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1.
Theriogenology ; 141: 180-185, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31550601

RESUMO

The aim of this research was to evaluate the effect of recombinant bovine somatotropin (bST) on pregnancy per artificial insemination (P/AI), cellular composition of the corpus luteum (CL) and endometrial gland morphometry. In Experiment 1, Nelore cows (n = 587) received a fixed-time artificial insemination (FTAI) protocol and, at insemination, received 0, 250 or 500 mg of bST subcutaneously (SC). In Experiment 2, Nelore cows (n = 243) received 0 or 500 mg of bST, SC, on D7 (D0 = day of FTAI). Blood samples were collected on D7 and D16 to measure progesterone (P4) concentrations. In Experiments 1 and 2, pregnancy diagnosis was performed 30 days after FTAI. In Experiment 3, Nelore heifers (n = 20) received a FTAI protocol, but were not inseminated, and on D0 (ovulation day), they received 0 (bST 0; n = 9) or 500 mg of bST (bST 500; n = 11), SC. The heifers were slaughtered on D15 (D0 = ovulation day), at which time the CL was evaluated for diameter, weight, a percentage of large (LLC) and small (SLC) luteal cells, and the concentration of progesterone in plasma measured. The number, perimeter and area of superficial and deep endometrial glands were evaluated. There was no difference in P/AI when bST was applied on D0 and D7. In Experiment 1, P/AI did not differ among treatments, with 59.28% (115/194), 58.38% (115/197) and 65.82% (129/196) for the bST 0, 250 and 500 treatments, respectively. In Experiment 2, P/AI did not differ between treatments, with 57.3% (71/124) and 60.5% (62/119) for the bST 0 and 500 treatments, respectively. Plasma progesterone concentrations on D16 was greater in the bST 500 (11.63 ±â€¯0.84 ng/mL) than bST 0 (9.83 ±â€¯0.88 ng/mL). In Experiment 3, there was no difference in ovarian diameter and weight, CL diameter, percentage of SLC, P4 concentrations and endometrial gland morphology. Heifers in the bST 500 treatment had heavier CL (3.11 ±â€¯0.32 vs. 2.25 ±â€¯0.20 g); however, the bST 0 treatment heifers had a greater percentage of LLC than did the bST 500 treatment (13.72 ±â€¯1.16% vs. 8.60 ±â€¯1.52). It was concluded that the doses of bST used in this study do not increase P/AI; however, they do cause changes in P4 concentration and the cellular composition of the CL.


Assuntos
Bovinos , Corpo Lúteo/citologia , Endométrio/anatomia & histologia , Hormônio do Crescimento/farmacologia , Inseminação Artificial/veterinária , Animais , Endométrio/fisiologia , Sincronização do Estro , Feminino , Hormônio do Crescimento/administração & dosagem , Gravidez , Proteínas Recombinantes
2.
Int. j. morphol ; 37(4): 1416-1421, Dec. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1040147

RESUMO

The indiscriminate use of anabolic steroids in gyms has been growing in a generalized way, among which, the most common is growth hormone (GH). In the short term GH may potentiate muscle growth, especially when taken in combination with resistance training. However, the effects of this hormone are not yet fully understood in the literature, especially in relation to collagen properties. The objective of this study was to evaluate the effect of the application of growth hormone (GH) and resistance training (RT) on the collagen properties of femoral bone tissue using Raman Spectroscopy. In this study 40 male rats were randomly distributed into four groups (n=10): control (C), control and GH application (GH), resistance training (T), and resistance training and GH application (GHT). The training consisted of four series of 10 water jumps, performed three times a week, with an overload corresponding to 50 % of body weight and duration of four weeks. GH was applied at a dosage of 0.2 IU/Kg (0.067 mg/kg) to each animal, three times a week, every other day. The animals were euthanized and the right femurs were collected for analysis of bone structure. Raman spectroscopy (RS) was used to observe the following compounds from their respective bands: type I collagen (662 cm-1), amide III (1243 cm-1), proteins including type I collagen (1278 cm-1), woven collagen (1322 cm-1), association of collagen, phospholipids, nucleic acid, and phosphate (1330 cm-1), and collagen and protein deformation (1448 cm-1). The results demonstrated an increase in the collagen properties in all analyzed variables, however, the T group presented a statistically significant difference (p<0.05). It is possible to conclude that isolated physical training was shown to be more efficient than when combined with the application of GH to increase the collagen properties of the femoral bone tissue.


El uso indiscriminado de anabolizantes en los gimnasios ha aumentado de forma generalizada, entre éstos la hormona de crecimiento (HC) es una de las más utilizadas, y a corto plazo puede potencializar el crecimiento muscular, principalmente cuando es realizado en combinación con el entrenamiento de fuerza. Sin embargo, los efectos de esta hormona aún no están totalmente esclarecidos en la literatura, especialmente en relación a las propiedades colágenas. El objetivo del estudio fue evaluar el efecto de la aplicación del HC y entrenamiento de fuerza (E) en las propiedades colágenas del tejido óseo femoral a partir de la utilización de la espectroscopía Raman. Se usaron 40 ratas Wistar distribuidos en cuatro grupos (n=10): control (C), control y aplicación del HC (HCC), entrenamiento de fuerza (E) y entrenamiento de fuerza y aplicación del HC (THC). El entrenamiento fue compuesto por cuatro series de 10 saltos acuáticos, realizados tres veces por semana, con sobrecarga correspondiente a 50 % del peso corporal y duración de cuatro semanas. El HC fue aplicado en una dosificación de 0,2 UI/Kg (0,067 mg/kg) en cada animal, tres veces por semana, en días no consecutivos. Los animales fueran eutanasiados y se retiró el fémur derecho para realización del análisis de la estructura ósea. La espectroscopía Raman (ER) fue utilizada para observar los siguientes compuestos a partir de las respectivas bandas: colágeno tipo I (662 cm-1), amida III (1243 cm1), proteínas, incluido colágeno tipo I (1278 cm-1), colágeno retorcido (1322 cm-1), asociación de colágeno, fosfolípidos, ácidos nucleicos y fosfato (1330 cm-1), deformación de colágeno y proteína (1448 cm-1). Hubo aumento en las propiedades colágenas en todas las variables analizadas, sin embargo, solamente el grupo E demostró una diferencia estadísticamente significativa (p<0,05). En conclusión, para el aumento de las propiedades colágenas del tejido óseo femoral, el entrenamiento físico aislado es más eficiente que el entrenamiento combinado con el uso de HC.


Assuntos
Animais , Masculino , Ratos , Resistência Física/fisiologia , Hormônio do Crescimento/farmacologia , Fêmur/efeitos dos fármacos , Fêmur/fisiologia , Hormônio do Crescimento/administração & dosagem , Exercício Físico/fisiologia , Colágeno/efeitos dos fármacos , Ratos Wistar , Microscopia/métodos
3.
Int J Mol Sci ; 20(18)2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31509934

RESUMO

In addition to its role as an endocrine messenger, growth hormone (GH) also acts as a neurotrophic factor in the central nervous system (CNS), whose effects are involved in neuroprotection, axonal growth, and synaptogenic modulation. An increasing amount of clinical evidence shows a beneficial effect of GH treatment in patients with brain trauma, stroke, spinal cord injury, impaired cognitive function, and neurodegenerative processes. In response to injury, Müller cells transdifferentiate into neural progenitors and proliferate, which constitutes an early regenerative process in the chicken retina. In this work, we studied the long-term protective effect of GH after causing severe excitotoxic damage in the retina. Thus, an acute neural injury was induced via the intravitreal injection of kainic acid (KA, 20 µg), which was followed by chronic administration of GH (10 injections [300 ng] over 21 days). Damage provoked a severe disruption of several retinal layers. However, in KA-damaged retinas treated with GH, we observed a significant restoration of the inner plexiform layer (IPL, 2.4-fold) and inner nuclear layer (INL, 1.5-fold) thickness and a general improvement of the retinal structure. In addition, we also observed an increase in the expression of several genes involved in important regenerative pathways, including: synaptogenic markers (DLG1, NRXN1, GAP43); glutamate receptor subunits (NR1 and GRIK4); pro-survival factors (BDNF, Bcl-2 and TNF-R2); and Notch signaling proteins (Notch1 and Hes5). Interestingly, Müller cell transdifferentiation markers (Sox2 and FGF2) were upregulated by this long-term chronic GH treatment. These results are consistent with a significant increase in the number of BrdU-positive cells observed in the KA-damaged retina, which was induced by GH administration. Our data suggest that GH is able to facilitate the early proliferative response of the injured retina and enhance the regeneration of neurite interconnections.


Assuntos
Hormônio do Crescimento/farmacologia , Ácido Caínico/toxicidade , Regeneração/efeitos dos fármacos , Retina/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Fator Neurotrófico Derivado do Encéfalo/genética , Embrião de Galinha , Galinhas , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Neurogênese/genética , Neurogênese/fisiologia , Fármacos Neuroprotetores/farmacologia , Neurotoxinas/toxicidade , Receptor Notch1/genética , Regeneração/genética , Regeneração/fisiologia , Retina/metabolismo , Retina/fisiopatologia , Fatores de Transcrição SOXB1/genética
4.
Int J Mol Sci ; 20(18)2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31491959

RESUMO

Growth hormone secretagogues (GHS) are a family of synthetic molecules, first discovered in the late 1970s for their ability to stimulate growth hormone (GH) release. Many effects of GHS are mediated by binding to GHS-R1a, the receptor for the endogenous hormone ghrelin, a 28-amino acid peptide isolated from the stomach. Besides endocrine functions, both ghrelin and GHS are endowed with some relevant extraendocrine properties, including stimulation of food intake, anticonvulsant and anti-inflammatory effects, and protection of muscle tissue in different pathological conditions. In particular, ghrelin and GHS inhibit cardiomyocyte and endothelial cell apoptosis and improve cardiac left ventricular function during ischemia-reperfusion injury. Moreover, in a model of cisplatin-induced cachexia, GHS protect skeletal muscle from mitochondrial damage and improve lean mass recovery. Most of these effects are mediated by GHS ability to preserve intracellular Ca2+ homeostasis. In this review, we address the muscle-specific protective effects of GHS mediated by Ca2+ regulation, but also highlight recent findings of their therapeutic potential in pathological conditions characterized by skeletal or cardiac muscle impairment.


Assuntos
Sinalização do Cálcio/efeitos dos fármacos , Hormônio do Crescimento/farmacologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Secretagogos/farmacologia , Animais , Humanos
5.
Nutrients ; 11(8)2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31426533

RESUMO

Growth hormone (GH) and glutamine (Gln) stimulate the growth of the intestinal mucosa. GH activates the proliferation of intestinal stem cells (ISCs), enhances the formation of crypt organoids, increases ISC stemness markers in the intestinal organoids, and drives the differentiation of ISCs into Paneth cells and enterocytes. Gln enhances the proliferation of ISCs and increases crypt organoid formation; however, it mainly acts on the post-proliferation activity of ISCs to maintain the stability of crypt organoids and the intestinal mucosa, as well as to stimulate the differentiation of ISCs into goblet cells and possibly Paneth cells and enteroendocrine cells. Since GH and Gln have differential effects on ISCs. Their use in combination may have synergistic effects on ISCs. In this review, we summarize the evidence of the actions of GH and/or Gln on crypt cells and ISCs in the literature. Overall, most studies demonstrated that GH and Gln in combination exerted synergistic effects to activate the proliferation of crypt cells and ISCs and enhance crypt organoid formation and mucosal growth. This treatment influenced the proliferation of ISCs to a similar degree as GH treatment alone and the differentiation of ISCs to a similar degree as Gln treatment alone.


Assuntos
Glutamina/farmacologia , Hormônio do Crescimento/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Diferenciação Celular , Proliferação de Células , Sinergismo Farmacológico , Humanos , Mucosa Intestinal/citologia , Mucosa Intestinal/crescimento & desenvolvimento , Organoides/efeitos dos fármacos , Organoides/crescimento & desenvolvimento , Células-Tronco/fisiologia
6.
PLoS One ; 14(7): e0204384, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31260450

RESUMO

Previous studies have indicated that bone morphogenetic protein (BMP) 6 may play an important role in skeletal system development and progression. However, the mechanism underlying the effects of BMP6 in cartilage cell proliferation and differentiation remains unknown. In this study, cartilage cells were isolated from shanks of chicken embryos and treated with different concentrations of Growth Hormone. Cell proliferation potential was assessed using real-time polymerase chain reaction (RT-PCR), western blotting and CCK-8 assays in vitro. The results showed that at 48 h, the Collagen II and BMP6 expression levels in 50 ng/µl GH-treated cartilage cells were significantly higher than in groups treated with 100 ng/µl or 200 ng/µl GH. We further observed that knockdown of BMP6 in cartilage cells led to significantly decreased expression mRNAs and proteins of Collagen II and Collagen X. Moreover, the suppression of BMP6 expression by a specific siRNA led to significantly decreased expression mRNA levels of IGF1R, JAK2, PKC, PTH, IHH and PTHrP and decreased protein levels of PKC, IHH and PTHrP. Taken together, our data suggest that BMP6 may play a critical role in chicken cartilage cell proliferation and differentiation through the regulation of IGF1, JAK2, PKC, PTH, and IHH-PTHrP signaling pathways.


Assuntos
Proteínas Aviárias/metabolismo , Proteína Morfogenética Óssea 6/metabolismo , Cartilagem/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Hormônio do Crescimento/farmacologia , Animais , Cartilagem/citologia , Células Cultivadas , Embrião de Galinha , Relação Dose-Resposta a Droga , RNA Mensageiro/biossíntese , Transdução de Sinais/efeitos dos fármacos
7.
Endocr Rev ; 40(4): 1163-1185, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31180479

RESUMO

GH is banned by the World Anti-Doping Agency as a performance-enhancing anabolic agent. Doping with GH likely began in the early 1980s and became more prevalent with the advent of recombinant technology well before any scientific evidence of benefit. The expectation that GH improves physical function stems from its anabolic and lipolytic properties. Athletic performance depends on muscle strength and the energy required to power muscle function. In recreational athletes, GH selectively improves anaerobic sprint capacity but has not been proven to significantly enhance muscle strength, power, or maximum rate of oxygen consumption. GH is secreted as a family of isoform peptides in a pulsatile manner reflecting intermittent secretion and rapid clearance. Its anabolic actions are largely mediated by IGF-I, which stimulates whole-body protein synthesis, including skeletal muscle and collagen proteins. Two methods have been validated for detecting GH abuse in athletes. The first (the isoform method) is based on distinguishing pure recombinant 22-kDa GH from the heterogeneous isoforms secreted from the pituitary. The second (the marker method) is based on measuring blood levels of GH-responsive proteins, specifically IGF-I and the N-terminal propeptide of type III collagen (P-III-NP). Only a handful of athletes have been caught since the implementation of GH doping tests in 2004. The low rate likely reflects the limitation of in-competition testing using current methods. Improved detection rates may be achieved by more out-of-competition testing, introducing athletes' biological passports, and the development of novel methods. Governance, operational, technical, and political factors influence the effectiveness of an anti-doping program.


Assuntos
Doping nos Esportes , Hormônio do Crescimento/análise , Hormônio do Crescimento/farmacologia , Detecção do Abuso de Substâncias , Humanos
8.
J Dairy Sci ; 102(8): 7522-7535, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31155243

RESUMO

The liver becomes resistant to growth hormone before parturition in dairy cows (uncoupling of the somatotropic axis). However, the mechanism of growth hormone insensitivity has not been fully described. The aim of the present study was to improve a previous model of adult bovine hepatocytes in a sandwich culture system to ensure growth hormone receptor (GHR) expression. First, we modified the protocol for hepatocyte retrieval and tested the effect of short (18 min) and long (up to 30 min) warm ischemia on hepatocyte viability. Second, we used medium additives that affect GHR expression in vivo-insulin (INS), dexamethasone (DEX), both (INS+DEX), or no hormone additives (CTRL)-to ensure the functionality of hepatocytes, as measured by lactate dehydrogenase activity and urea concentration in the medium. We also used reverse transcriptase PCR of hepatocytes to evaluate expression of albumin (ALB), hepatocyte nuclear factor 4α (HNF4A), nuclear factor-κ-B-inhibitor α (NFKBIA), cytosolic phosphoenolpyruvate carboxykinase (PCK1), and vimentin (VIM) mRNA. Moreover, we analyzed the expression of GHRtot (GHR), GHR1A, insulin-like growth factor-1 (IGF1), and IGF binding protein-2 (IGFBP2) in response to exposure to media with the different compositions. Modification of the protocol (changes in rinsing and perfusion times, buffer composition, and the volume and standardization of collagenase) led to increased cell counts and cell viability. Short warm ischemia with the modified protocol significantly increased cell count (4.7 × 107 ± 1.9 × 107 vs. 3.5 × 106 ± 1.5 × 106 vital cells/g of liver) and viability (79.1 ± 8.4 vs. 37.1 ± 8.9%). Therefore, we gathered hepatocytes from the liver after short warm ischemia with the modified protocol. For these hepatocytes, lactate dehydrogenase activity was lower in media with INS and with DEX than in media with INS+DEX or CTRL; urea concentrations were highest at d 4 for INS+DEX. As well, HNF4A and ALB were more highly expressed in hepatocytes cultured with INS and INS+DEX than in those cultured with DEX or CTRL, and the substitution of DEX suppressed VIM and NFKBIA expression but increased PCK1 expression. The expression of GHR, GHR1A, and IGF1 was suppressed by dexamethasone (DEX and INS+DEX), whereas INS distinctly increased GHR, GHR1A, and IGF1 mRNA expression. Hepatocytes in a sandwich culture showed influenceable GHR expression; this study provides a model that can be used in studies examining factors that influence the expression and signal transduction of GHR in dairy cows.


Assuntos
Bovinos/genética , Hepatócitos/metabolismo , Fígado/citologia , Receptores da Somatotropina/genética , Animais , Bovinos/metabolismo , Células Cultivadas , Dexametasona/farmacologia , Feminino , Hormônio do Crescimento/farmacologia , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/análogos & derivados , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Gravidez , Cultura Primária de Células , Receptores da Somatotropina/metabolismo , Vimentina/genética , Vimentina/metabolismo
9.
Gen Comp Endocrinol ; 281: 137-144, 2019 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-31176753

RESUMO

The insulin-like growth factor (IGF) system plays a pivotal role in the regulation of growth, and IGF binding proteins (IGFBPs) are important regulatory factors in the IGF system. Generally, IGFBPs inhibit IGF actions by preventing its binding to receptors. Under some conditions, the IGFBPs can also enhance IGF actions. IGFBP1 is generally inhibitory to IGFI. In this study, the grouper (Epinephelus coioides) igfbp1 (MK621003) gene was cloned from the liver. The sequence of igfbp1 cDNA was 1055 bp and contained a 5'UTR of 127 bp and a 3'UTR of 247 bp, and the ORF of grouper igfbp1 was 741 bp, encoding 246 amino acids. The tissue distribution results showed that igfbp1 has a higher expression in the liver. In the nutritional status experiment, igfbp1 expression was significantly increased in the liver after 7 days of fasting and was markedly decreased after refeeding. In in vitro experiments, igfbp1 expression in grouper primary hepatocytes was significantly inhibited by recombinant grouper Gh (growth hormone) in a dose-dependent manner. Additionally, igfbp1 expression decreased in grouper primary hepatocytes upon incubation with insulin. This is the first report describing grouper igfbp1, and these findings contribute to understanding the roles of IGFBP1 in metabolism and growth in grouper.


Assuntos
Bass/genética , Hormônio do Crescimento/farmacologia , Hepatócitos/metabolismo , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Insulina/farmacologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Células Cultivadas , DNA Complementar/genética , Feminino , Hepatócitos/efeitos dos fármacos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/química , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Filogenia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Tecidual
10.
Fish Physiol Biochem ; 45(3): 1083-1090, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31093852

RESUMO

A comparison of the efficacy of salmon and bovine growth hormone to stimulate growth of coho salmon juveniles was performed. Oncorhynchus nerka (sockeye salmon) type II growth hormone (nGH2) was produced using a bacterial expression system, yielding approximately 25 mg of refolded recombinant protein per litre of cells. The purified nGH2 and bovine growth hormone (bGH) were tested in juvenile O. kisutch (coho salmon) over 24 weeks. Weekly intraperitoneal injections of 0.1 and 0.5 µg/g nGH2 resulted in a dose-dependent increase in weight and fork length compared to control fish injected with bovine serum albumin (BSA). Application of 0.5 µg/g bGH resulted in the same stimulation of growth as did 0.5 µg/g nGH2, indicating these proteins were equipotent. Following 6 weeks of treatment and a subsequent rest period of 7 weeks, coho salmon were further treated with bGH at 0.5 µg/g. A prior treatment with bGH did not reduce growth-promoting activity of bGH in subsequent treatments. Throughout the experiment, condition factor decreased at similar rates for all treatment groups. These data show that bGH, which is widely available, can be used to elevate growth rate in juvenile salmon comparably to homologous GH, and validate the use of bGH in physiological or ecological experiments where rapid growth is desired compared to that seen in wild type.


Assuntos
Hormônio do Crescimento/farmacologia , Oncorhynchus kisutch/crescimento & desenvolvimento , Animais , Relação Dose-Resposta a Droga , Hormônio do Crescimento/administração & dosagem , Distribuição Aleatória
11.
J Anim Sci ; 97(6): 2433-2440, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31066897

RESUMO

The goal of this project was to determine if increasing insulin-like growth factor-1 (IGF-1) concentrations in late pregnancy can stimulate mammogenesis in gilts. Yorkshire × Landrace gilts of a similar body weight (BW; 196.2 ± 6.2 kg) on day 89 of gestation were separated in 2 groups, namely, controls (CTL, n = 17) that were injected with sterile water, and porcine somatotropin-treated (pST, n = 20) that received injections of 5 mg of pST (Reporcin). Injections were given daily from days 90 to 109 of gestation and gilts were slaughtered on day 110 to collect mammary glands for compositional analyses. Blood samples were obtained on days 89, 96, 103, and 109 of gestation to measure IGF-1, free fatty acids (FFA), urea, glucose, and insulin concentrations. Treated gilts gained more BW (22.7 vs. 18.2 kg, P < 0.05) and lost more backfat (P < 0.05) than CTL gilts during the treatment period. There was a treatment × day effect (P < 0.01) on IGF-1, glucose, and urea concentrations. Concentrations of IGF-1 increased 4-fold (P < 0.01) in pST compared with CTL gilts on days 96, 103, and 109 of gestation. Insulin values were also greater on days 96 (P < 0.01) and 103 (P = 0.01), and tended to be greater (P < 0.10) on day 109 of gestation in pST gilts. Glucose was greater in pST than CTL gilts on days 96 (P < 0.01), 103 (P < 0.01), and 109 (P = 0.01). Concentrations of urea were lower (P < 0.01) on days 96, 103, and 109 of gestation in gilts receiving pST injections, and FFA was not altered by treatment on any sampling day (P > 0.10). Injections of pST did not affect mammary extraparenchymal tissue weight (P > 0.10) but increased mammary parenchymal mass (1922 vs. 1576 ± 124 g, P < 0.05). The composition of parenchymal tissue was also altered by treatment. Mammary parenchyma from pST gilts contained more (P < 0.05) protein, DNA and RNA and less fat (P < 0.05) and dry matter (P < 0.01) than that from CTL gilts. These findings provide a clear demonstration that increasing circulating IGF-1 in late-pregnant gilts can stimulate mammary development both in terms of total parenchymal mass and of parenchymal tissue composition.


Assuntos
Hormônio do Crescimento/farmacologia , Glândulas Mamárias Animais/efeitos dos fármacos , Suínos/fisiologia , Animais , Feminino , Hormônio do Crescimento/administração & dosagem , Gravidez , RNA/metabolismo
12.
Endocrinology ; 160(6): 1439-1447, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31002310

RESUMO

DNA damage occurs as a result of environmental insults and aging and, if unrepaired, may lead to chromosomal instability and tumorigenesis. Because GH suppresses ataxia-telangiectasia mutated kinase phosphorylation, decreases DNA repair, and increases DNA damage accumulation, we elucidated whether GH effects on DNA damage are mediated through induced IGF-1. In nontumorous human colon cells, GH, but not IGF-1, increased DNA damage. Stably disrupted IGF-1 receptor (IGF-1R) by lentivirus-expressing short hairpin RNA in vitro or treatment with the IGF-1R phosphorylation inhibitor picropodophyllotoxin (PPP) in vitro and in vivo led to markedly induced GH receptor (GHR) abundance, rendering cells more responsive to GH actions. Suppressing IGF-1R triggered DNA damage in both normal human colon cells and three-dimensional human intestinal organoids. DNA damage was further increased when cells with disrupted IGF-1R were treated with GH. Because GH induction of DNA damage accumulation appeared to be mediated not by IGF-1R but probably by more abundant GH receptor expression, we injected athymic mice with GH-secreting xenografts and then treated them with PPP. In these mice, high circulating GH levels were associated with increased colon DNA damage despite disrupted IGF-1R activity (P < 0.01), whereas GHR levels were also induced. Further confirming that GH effects on DNA damage are directly mediated by GHR signaling, GHR-/- mice injected with PPP did not show increased DNA damage, whereas wild-type mice with intact GHR exhibited increased colon DNA damage in the face of IGF-1 signaling suppression. The results indicate that GH directly induces DNA damage independent of IGF-1.


Assuntos
Colo/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Hormônio do Crescimento/farmacologia , Fator de Crescimento Insulin-Like I/farmacologia , Animais , Linhagem Celular Tumoral , Colo/metabolismo , Relação Dose-Resposta a Droga , Humanos , Camundongos , Camundongos Knockout , Fosforilação/efeitos dos fármacos , Receptor IGF Tipo 1/antagonistas & inibidores , Receptor IGF Tipo 1/metabolismo , Receptores da Somatotropina/genética , Receptores da Somatotropina/metabolismo , Transdução de Sinais/efeitos dos fármacos
13.
Gynecol Endocrinol ; 35(9): 787-791, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30907187

RESUMO

To investigate the clinical efficacy of growth hormone (GH) in normal response patients with poor embryo quality in previous in vitro fertilization cycles. A total of 1562 infertile women were enrolled in this matched case-control study: 781 women were treated with GH (study group), whereas 781 matched patients were treated without GH (control group). GH was administered by a daily subcutaneous injection of 2 or 4 IU started from either D2 of the previous cycle (6 weeks GH pretreatment) or the initial day of controlled ovarian stimulation (2 weeks GH pretreatment) until hCG trigger. The study group was further divided into four subgroups: 2 IU-6 weeks GH pretreatment, 4 IU-6 weeks GH pretreatment, 2 IU-2 weeks GH pretreatment, and 2 IU-4 weeks GH pretreatment. Patients receiving GH showed significantly lower Gn dosage. The total number of oocytes retrieved, embryos formed, endometrial thickness on hCG day were significantly higher with GH. 2PN rate and high-quality embryo rate were lower in the GH group. However, GH increased clinical pregnancy rate with significant difference. 4 IU-6 weeks GH pretreatment showed lowest duration of Gn and highest clinical pregnancy rate compared with other three groups. Number of transferred embryos was confounding factor both in univariate and multivariate analysis. Our study showed that co-treatment with GH in patients with normal ovarian response could increase pregnancy rate.


Assuntos
Gonadotropina Coriônica/administração & dosagem , Embrião de Mamíferos/citologia , Embrião de Mamíferos/efeitos dos fármacos , Hormônio do Crescimento/administração & dosagem , Infertilidade Feminina/tratamento farmacológico , Indução da Ovulação/métodos , Adulto , Estudos de Casos e Controles , Gonadotropina Coriônica/farmacologia , Quimioterapia Combinada , Transferência Embrionária/normas , Feminino , Fertilização In Vitro/métodos , Hormônio do Crescimento/farmacologia , Humanos , Recém-Nascido , Masculino , Gravidez , Taxa de Gravidez , Controle de Qualidade , Adulto Jovem
14.
Neuro Endocrinol Lett ; 39(7): 525-531, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30860684

RESUMO

OBJECTIVE: Growth hormone (GH) increases insulin-like growth factor I (IGF-I) production and both hormones affect hippocampal plasticity. We have previously shown that Hbb and Alas2 in the rat hippocampus were robustly regulated by GH-infusions for six days, whereas other transcripts were weakly affected. Here, we explored the effects of prolonged GH administration on transcripts linked to neuroprotection and investigated whether serum IGF-I administration may exert similar effects. DESIGN: Hypophysectomised female rats were infused with GH or IGF-I for 19 days. Hbb, Alas2 and seven additional GH- and IGF-I-related transcripts were quantified by Q-RT-PCR in rat hippocampus. RESULTS: Three transcripts, Hbb, Alas2, and Alox15 were increased by both GH and IGF-I administration. The other transcripts were marginally affected. CONCLUSION: The 19-day GH-infusion induced similar effects as those reported after 6-day GH treatment, with the addition of the regulation of transcript Alox15. IGF-I induced altered gene expression in relation to its effect on weight gain. This study underlines that there is an entity of transcripts involved in neuroprotection and vascular tone that is regulated by both systemic GH and IGF-I. For other transcripts, the longer duration of this study did not significantly enhance the marginal effects of GH administration seen previously.


Assuntos
Expressão Gênica/efeitos dos fármacos , Hormônio do Crescimento/farmacologia , Hipocampo/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , 5-Aminolevulinato Sintetase/biossíntese , Animais , Araquidonato 15-Lipoxigenase/biossíntese , Feminino , Hipofisectomia , Fator de Crescimento Insulin-Like I/metabolismo , Ratos , Ganho de Peso/efeitos dos fármacos , Globinas beta/biossíntese
15.
Nat Commun ; 10(1): 662, 2019 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-30737388

RESUMO

Weight loss triggers important metabolic responses to conserve energy, especially via the fall in leptin levels. Consequently, weight loss becomes increasingly difficult with weight regain commonly occurring in most dieters. Here we show that central growth hormone (GH) signaling also promotes neuroendocrine adaptations during food deprivation. GH activates agouti-related protein (AgRP) neurons and GH receptor (GHR) ablation in AgRP cells mitigates highly characteristic hypothalamic and metabolic adaptations induced by weight loss. Thus, the capacity of mice carrying an AgRP-specific GHR ablation to save energy during food deprivation is impaired, leading to increased fat loss. Additionally, administration of a clinically available GHR antagonist (pegvisomant) attenuates the fall of whole-body energy expenditure of food-deprived mice, similarly as seen by leptin treatment. Our findings indicate GH as a starvation signal that alerts the brain about energy deficiency, triggering key adaptive responses to conserve limited fuel stores.


Assuntos
Proteína Relacionada com Agouti/metabolismo , Receptores da Somatotropina/metabolismo , Proteína Relacionada com Agouti/genética , Animais , Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Metabolismo Energético/efeitos dos fármacos , Feminino , Hormônio do Crescimento/metabolismo , Hormônio do Crescimento/farmacologia , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/uso terapêutico , Leptina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores da Somatotropina/genética , Perda de Peso/efeitos dos fármacos
16.
Theriogenology ; 125: 331-334, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30504074

RESUMO

This study aimed to evaluate the effect of recombinant bovine somatotropin (bST) in combination with progesterone (P4) and estradiol benzoate (EB) on ovarian follicular dynamics using a protocol for estrus and ovulation synchronization in crossbred Bos taurus taurus cows. Twenty-four non-lactating multiparous cows were randomly assigned to two groups: the recombinant bovine somatotropin group (GbST; n = 11) received an intravaginal P4 device (1.5 g), estradiol benzoate (EB = 1.0 mg IM), bST (500 mg SC), and an ovarian ultrasonography (US) on day zero (d0 = beginning of the study); d-cloprostenol (150 µg, IM), US, and P4 removal on d8; 1.0 mg of EB (IM) on d9; and US on d10 and d15. On the other hand, to the control group (GC; n = 13), the same protocol as the GbST was applied, except for the non-receipt of bST on d0. The follicles were measured and evaluated on d0, d8, and d10, as were the corpora lutea (CL) on d15 (using ultrasonography). The effect of the two treatments (GbST vs. GC) on the follicle size, CL (F-test), and ovulation rate (logistic regression) were evaluated. The GbST showed a greater follicle diameter on d10 (14.5 mm) than the GC (12.1 mm; P < 0.03), as well as a greater diameter of CL on d15 (19.7 vs. 16.9 mm, P < 0.01). In addition, in the former, the ovulation rate (90.9 vs. 69.2%, P = 0.09) was observed to be greater. It was concluded that the combination of bST, P4, and EB in synchronization for estrus and ovulation protocols significantly increased the diameter of the preovulatory follicle, produced a higher follicular growth rate, and a greater diameter of the corpus luteum. Additionally, there was a higher percentage of cows with ovulation compared to the group that did not receive bST.


Assuntos
Bovinos , Estradiol/análogos & derivados , Sincronização do Estro/efeitos dos fármacos , Hormônio do Crescimento/farmacologia , Ovulação/efeitos dos fármacos , Progesterona/farmacologia , Animais , Estradiol/administração & dosagem , Estradiol/farmacologia , Feminino , Hormônio do Crescimento/administração & dosagem , Progesterona/administração & dosagem , Distribuição Aleatória
17.
Mol Cell Endocrinol ; 482: 28-36, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30543877

RESUMO

Cystatin C (CysC) is a marker for estimation of glomerular filtration rate (GFR). CysC levels may depend not only on clearance/GFR but possibly also on changes in production. Our studies on tissue distribution of CysC protein in mice showed that adipose tissue expresses significant amounts of CysC, suggesting that adipocytes could contribute to circulating CysC levels in vivo. As growth hormone (GH) and triiodothyronine (T3) increase both GFR and CysC (increased in acromegaly and hyperthyroidism) in vivo, we studied whether they could increase CysC production in 3T3-L1 adipocytes in vitro. CysC accumulated in culture media of 3T3-L1 adipocytes in a time-dependent fashion. GH and T3 both (10 nmol/l) increased accumulation of CysC, to 373 ±â€¯14 and 422 ±â€¯20, respectively, vs 298 ±â€¯10 ng per well over 4 days in controls. Thus, GH and T3 enhance the production of CysC by adipocytes in vitro.


Assuntos
Tecido Adiposo/metabolismo , Cistatina C/metabolismo , Hormônio do Crescimento/farmacologia , Tri-Iodotironina/farmacologia , Células 3T3-L1 , Tecido Adiposo/efeitos dos fármacos , Animais , Cistatina C/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Taxa de Filtração Glomerular/efeitos dos fármacos , Camundongos , Fatores de Tempo
18.
J Obstet Gynaecol Res ; 45(2): 376-381, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30276977

RESUMO

AIM: The purpose was to explore whether the 6 weeks of growth hormone (GH) pretreatment could increase the live birth rate of poor ovarian responders (POR). METHODS: This self-controlled, retrospective study was performed among 380 POR who had GH adjuvant (GH+) at a university-affiliated hospital in Guangzhou, China, from October 2010 to April 2016. Growth hormone was injected daily beginning with the previous menstruation and maintained until ovum pickup, for approximately 6 weeks. Clinical variables between the GH+ cycle and the other GH-free (GH-) cycle of each patient were compared. Both cycles were conducted with a similar conventional control ovarian hyperstimulation protocol for in vitro fertilization treatment. One to one case-control matching was performed to adjust essential confounding factors between GH+ cycles and GH- cycles. RESULTS: GH pretreatment improved embryo quality (1.14 ± 1.50 vs 0.11 ± 0.48, P < 0.05) and decreased miscarriage (18.8% vs 80.0%, P < 0.05) significantly, resulting in an increase in the live birth rate (23.5% vs 3.9%, P < 0.05). The oocyte utilization rate in GH+ cycles was remarkably improved, even with older patients and more failed previous attempts. Significant improvement in embryo quality was shown by an increased number of good-quality embryos and improved oocyte utilization rate after matching. CONCLUSIONS: The longer term use of low-dose GH administration for 6 weeks could be beneficial for the utilization of oocytes and for finally increasing the live birth rates of POR.


Assuntos
Fertilização In Vitro/métodos , Hormônio do Crescimento/farmacologia , Indução da Ovulação/métodos , Adulto , Feminino , Hormônio do Crescimento/administração & dosagem , Humanos , Estudos Retrospectivos
19.
Theriogenology ; 123: 159-166, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30308392

RESUMO

This study used a comparative approach to gather clinical information to assess the effect of bovine somatotropin (bST) on follicular dynamics and ovulation in sheep and goats during an interovulatory cycle. The performance of general markers of ovarian function and specific features of follicular dynamics obtained by daily ultrasonography (US) were used to assess the hypothesis that bST, associated with supraphysiological levels of IGF-I, was able to disrupt the follicular dynamics and ovulation in Highlander ewes and Saanen goats. In Exp 1, 15 ewes and 14 goats were estrous-synchronized (P4-6 days + PGFα d-6) and then allocated to a bST-treated group (50 and 100 mg, Lactotropin®; n = 5 females each) and to an untreated control group (5 ewes and 4 goats) to assess the activity of bST through plasma IGF-I (RIA). In Exp 2, 12 animals from each species were synchronized. At day 6, they were divided into a bST-group (100 mg in sheep and 50 mg in goats, n = 6 each) and an untreated control group (n = 6 each). Starting at day 6 and up to 22 days after ovulation in sheep and 25 days in goats, each female was subjected to daily US (10 mHz probe) to assess follicular and luteal (CL) dynamics and ovulation. This included assessments of both general ovarian features and specific follicular wave features. Our results showed that bST increased plasma IGF-I by day 3 (p < 0.01) when compared to the control group. Moreover, these concentrations were maintained for at least 10 days in sheep and 10 days in goats before returning to pre-treatment concentrations. Increases in IGF-I after bST doses were similar in terms of a daily and total amount (P > 0.10). Results from Exp.2 indicate that in sheep, bST administration had a subtle inhibitory effect on follicular function. However, bST in goats had a stronger influence, extending the interovulatory cycle (P = 0,034), increasing the number of follicular waves during the period (P = 0.003), and reducing the functional potential of large follicles as measured by their lower follicular diameter (P = 0.02), duration of the follicle waves (P = 0.02), and persistence of follicles after reaching their maximum diameters (P = 0.04). In addition, untreated sheep and goats shared common patterns of terminal follicular development and ovulations characterized by overlapping between follicular waves and ovulations of follicles from different waves, features not seen in cattle.


Assuntos
Cabras/fisiologia , Hormônio do Crescimento/farmacologia , Fator de Crescimento Insulin-Like I/metabolismo , Folículo Ovariano/efeitos dos fármacos , Ovulação/efeitos dos fármacos , Ovinos/fisiologia , Animais , Ciclo Estral , Sincronização do Estro , Feminino
20.
Nature ; 564(7736): 415-419, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30546139

RESUMO

We previously reported1 the presence of amyloid-ß protein (Aß) deposits in individuals with Creutzfeldt-Jakob disease (CJD) who had been treated during childhood with human cadaveric pituitary-derived growth hormone (c-hGH) contaminated with prions. The marked deposition of parenchymal and vascular Aß in these relatively young individuals with treatment-induced (iatrogenic) CJD (iCJD), in contrast to other prion-disease patients and population controls, allied with the ability of Alzheimer's disease brain homogenates to seed Aß deposition in laboratory animals, led us to argue that the implicated c-hGH batches might have been contaminated with Aß seeds as well as with prions. However, this was necessarily an association, and not an experimental, study in humans and causality could not be concluded. Given the public health importance of our hypothesis, we proceeded to identify and biochemically analyse archived vials of c-hGH. Here we show that certain c-hGH batches to which patients with iCJD and Aß pathology were exposed have substantial levels of Aß40, Aß42 and tau proteins, and that this material can seed the formation of Aß plaques and cerebral Aß-amyloid angiopathy in intracerebrally inoculated mice expressing a mutant, humanized amyloid precursor protein. These results confirm the presence of Aß seeds in archived c-hGH vials and are consistent with the hypothesized iatrogenic human transmission of Aß pathology. This experimental confirmation has implications for both the prevention and the treatment of Alzheimer's disease, and should prompt a review of the risk of iatrogenic transmission of Aß seeds by medical and surgical procedures long recognized to pose a risk of accidental prion transmission2,3.


Assuntos
Doença de Alzheimer/induzido quimicamente , Peptídeos beta-Amiloides/metabolismo , Cadáver , Síndrome de Creutzfeldt-Jakob/induzido quimicamente , Contaminação de Medicamentos , Hormônio do Crescimento/farmacologia , Doença Iatrogênica , Doença de Alzheimer/etiologia , Peptídeos beta-Amiloides/análise , Precursor de Proteína beta-Amiloide/administração & dosagem , Precursor de Proteína beta-Amiloide/efeitos adversos , Animais , Estudos de Casos e Controles , Síndrome de Creutzfeldt-Jakob/etiologia , Modelos Animais de Doenças , Transmissão de Doença Infecciosa/prevenção & controle , Transmissão de Doença Infecciosa/estatística & dados numéricos , Contaminação de Medicamentos/prevenção & controle , Contaminação de Medicamentos/estatística & dados numéricos , Feminino , Hormônio do Crescimento/administração & dosagem , Humanos , Masculino , Camundongos , Modelos Biológicos , Príons/metabolismo , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Reprodutibilidade dos Testes , Proteínas tau/análise , Proteínas tau/metabolismo
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