index, and relative gut length; and (4) activities of pepsin in the stomach; trypsin, chymotrypsin, lipase, and amylase in the pancreas and intestine; and γ-glutamyl transpeptidase, Na+, K+-ATPase, and alkaline phosphatase in the intestine. Dietary Trp decreased malondialdehyde content, increased antioxidant enzyme activities and glutathione content, but downregulated Keap1 mRNA expression, and upregulated the expression of NPY, ghrelin, GH, GHR, IGF1, IGF2, IGF1R, PIK3Ca, AKT1, TOR, 4EBP1, and S6K1 genes. These results indicated that Trp improved hybrid catfish growth performance, digestive and absorptive ability, antioxidant status, and appetite and GH-IGF axis-related gene expression. Based on the quadratic regression analysis of PWG, SGR, and FI, the dietary Trp requirement of hybrid catfish (21.82-39.64 g) was recommended between 3.96 and 4.08 g kg-1 diet (9.4-9.7 g kg-1 of dietary protein).


Assuntos
Apetite/efeitos dos fármacos , Peixes-Gato/genética , Peixes-Gato/fisiologia , Cruzamentos Genéticos , Intestinos/efeitos dos fármacos , Triptofano/farmacologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Antioxidantes/metabolismo , Dieta/veterinária , Digestão/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio do Crescimento/genética , Hormônio do Crescimento/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 , Intestinos/enzimologia , Intestinos/fisiologia , Triptofano/administração & dosagem
12.
Endocr J ; 66(9): 807-816, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31189758

RESUMO

CDK5 regulatory subunit associated protein 1-like 1 (CDKAL1) is a tRNA-modifying enzyme that catalyzes 2-methylthiolation (ms2) and has been implicated in the development of type 2 diabetes (T2D). CDKAL1-mediated ms2 is important for efficient protein translation and regulates insulin biosynthesis in pancreatic cells. Interestingly, an association between T2D and release of growth hormone (GH) has been reported in humans. However, it is unknown whether CDKAL1 is important for hormone production in the pituitary gland. The present study investigated the role of CDKAL1 in GH-producing pituitary adenomas (GHPAs). CDKAL1 activity was suppressed in GHPAs, as evidenced by a decrease in ms2, compared with non-functioning pituitary adenomas (NFPAs), which do not produce specific hormones. Downregulation of Cdkal1 using small interfering and short hairpin RNAs increased the biosynthesis and secretion of GH in rat GH3 cells. Depletion of Cdkal1 increased the cytosolic calcium level via downregulation of DnaJ heat shock protein family (Hsp40) member C10 (Dnajc10), which is an endoplasmic reticulum protein related to calcium homeostasis. This stimulated transcription of GH via upregulation of Pit-1. Moreover, CDKAL1 activity was highly sensitive to proteostatic stress and was upregulated by suppression of this stress. Taken together, these results suggest that dysregulation of CDKAL1 is involved in the pathogenesis of GHPAs, and that modulation of the proteostatic stress response might control CDKAL1 activity and facilitate treatment of GHPAs.


Assuntos
Adenoma/genética , Hormônio do Crescimento/biossíntese , Neoplasias Hipofisárias/genética , tRNA Metiltransferases/fisiologia , Adenoma/metabolismo , Adenoma/patologia , Animais , Células Cultivadas , Estresse do Retículo Endoplasmático/fisiologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Hormônio do Crescimento/genética , Adenoma Hipofisário Secretor de Hormônio do Crescimento/genética , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Adenoma Hipofisário Secretor de Hormônio do Crescimento/patologia , Hormônio do Crescimento Humano/biossíntese , Hormônio do Crescimento Humano/genética , Humanos , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , RNA Interferente Pequeno/farmacologia , Ratos , Resposta a Proteínas não Dobradas/fisiologia , tRNA Metiltransferases/genética
13.
Gen Comp Endocrinol ; 282: 113200, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31199926

RESUMO

Gonadotropin-inhibitory hormone (GnIH) is a multifunctional hypophysiotropic neurohormone and has a stimulatory role in the control of reproduction in the grass puffer. To clarify the neuroendocrine mechanisms underlying the effect of changes in water temperature on reproduction in fish, we previously revealed that, in parallel to gonadal regression, both low and high temperature significantly decreased the expressions of the genes encoding kisspeptin (kiss2), kisspeptin receptor (kiss2r), gonadotropin-releasing hormone 1 (gnrh1) in the brain and gonadotropin (GTH) subunits (fshb and lhb) in the pituitary of sexually mature male grass puffer. In this study, we examined the changes in expression of gnih and GnIH receptor gene (gnihr) in the brain and pituitary along with the genes for growth hormone (gh) and prolactin (prl) in the pituitary of male grass puffer exposed to low temperature (14 °C), normal temperature (21 °C, as initial control) and high temperature (28 °C) conditions for 7 days. The levels of gnih and gnihr mRNAs were significantly decreased in both low and high temperature conditions compared to normal temperature in the brain and pituitary. Similarly, the gh mRNA levels were significantly decreased in both low and high temperature conditions. The prl mRNAs showed no significant changes at high temperature, whereas drastically decreased at low temperature possibly by dysfunctional cold stress. Taken together, the present results suggest that, in addition to the inhibitory effect of temperature changes on the Kiss2/GnRH1/GTH system, the suppression of GnIH/GH system may also be involved in the termination of reproduction by high temperature at the end of breeding season.


Assuntos
Cruzamento , Gonadotropinas/genética , Hormônio do Crescimento/genética , Hormônios Hipotalâmicos/genética , Prolactina/genética , Receptores da Gonadotropina/genética , Takifugu/genética , Temperatura , Animais , Peso Corporal , Encéfalo/metabolismo , Temperatura Baixa , Regulação da Expressão Gênica , Gonadotropinas/metabolismo , Hormônio do Crescimento/metabolismo , Temperatura Alta , Hormônios Hipotalâmicos/metabolismo , Masculino , Hipófise/metabolismo , Prolactina/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores da Gonadotropina/metabolismo , Estações do Ano
14.
Biomed Res Int ; 2019: 5939372, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31073528

RESUMO

Objective: This study aimed to examine the relationship between serum alanine aminotransferase (ALT) and growth hormone (GH) in children and adolescents with short stature. Methods: In this retrospective cohort study, 670 Chinese children and adolescents with short stature were included, and 253 of them received recombinant human GH (rhGH) therapy. Anthropometric and biochemical indicators were measured. GH peak levels were assessed after provocation tests with L-dopa and insulin. The subjects were divided into 3 groups according to the GH peak level. The association between the GH peak and ALT was analyzed. The change of ALT during rhGH therapy was assessed by a generalized additive mixed model. Results: Serum ALT and incidence of ALT elevation were both decreased across the GH tertiles (P = 0.002, 0.012, respectively). A univariate analysis showed that the GH peak was negatively associated with ALT (ß: -0.12; 95%CI: -0.22, -0.02; P = 0.023). Furthermore, multiple linear stepwise regression analysis demonstrated that the GH peak was independently related to ALT after adjusting for other confounding variables (ß: -0.12; 95%CI: -0.24, -0.00; P = 0.042). Besides, mean values of the change in ALT from baseline displayed that, during the early stages of rhGH treatment, serum ALT level indicated a temporary upward trend, but it subsequently gradually decreased (ß: -0.16; 95%CI: -0.23, -0.09; P < 0.001). Conclusions: GH secretion level was strongly negatively correlated with ALT in short children and adolescents. And rhGH therapy could reduce ALT level over time.


Assuntos
Alanina Transaminase/sangue , Nanismo/sangue , Hormônio do Crescimento/sangue , Proteínas Recombinantes/administração & dosagem , Adolescente , Antropometria , Estatura , Criança , China , Nanismo/tratamento farmacológico , Nanismo/fisiopatologia , Feminino , Hormônio do Crescimento/administração & dosagem , Hormônio do Crescimento/genética , Humanos , Insulina/sangue , Levodopa/sangue , Masculino , Proteínas Recombinantes/genética
15.
Endocrinology ; 160(7): 1743-1756, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31099824

RESUMO

In 1997, our laboratory used targeted gene disruption of the GH receptor (GHR) to generate GHR knockout (GHR-/-) mice, which have been used in >127 published studies to help elucidate GH's numerous activities. However, because GH replacement studies cannot be performed using this line, a GH knockout mouse line via targeted disruption of the GH gene is needed. Therefore, we created and characterized GH gene-disrupted (GH-/-) mice. GH-/- mice have severely decreased IGF-1 levels, small body size, and altered body composition with increased adiposity. GH-/- mice are extremely insulin sensitive but glucose intolerant, with a dramatic reduction in pancreatic islet size. Importantly, disruption of the GH gene had profound and depot-specific effects on white adipose tissue (WAT). Subcutaneous WAT from male and female GH-/- mice have significantly larger adipocytes and reduced fibrosis, neither of which occurred in perigonadal WAT, suggesting that GH has a more pronounced effect on subcutaneous WAT. Comparisons of GH-/- mice to previously published data on GHR-/- mice show a remarkably similar phenotype. Finally, we demonstrate that GH-/- mice are responsive to GH treatment, as shown by changes to serum IGF-1 levels; body length, weight, and composition; and insulin sensitivity. This study not only provides characterization of the first mouse line with targeted mutation of the GH gene but also indicates that GH gene disruption dramatically influences fibrosis of subcutaneous WAT.


Assuntos
Adipócitos/metabolismo , Hormônio do Crescimento/genética , Resistência à Insulina/fisiologia , Gordura Subcutânea/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Composição Corporal/fisiologia , Feminino , Fibrose/genética , Fibrose/metabolismo , Hormônio do Crescimento/metabolismo , Ilhotas Pancreáticas/metabolismo , Masculino , Camundongos , Camundongos Knockout
16.
BMC Genomics ; 20(1): 336, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053056

RESUMO

BACKGROUND: Triploid coho salmon are excellent models for studying gene dosage and the effects of increased cell volume on gene expression. Triploids have an additional haploid genome in each cell and have fewer but larger cells than diploid coho salmon to accommodate the increased genome size. Studying gene expression in triploid coho salmon provides insight into how gene expression may have been affected after the salmonid-specific genome duplication which occurred some 90 MYA. Triploid coho salmon are sterile and consequently can live longer and grow larger than diploid congeners in many semelparous species (spawning only once) because they never reach maturity and post-spawning mortality is averted. Triploid fishes are also of interest to the commercial sector (larger fish are more valuable) and to fisheries management since sterile fish can potentially minimize negative impacts of escaped fish in the wild. RESULTS: The vast majority of genes in liver tissue had similar expression levels between diploid and triploid coho salmon, indicating that the same amount of mRNA transcripts were being produced per gene copy (positive gene dosage effects) within a larger volume cell. Several genes related to nutrition and compensatory growth were differentially expressed between diploid and triploid salmon, indicating that some loci are sensitive to cell size and/or DNA content per cell. To examine how robust expression between ploidies is under different conditions, a genetic/metabolic modifier in the form of different doses of a growth hormone transgene was used to assess gene expression under conditions that the genome has not naturally experienced or adapted to. While many (up to 1400) genes were differentially expressed between non-transgenic and transgenic fish, relatively few genes were differentially expressed between diploids and triploids with similar doses of the transgene. These observations indicate that the small effect of ploidy on gene expression is robust to large changes in physiological state. CONCLUSIONS: These findings are of interest from a gene regulatory perspective, but also valuable for understanding phenotypic effects in triploids, transgenics, and triploid transgenics that could affect their utility in culture conditions and their fitness and potential consequences of release into nature.


Assuntos
Animais Geneticamente Modificados/genética , Diploide , Regulação da Expressão Gênica , Hormônio do Crescimento/administração & dosagem , Fígado/metabolismo , Oncorhynchus kisutch/genética , Triploidia , Animais , Animais Geneticamente Modificados/crescimento & desenvolvimento , Animais Geneticamente Modificados/metabolismo , Hormônio do Crescimento/genética , Oncorhynchus kisutch/crescimento & desenvolvimento , Oncorhynchus kisutch/metabolismo , Transgenes
17.
Dev Cell ; 49(4): 618-631.e5, 2019 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-30982661

RESUMO

MicroRNAs (miRNAs) are processed from primary miRNA transcripts (pri-miRNAs), many of which are annotated as long noncoding RNAs (lncRNAs). We assessed whether MIR205HG, the host gene for miR-205, has independent functions as an lncRNA. Comparing mice with targeted deletions of MIR205HG and miR-205 revealed a functional role for the lncRNA in the anterior pituitary. Mice lacking MIR205HG had a temporal reduction in Pit1, growth hormone, and prolactin. This was mediated, in part, through the ability of this lncRNA to bind and regulate the transcriptional activity of Pit1 in conjunction with Zbtb20. Knockdown of MIR205HG in lactotropes decreased the expression of Pit1, Zbtb20, prolactin, and growth hormone, while its overexpression enhanced the levels of these transcripts. The effects of MIR205HG on the pituitary were independent of miR-205. The data support a role for MIR205HG as an lncRNA that regulates growth hormone and prolactin production in the anterior pituitary.


Assuntos
Hormônio do Crescimento/biossíntese , MicroRNAs/metabolismo , Adeno-Hipófise/metabolismo , Prolactina/biossíntese , RNA Longo não Codificante/metabolismo , Animais , Hormônio do Crescimento/genética , Hormônio do Crescimento/metabolismo , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Prolactina/genética , Prolactina/metabolismo , RNA Longo não Codificante/genética , Ratos , Fator de Transcrição Pit-1/genética , Fator de Transcrição Pit-1/metabolismo , Transcriptoma
18.
Proc Natl Acad Sci U S A ; 116(15): 7449-7454, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30910968

RESUMO

When mice are subjected to 60% calorie restriction for several days, they lose nearly all of their body fat. Although the animals lack energy stores, their livers produce enough glucose to maintain blood glucose at viable levels even after a 23-hour fast. This adaptation is mediated by a marked increase in plasma growth hormone (GH), which is elicited by an increase in plasma ghrelin, a GH secretagogue. In the absence of ghrelin, calorie-restricted mice develop hypoglycemia, owing to diminished glucose production. To determine the site of GH action, in the current study we used CRISPR/Cas9 and Cre recombinase technology to produce mice that lack GH receptors selectively in liver (L-Ghr -/- mice) or in adipose tissue (Fat-Ghr-/- mice). When subjected to calorie restriction and then fasted for 23 hours, the L-Ghr -/- mice, but not the Fat-Ghr-/- mice, developed hypoglycemia. The fall in blood glucose in L-Ghr-/- mice was correlated with a profound drop in hepatic triglycerides. Hypoglycemia was prevented by injection of lactate or octanoate, two sources of energy to support gluconeogenesis. Electron microscopy revealed extensive autophagy in livers of calorie-restricted control mice but not in L-Ghr -/- mice. We conclude that GH acts through its receptor in the liver to activate autophagy, preserve triglycerides, enhance gluconeogenesis, and prevent hypoglycemia in calorie-restricted mice, a model of famine.


Assuntos
Autofagia , Glicemia/metabolismo , Restrição Calórica , Hormônio do Crescimento/sangue , Hipoglicemia/sangue , Fígado/metabolismo , Inanição/sangue , Animais , Glicemia/genética , Doença Crônica , Modelos Animais de Doenças , Hormônio do Crescimento/genética , Hipoglicemia/genética , Fígado/patologia , Camundongos , Camundongos Knockout , Inanição/genética , Inanição/patologia
19.
Anim Sci J ; 90(4): 493-503, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30706583

RESUMO

This study was designed to estimate dietary energy level on intramuscular fat (IMF) deposition in Simmental × Yellow breed cattle. Results showed that ultimate weight and average daily gain in high and medium energy groups were significantly higher than low-energy group, yet feed conversion ratio was significantly lower. IMF content was significantly increased by dietary energy increasing, whereas longissimus muscle shear force significantly decreased. Serum-free fatty acids, triglycerides and glucose significantly increased by dietary energy increasing, whereas growth hormone (GH) significantly decreased. Enzyme activities of lipoprotein lipase (LPL), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) significantly increased by dietary energy increasing, whereas hormone-sensitive lipase (HSL) and carnitine palmitoyltransferase-1 (CPT-1) significantly diminished. Peroxisome proliferator-activated receptor γ, sterol regulatory element-binding protein 1, stearoyl-CoA desaturase, adipocyte-fatty acid-binding proteins, ACC, LPL, and FAS gene or protein expression significantly increased by dietary energy increasing, whereas HSL, CPT-1, and GH gene or protein expression significantly decreased. These results indicated that high dietary energy promoting IMF deposition is mainly by downregulating pituitary GH gene expression, decreasing serum GH concentration, increasing lipogenic genes levels of mRNA, enzyme activities and protein expression, and decreasing lipolytic genes levels of mRNA, enzyme activities, and protein expression.


Assuntos
Tecido Adiposo/metabolismo , Cruzamento , Bovinos/genética , Bovinos/metabolismo , Dieta/veterinária , Ingestão de Energia/fisiologia , Expressão Gênica , Hormônio do Crescimento/genética , Hormônio do Crescimento/metabolismo , Músculo Esquelético/metabolismo , Animais , Regulação para Baixo , Ingestão de Energia/genética , Lipogênese/genética , Lipólise/genética , Lipase Lipoproteica/genética , Lipase Lipoproteica/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ganho de Peso
20.
Sci Total Environ ; 662: 834-841, 2019 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-30795479

RESUMO

The potential endocrine disruption of neonicotinoids poses a significant threat to the survival of small farmland lizards. We systematically evaluated the distribution, metabolism, and toxicity of three neonicotinoids (dinotefuran, thiamethoxam, and imidacloprid) in the Eremias argus during a 35-day oral administration exposure. Lizards could quickly transfer and store neonicotinoids into the scale and eliminated through molting. Dinotefuran was most prone to accumulation in lizard tissues, followed by thiamethoxam, and imidacloprid was generally present in the form of its terminal metabolite 6-chloropyridinyl acid. Exposure to dinotefuran resulted in hepatic oxidative stress damage, decreased plasma growth hormone concentration, and down-regulation of ghr, igf1 and igfbp2 gene expression. These indicated that dinotefuran might have potential growth inhibition toxicity to lizards. Although imidacloprid caused severe liver oxidative stress damage, the effect of imidacloprid on GH/IGF axis was not obvious. Compared to dinotefuran and imidacloprid, thiamethoxam had the least damage to liver and minimal impact on GH/IGF axis. This study verified the possible damage of neonicotinoids to lizard liver and the interference of GH/IGF axis for the first time.


Assuntos
Poluentes Ambientais/toxicidade , Inseticidas/toxicidade , Fígado/efeitos dos fármacos , Lagartos/metabolismo , Neonicotinoides/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , China , Poluentes Ambientais/farmacocinética , Fazendas , Feminino , Expressão Gênica/efeitos dos fármacos , Hormônio do Crescimento/genética , Hormônio do Crescimento/metabolismo , Inseticidas/farmacocinética , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Fígado/metabolismo , Fígado/patologia , Lagartos/genética , Lagartos/crescimento & desenvolvimento , Masculino , Modelos Teóricos , Neonicotinoides/farmacocinética , Distribuição Tecidual
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