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1.
J Endocrinol ; 245(2): 327-342, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32176867

RESUMO

Circulating growth hormone (GH) concentrations increase during pregnancy in mice and remain pituitary-derived. Whether abundance or activation of the GH secretagogue ghrelin increase during pregnancy, or in response to dietary octanoic acid supplementation, is unclear. We therefore measured circulating GH profiles in late pregnant C57BL/6J mice and in aged-matched non-pregnant females fed with standard laboratory chow supplemented with 5% octanoic or palmitic (control) acid (n = 4-13/group). Serum total and acyl-ghrelin concentrations, stomach and placenta ghrelin mRNA and protein expression, Pcsk1 (encoding prohormone convertase 1/3) and Mboat4 (membrane bound O-acyl transferase 4) mRNA were determined at zeitgeber (ZT) 13 and ZT23. Total and basal GH secretion were higher in late pregnant than non-pregnant mice (P < 0.001), regardless of diet. At ZT13, serum concentrations of total ghrelin (P = 0.004), but not acyl-ghrelin, and the density of ghrelin-positive cells in the gastric antrum (P = 0.019) were higher, and gastric Mboat4 and Pcsk1 mRNA expression were lower in pregnant than non-pregnant mice at ZT23. In the placenta, ghrelin protein was localised mostly to labyrinthine trophoblast cells. Serum acyl-, but not total, ghrelin was lower at mid-pregnancy than in non-pregnant mice, but not different at early or late pregnancy. In conclusion, dietary supplementation with 5% octanoic acid did not increase activation of ghrelin in female mice. Our results further suggest that increases in maternal GH secretion throughout murine pregnancy are not due to circulating acyl-ghrelin acting at the pituitary. Nevertheless, time-dependent increased circulating total ghrelin could potentially increase ghrelin action in tissues that express the acylating enzyme and receptor.


Assuntos
Caprilatos/farmacologia , Suplementos Nutricionais , Grelina/efeitos dos fármacos , Hormônio do Crescimento/efeitos dos fármacos , Acilação , Animais , Feminino , Mucosa Gástrica/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Placenta/metabolismo , Gravidez , RNA Mensageiro/metabolismo
2.
J Dairy Sci ; 100(7): 5888-5898, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28456404

RESUMO

The objective of the study was to evaluate the effect of prepartum and postpartum (PP) supplementation with 2 isomers of conjugated linoleic acid (CLA) on reproductive parameters and some related metabolic factors in dairy cows. High-producing, multiparous Holstein Friesian cows (n = 60) were allotted to 3 treatment groups: the CLA1 group (n = 20) was supplemented with 70 g of lipid-encapsulated CLA providing 7 g each of cis-9,trans-11 and trans-10,cis-12 CLA from d 21 (d 21) before expected calving until d 7 after artificial insemination (AI), that is, until 77 to 91 d PP; the CLA2 group (n = 20) was supplemented with the same amount of CLA beginning at calving until d 7 after AI; and the control group (n = 20) received an isocaloric, isonitrogenous, and isolipidic diet. Blood samples were taken weekly to measure glucose, insulin, insulin-like growth factor-I (IGF-I), and leptin. Liver biopsy was performed in 10 cows per group for growth hormone receptor 1A and IGF-I mRNA analyses. At d 49 to 63 PP, ovulation was synchronized with the Pre-Synch protocol followed by fixed-time AI. Milk progesterone was monitored from calving until d 35 post-AI. Cows returning to estrus following AI were inseminated. Supplementation with CLA before calving improved the recovery of plasma leptin levels in the early PP period (from the day of calving until wk 3 PP; treatment effect). Later PP (wk 5), plasma IGF-I, and leptin remained significantly higher in both CLA1 and CLA2 groups compared with control, although hepatocellular IGF-I mRNA was not different among groups. Plasma IGF-I levels remained higher in both CLA-treated groups on the day of AI. Growth hormone receptor 1A mRNA levels in hepatic tissue decreased in all groups, reaching a nadir in the first week PP. Days to first PP ovulation did not differ between groups; however, both supplemented groups conceived earlier compared with control (d 97 ± 19, d 97 ± 23, and d 113 ± 30 for CLA1, CLA2, and control, respectively). Plasma progesterone concentration was higher in both supplemented groups on d 2 to 5 following the synchronized ovulation than in controls. We concluded that CLA supplementation around calving alters PP metabolic signals as reflected by higher plasma leptin and IGF-I levels. Conjugated linoleic acid stimulated early luteal function and reduced the PP interval to conception.


Assuntos
Bovinos , Hormônio do Crescimento/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Ácidos Linoleicos Conjugados/administração & dosagem , Reprodução/efeitos dos fármacos , Animais , Feminino , Lactação , Lipídeos , Leite , Período Pós-Parto , Gravidez
3.
Animal ; 11(11): 1905-1912, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28318464

RESUMO

Many fibre sources can help the adaptation of piglets at weaning, improving the growth. In this study, the effects of a dietary crude fibre concentrate (CFC) on piglet's growth was investigated. From 31 to 51 days of age, 108 weaned piglets (D×(Lw×L)), had access to two isofibrous, isoenergetic and isonitrogenous diets, supplemented with 1% of CFC (CFC group) or not (control (CON) group). From days 52 to 64 all piglets received the same starter diet. During the dietary treatment period the CFC group showed higher average daily gain, average daily feed intake and feed efficiency (P<0.001) than CON group. At 64 days of age, BW was higher in CFC group compared with CON group (P<0.001). Blood samples were collected at days 31, 38, 45 and 52 of age. From days 31 to 52 significant differences in the somatotropic axis between groups were observed. In particular, growth hormone levels were higher only at the end of the 1st week of dietary treatment (P<0.05) in CFC group animals compared with CON group animals. The IGF-I trend was similar between groups even if the IGF-I levels were higher in the CFC group than CON group 1 week after starting treatment (P<0.01). The IGF-binding protein 3 (IGFBP-3) levels were higher in the first 2 weeks of dietary treatment and lower in the 3rd week in CON group compared with CFC group (P<0.01). Specifically, the IGFBP-3 profile was consistent with that of IGF-I in CFC group but not in CON group. At the same time, an increase of leptin in CFC compared with CON group was observed (P<0.05). Piglets fed the CFC diet showed a lower diarrhoea incidence (P<0.05) and a lower number of antibiotic interventions (P<0.05) than CON diet from 31 to 51 days of age. Pig-major acute-phase protein plasma level (P<0.01) and interleukin-6 gene expression (P<0.05) were higher in CON group than CFC group at the end of 1st week of dietary treatment. In conclusion, this study showed that CFC diet influences the hormones related to energy balance enhancing the welfare and growth of piglets. Furthermore, the increase in feed intake during 3 weeks of dietary treatment improved the feed efficiency over the entire post-weaning period.


Assuntos
Fibras na Dieta/farmacologia , Suplementos Nutricionais , Hormônio do Crescimento/efeitos dos fármacos , Suínos/crescimento & desenvolvimento , Ração Animal , Animais , Dieta/veterinária , Feminino , Hormônio do Crescimento/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Masculino , Suínos/fisiologia , Desmame , Aumento de Peso/efeitos dos fármacos
4.
J Anim Sci ; 93(3): 1052-60, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26020882

RESUMO

This study investigated the effects of various standardized ileal digestible (SID) Trp to Lys ratios on the performance and carcass characteristics of late finishing gilts receiving low-CP (9.6%) diets supplemented with crystalline AA. Ninety gilts (89.1 ± 5.1 kg) were used in a dose-response study conducted for 35 d. Crystalline Trp (0, 0.1, 0.2, 0.4, or 0.6 g/kg) was added to a corn-wheat bran basal diet providing SID Trp to Lys ratios of 0.12, 0.15, 0.18, 0.21, or 0.24. Each diet was fed to 6 pens of pigs with 3 gilts per pen. At the end of the experiment, 30 gilts (1 pig per pen) were slaughtered to evaluate carcass traits and meat quality (BW = 121 kg). Increasing the SID Trp to Lys ratio increased ADG (linear and quadratic effect, < 0.05) and also improved G:F (linear and quadratic effect, < 0.05). Serum urea nitrogen (SUN) decreased as the SID Trp to Lys ratio increased (linear and quadratic effects, < 0.05). A quadratic effect of L* light and marbling in the longissimus dorsi was observed as the dietary SID Trp to Lys ratio increased ( < 0.05). Increasing the SID Trp to Lys ratio increased the level of serum GH (quadratic effect, < 0.05) and also increased the level of serum IGF-1 (linear and quadratic effect, < 0.05). Increasing the SID Trp to Lys ratio increased the protein abundance of the muscular AA transporter of sodium-coupled neutral amino acid transporter 2 (SNAT2) in the longissimus dorsi muscle (linear and quadratic effect, < 0.05). The optimum SID Trp to Lys ratios to maximize ADG and G:F as well as to minimize SUN levels were 0.16, 0.17, and 0.16 using a linear-breakpoint model and 0.20, 0.20, and 0.20 using a quadratic model. Tryptophan could influence serum GH and IGF-1 secretion and protein abundance of the muscular AA transporter of SNAT2 in the longissimus dorsi muscle in late finishing gilts fed low-protein diets.


Assuntos
Dieta com Restrição de Proteínas/veterinária , Íleo/metabolismo , Lisina/farmacologia , Suínos/crescimento & desenvolvimento , Triptofano/farmacologia , Sistemas de Transporte de Aminoácidos/efeitos dos fármacos , Sistemas de Transporte de Aminoácidos/metabolismo , Ração Animal/análise , Criação de Animais Domésticos/métodos , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Animal/fisiologia , Animais , Nitrogênio da Ureia Sanguínea , Dieta com Restrição de Proteínas/normas , Suplementos Nutricionais/normas , Feminino , Hormônio do Crescimento/sangue , Hormônio do Crescimento/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/metabolismo , Lisina/análise , Lisina/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Suínos/metabolismo , Triptofano/análise , Triptofano/metabolismo
5.
Lancet Diabetes Endocrinol ; 3(7): 568-76, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25873572

RESUMO

The past 30 years have seen a great improvement in survival of children and young adults treated for cancer. Cancer treatment can put patients at risk of health problems that can develop many years later, most commonly affecting the endocrine system. Patients treated with cranial radiotherapy often develop dysfunction of the hypothalamic-pituitary axis. A characteristic pattern of hormone deficiencies develops over several years. Growth hormone is disrupted most often, followed by gonadal, adrenal, and thyroid hormones, leading to abnormal growth and puberty in children, and affecting general wellbeing and fertility in adults. The severity and rate of development of hypopituitarism is determined by the dose of radiotherapy delivered to the hypothalamic-pituitary axis. Individual growth hormone deficiencies can develop after a dose as low as 10 Gy, whereas multiple hormone deficiencies are common after 60 Gy. New techniques in radiotherapy aim to reduce the effect on the hypothalamic-pituitary axis by minimising the dose received. Patients taking cytotoxic drugs do not often develop overt hypopituitarism, although the effect of radiotherapy might be enhanced. The exception is adrenal insufficiency caused by glucocorticosteroids which, although transient, can be life-threatening. New biological drugs to treat cancer can cause autoimmune hypophysitis and hypopituitarism; therefore, oncologists and endocrinologists should be vigilant and work together to optimise patient outcomes.


Assuntos
Neoplasias Encefálicas/radioterapia , Doenças do Sistema Endócrino/etiologia , Hipotálamo/efeitos da radiação , Hipófise/efeitos da radiação , Adolescente , Antineoplásicos/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Criança , Doenças do Sistema Endócrino/fisiopatologia , Hormônio do Crescimento/deficiência , Hormônio do Crescimento/efeitos dos fármacos , Hormônio do Crescimento/efeitos da radiação , Humanos , Hipotálamo/efeitos dos fármacos , Hipotálamo/fisiopatologia , Masculino , Hipófise/efeitos dos fármacos , Hipófise/fisiopatologia , Radioterapia/efeitos adversos , Fatores de Risco
6.
J Strength Cond Res ; 24(4): 1082-90, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20300016

RESUMO

This placebo-controlled double-blind study was designed to investigate the effect of arginine and ornithine (arg and orn) supplementation during 3-week heavy-resistance training on serum growth hormone/insulin-like growth factor-1/insulin-like growth factor-binding protein 3 (GH/IGF-1/IGFBP-3), testosterone, cortisol, and insulin levels in experienced strength-trained athletes. The subjects were randomly divided between a placebo group (n = 8) and the l-Arg/l-Orn-supplemented group (n = 9), and performed pre and posttraining standard exercise tests with the same absolute load, which consisted of the same exercise schedule as that applied in the training process. Fasting blood samples were obtained at rest, 2 minutes after the cessation of the strength exercise protocol, and after 1 hour of recovery. The resting concentrations of the investigated hormones and IGFBP-3 did not differ significantly between the study groups. In response to exercise test, all the hormones were elevated (p < 0.05) at both time points. Significant increases (p < 0.05) were observed in both GH and IGF-1 serum levels after arg and orn supplementation at both time points, whereas a significant decrease was seen in IGFBP-3 protein during the recovery period. Because there was no between-group difference in the remaining hormone levels, it appears that the GH/IGF-1/IGFBP-3 complex may be the major player in muscle tissue response to short-term resistance training after arg and orn supplementation.


Assuntos
Arginina/administração & dosagem , Suplementos Nutricionais , Hormônio do Crescimento/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Ornitina/administração & dosagem , Treinamento Resistido/métodos , Administração Oral , Análise de Variância , Antropometria , Atletas , Desempenho Atlético , Índice de Massa Corporal , Método Duplo-Cego , Hormônio do Crescimento/efeitos dos fármacos , Humanos , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Masculino , Força Muscular/efeitos dos fármacos , Força Muscular/fisiologia , Resistência Física/efeitos dos fármacos , Resistência Física/fisiologia , Adulto Jovem
7.
J Pharmacol Sci ; 104(4): 319-28, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17666866

RESUMO

N(omega)-Nitro-L-arginine methyl ester (L-NAME) induces a pre-eclampsia-like syndrome in pregnant rats. We have previously reported the anti-hypertensive effects of several Japanese traditional (Kampo) medicines in this model, and one of these, Tokishakuyakusan (TS), also improved intrauterine growth retardation (IUGR). In the present study, we characterized the effect of TS on IUGR. TS administration reversed the decrease in fetal body weight and fetal blood glucose concentration induced by the infusion of L-NAME. Growth hormone (GH) levels in the fetal blood, which were decreased by L-NAME infusion, were also significantly elevated by TS; however, levels of GH releasing hormone (GHRH) and insulin-like growth factor I (IGF-I) were unchanged and only slightly changed, respectively. Treatment with L-NAME with or without TS had no apparent effect on GH, GHRH, and IGF-I levels of dams. In an immunocytochemical study, the number of GH-positive cells in the fetal pituitary gland was significantly increased in TS-treated rats. These data suggest that enhanced proliferation of somatotrope cells of the pituitary gland and the resultant increase in GH secretion in the fetus may be involved in the improvement of IUGR by TS.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Retardo do Crescimento Fetal/tratamento farmacológico , Pré-Eclâmpsia/tratamento farmacológico , Animais , Glicemia/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Peso Fetal/efeitos dos fármacos , Hormônio do Crescimento/efeitos dos fármacos , Hormônio Liberador de Hormônio do Crescimento/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Masculino , NG-Nitroarginina Metil Éster , Hipófise/citologia , Hipófise/efeitos dos fármacos , Placenta/efeitos dos fármacos , Placentação , Plantas Medicinais/química , Pré-Eclâmpsia/induzido quimicamente , Gravidez , Ratos , Ratos Sprague-Dawley
8.
Eur J Pediatr ; 165(9): 618-24, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16703326

RESUMO

BACKGROUND: The aim of this study was to investigate the effects of arginine on nutrition, growth and urea cycle function in boys with late-onset ornithine transcarbamylase deficiency (OTCD). Seven Japanese boys with late-onset OTCD enrolled in this study resumed arginine treatment after the cessation of this therapy for a few years. Clinical presentations such as vomiting and unconsciousness, plasma amino acids and urinary orotate excretion were followed chronologically to evaluate urea cycle function and protein synthesis with and without this therapy. In addition to height and body weight, blood levels of proteins, lipids, growth hormone (GH), insulin-like growth factor-I (IGF-I) and IGF-binding protein -3 (IGFBP-3) were monitored. RESULTS: The frequency of hyperammonemic attacks and urinary orotate excretion decreased significantly following the resumption of arginine treatment. Despite showing no marked change in body weight, height increased gradually. Extremely low plasma arginine increased to normal levels, while plasma glutamine and alanine levels decreased considerably. Except for a slight increase in high-density lipoprotein cholesterol level, blood levels of markers for nutrition did not change. In contrast, low serum IGF-I and IGFBP-3 levels increased to age-matched control levels, and normal urinary GH secretion became greater than the level observed in the controls. CONCLUSION: Arginine treatment is able to reduces attacks of hyperammonemia in boys with late-onset OTCD and to increase their growth.


Assuntos
Arginina/uso terapêutico , Crescimento/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição/efeitos dos fármacos , Doença da Deficiência de Ornitina Carbomoiltransferase/tratamento farmacológico , Doença da Deficiência de Ornitina Carbomoiltransferase/fisiopatologia , Ureia/metabolismo , Idade de Início , Aminoácidos/sangue , Aminoácidos/efeitos dos fármacos , Amônia/sangue , Análise de Variância , Arginina/sangue , Biomarcadores/sangue , Biomarcadores/urina , Proteínas Sanguíneas/efeitos dos fármacos , Proteínas Sanguíneas/metabolismo , Estatura/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Pré-Escolar , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dieta com Restrição de Proteínas , Hormônio do Crescimento/sangue , Hormônio do Crescimento/efeitos dos fármacos , Hormônio do Crescimento/urina , Humanos , Hiperamonemia/dietoterapia , Hiperamonemia/tratamento farmacológico , Hiperamonemia/etiologia , Hiperamonemia/metabolismo , Hiperamonemia/fisiopatologia , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/metabolismo , Japão , Masculino , Doença da Deficiência de Ornitina Carbomoiltransferase/complicações , Doença da Deficiência de Ornitina Carbomoiltransferase/dietoterapia , Doença da Deficiência de Ornitina Carbomoiltransferase/metabolismo , Ácido Orótico/urina , Tireotropina/sangue , Fatores de Tempo , Resultado do Tratamento , Triglicerídeos/sangue
9.
Neuroendocrinology ; 77(6): 380-7, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12845224

RESUMO

Testosterone (T) is known to affect the growth hormone (GH) axis. However, the mechanisms underlying the activation of GH secretion by T still remain to be clarified. Available data in animals and humans have shown that withdrawal of somatostatin (SRIH) infusion induces a GH-releasing hormone (GHRH)-mediated rebound release of GH, and there is accumulating evidence that SRIH infusion withdrawal may be a useful test to probe the GHRH function in vivo. With the aim of investigating whether the stimulatory effect of androgens on GH release in man could be accounted for by activation of the hypothalamic GHRH tone, we evaluated the plasma GH response to SRIH withdrawal in 10 patients aged 29.6 +/- 2.4 years (mean +/- SEM), diagnosed with hypergonadotropic hypogonadism, before and after a 6-month replacement therapy with T enanthate (250 mg every 3 weeks, i.m.), and in 10 healthy men, aged 26.7 +/- 2.8 years. To verify whether the modulation of GH secretion by T could also be mediated through changes in SRIH tone and/or pituitary releasable pool, we examined GH secretory responses to combined GHRH and L-arginine (ARG) in the same individuals. Basal plasma concentrations of GH (0.48 +/- 0.11 microg/l) and IGF-I (23.79 +/- 1.83 nmol/l) were significantly lower in untreated hypogonadal patients than in healthy men, and significantly increased after T replacement therapy (GH 1.13 +/- 0.28 microg/l; IGF-I 28.71 +/- 1.46 nmol/l). The mean Delta GH peak after SRIH withdrawal recorded in untreated hypogonadal men (2.65 +/- 0.86 microg/l) was significantly (p < 0.05) lower than that observed in healthy men (6.53 +/- 1.33 microg/l) and significantly increased after T replacement therapy (5.52 +/- 1.25 microg/l). The GH responses to GHRH combined with ARG (a functional SRIH antagonist) were not significantly different between healthy men and untreated hypogonadal patients, and were not significantly affected by T treatment. Plasma T and estradiol (E(2)) levels significantly correlated with Delta GH peak after SRIH withdrawal in healthy men and in T-treated hypogonadal patients, whereas in untreated patients they did not. No significant correlation was found between GH areas under the curve after GHRH + ARG test and T and E(2) plasma levels in either healthy men or in hypogonadal patients (both before and after T replacement). These findings are consistent with the view that in humans the stimulatory action of T on the GH axis appears to be mediated at the hypothalamic level primarily by promoting GHRH function.


Assuntos
Hormônio Liberador de Hormônio do Crescimento/metabolismo , Hormônio do Crescimento/metabolismo , Hipogonadismo/metabolismo , Hipotálamo/metabolismo , Hipófise/metabolismo , Testosterona/administração & dosagem , Testosterona/metabolismo , Adulto , Área Sob a Curva , Arginina/administração & dosagem , Arginina/metabolismo , Estudos de Casos e Controles , Estradiol/sangue , Hormônio do Crescimento/sangue , Hormônio do Crescimento/efeitos dos fármacos , Hormônio Liberador de Hormônio do Crescimento/administração & dosagem , Hormônio Liberador de Hormônio do Crescimento/efeitos dos fármacos , Heptanoatos/administração & dosagem , Heptanoatos/metabolismo , Humanos , Hipogonadismo/tratamento farmacológico , Hipotálamo/efeitos dos fármacos , Ensaio Imunorradiométrico , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Hipófise/efeitos dos fármacos , Radioimunoensaio , Somatostatina/metabolismo
10.
J Strength Cond Res ; 16(2): 179-83, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-11991768

RESUMO

Ginseng, an herbal plant, has been ingested by many athletes in Oriental regions of the world in order to improve stamina and to facilitate rapid recovery from injuries. However, adequate investigation has not been conducted to examine the ergogenic effects of ginseng. To examine the effects of ginseng supplements on hormonal status following acute resistance exercise, eight male college students were randomly given water (control; CON) or 20 g of ginseng root extract (GIN) treatment immediately after a standardized exercise bout. Venous blood samples were drawn before and immediately after exercise and at 4 time points during a 2-hour recovery period. Human growth hormone, testosterone, cortisol, and insulin-like growth factor 1 (IGF-1) levels were determined by radioimmunoassay. The responses of plasma hormones following ginseng consumption were not significant between CON and GIN treatments during the 2-hour recovery period. These results do not support the use of ginseng to promote an anabolic hormonal status following resistance exercise.


Assuntos
Hormônio do Crescimento/efeitos dos fármacos , Hidrocortisona/sangue , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Panax , Fitoterapia , Testosterona/sangue , Administração Oral , Adulto , Exercício Físico/fisiologia , Hormônio do Crescimento/sangue , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Ácido Láctico/sangue , Masculino , Extratos Vegetais/administração & dosagem , Biossíntese de Proteínas , Proteínas/efeitos dos fármacos , Levantamento de Peso/fisiologia
11.
Bioorg Med Chem ; 10(6): 2023-9, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11937362

RESUMO

Previous studies from this laboratory demonstrated that N-methylation at Lys(5) residue in somatostatin octapeptide antagonist analogues increased the GH release inhibition potency by as much as 300%. We have now further investigated N-methylation of this Lys(5) residue in conjunction with a number of N- and C-terminal modifications previously found to give highly potent somatostatin receptor antagonists. Synthetic analogues were tested in a functional assay for their ability to inhibit somatostatin-inhibited GH release from rat pituitary cells in culture and to displace 125I-labeled somatostatin from CHO cells transfected with the five known human somatostatin receptors. Several interesting observations resulted from the study. Replacement of liphophilic Nal(8) at the C-terminus with a hydrophilic His(8) resulted in the increased affinity and selectivity for type 2 receptor to give the most potent antagonist analogue yet discovered (K(i), 1.5 nM), although in the rat pituitary cells inhibitory activity on somatostatin inhibited GH release decreased somewhat. A His(3) substitution within the cyclic portion of the analogues retained pituitary cell potency and affinity for type 2 receptor as did substitution with Bip(8) and Fpa(1). Replacement of Cpa(1) with Iph(1) did not effect the affinity for type 2 receptor significantly, but did decrease the effects on rat cell GH release. Iph(3) within-ring substitution increased the selectivity for sst(2) appreciably although the affinity for that receptor was considerably decreased. Substitution of Npa(3) resulted in good selectivity for sst(2) receptor. Replacement of Nal(8) with D-Trp(8) also increased the selectivity for type 2 receptor. Use of a 'bivalent ligand' approach in which two peptides were joined by 4,4'-biphenyldicarbonyl as a spacer destroyed the affinity for all the subtypes, however, the bivalent ligand formed with the Ahp spacer displayed significant affinity and high selectivity for the type 2 receptor.


Assuntos
Avaliação Pré-Clínica de Medicamentos , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Somatostatina/antagonistas & inibidores , Motivos de Aminoácidos , Sequência de Aminoácidos , Animais , Células CHO , Células Cultivadas , Clonagem Molecular , Cricetinae , Hormônio do Crescimento/efeitos dos fármacos , Hormônio do Crescimento/metabolismo , Humanos , Masculino , Espectrometria de Massas , Metilação , Oligopeptídeos/síntese química , Hipófise/citologia , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Ensaio Radioligante , Ratos , Receptores de Somatostatina/antagonistas & inibidores , Receptores de Somatostatina/genética , Receptores de Somatostatina/metabolismo , Transfecção
12.
Br J Pharmacol ; 134(4): 887-95, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11606330

RESUMO

1. This study exploited established immunoneutralization protocols and an N-terminal annexin 1 peptide (annexin 1(Ac2 - 26)) to advance our knowledge of the role of annexin 1 as a mediator of acute glucocorticoid action in the rat neuroendocrine system in vivo. 2. Rats were treated with corticosterone (500 microg kg(-1), i.p.) or annexin 1(Ac2 - 26) (0.1 - 10 ng rat(-1), i.c.v.) and 75 min later with interleukin 1beta (IL-1beta, 10 ng rat(-1), i.c.v. or 500 microg kg(-1), i.p). Blood was collected 1 h later for hormone immunoassay. Where appropriate, anti-annexin 1 polyclonal antiserum (pAb) was administered subcutaneously or centrally prior to the steroid challenge. 3. Corticosterone did not affect the resting plasma corticotrophin (ACTH) concentration but suppressed the hypersecretion of ACTH induced by IL-1beta (i.p. or i.c.v.). Its actions were quenched by anti-annexin 1 pAb (s.c. or i.c.v) and mimicked by annexin 1(Ac2 - 26). 4. By contrast, corticosterone provoked an increase in serum growth hormone (GH) which was ablated by central but not peripheral administration of anti-annexin 1 pAb. IL-1beta (i.c.v. or i.p.) did not affect basal GH but, when given centrally but not peripherally, it abolished the corticosterone-induced hypersecretion of GH. Annexin 1(Ac2 - 26) (i.c.v.) also produced an increase in serum GH which was prevented by central injection of IL-1beta. 5. The results support the hypothesis that the acute regulatory actions of glucocorticoids on hypothalamo-pituitary-adrenocortical function require annexin 1. They also provide novel evidence that the positive influence of the steroids on GH secretion evident within this timeframe is effected centrally via an annexin 1-dependent mechanism which is antagonized by IL-1beta.


Assuntos
Hormônio Adrenocorticotrópico/efeitos dos fármacos , Glucocorticoides/farmacologia , Hormônio do Crescimento/efeitos dos fármacos , Interleucina-1/farmacologia , Hormônio Adrenocorticotrópico/sangue , Hormônio Adrenocorticotrópico/metabolismo , Animais , Anexina A1/imunologia , Anexina A1/farmacologia , Anexina A1/fisiologia , Anticorpos Monoclonais/farmacologia , Corticosterona/farmacologia , Hormônio do Crescimento/sangue , Hormônio do Crescimento/metabolismo , Hipotálamo/metabolismo , Soros Imunes/farmacologia , Injeções Intraperitoneais , Injeções Intraventriculares , Hormônio Luteinizante/sangue , Hormônio Luteinizante/efeitos dos fármacos , Masculino , Peptídeos , Ratos , Ratos Sprague-Dawley
14.
Eur J Med Chem ; 35(6): 599-618, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10906412

RESUMO

Based on NN703, low molecular weight growth hormone secretagouges (GHSs) with a reduced number of hydrogen binding sites were designed by removal of the C-terminal amide group. The compounds were highly potent in combination with high efficacy in a rat pituitary cell assay, being characterized with EC(50) values down to 0.8 nM. Selected compounds were tested in in vivo animal models. The oral bioavailability in dogs was 16-44%. Also, the ED(50) values of the compounds were determined both in dog and swine.


Assuntos
Dipeptídeos/química , Dipeptídeos/farmacologia , Hormônio do Crescimento/metabolismo , Tiofenos/química , Tiofenos/farmacologia , Administração Oral , Animais , Sítios de Ligação , Disponibilidade Biológica , Cães , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Hormônio do Crescimento/efeitos dos fármacos , Hidrogênio , Masculino , Mimetismo Molecular , Peso Molecular , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Ratos , Relação Estrutura-Atividade , Sulfonamidas/química , Sulfonamidas/farmacologia , Suínos
15.
J Nutr ; 130(2): 158-63, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10720163

RESUMO

Zinc is thought to be an integral part of nuclear receptor proteins, stabilizing them in a conformation required for binding to target genes. However, we have recently shown that restriction of zinc availability with a chelator (diethylenetriaminepenta-acetic acid, DTPA) enhances, rather than inhibits, the ability of thyroid hormone to induce growth hormone mRNA expression in GH3 rat pituitary tumor cells. In this report, we have extended these observations by showing that a prolonged (48 h) exposure to DTPA is required to see these effects. The induction by DTPA can be reversed by subsequent addition of zinc, but again, this reversal is slow. A second chelator, EDTA, can also induce growth hormone gene expression in the presence of thyroid hormone, though it is less potent than DTPA. Other agents which act via the nuclear receptor pathway, all-trans and 9-cis retinoic acid, also induce expression of growth hormone mRNA. Addition of DTPA amplifies these effects in a zinc-dependent manner. Thus chelation of zinc potentiates the action of ligands acting via nuclear receptors on growth hormone gene expression. The delayed nature of the response suggests an indirect effect.


Assuntos
Quelantes/uso terapêutico , Ácido Edético/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Hormônio do Crescimento/efeitos dos fármacos , Hormônio do Crescimento/genética , Neoplasias Hipofisárias/metabolismo , Receptores Citoplasmáticos e Nucleares/efeitos dos fármacos , Tri-Iodotironina/farmacologia , Zinco/farmacologia , Análise de Variância , Animais , Antineoplásicos/uso terapêutico , Northern Blotting , Interações Medicamentosas , Ácido Pentético/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos , Tretinoína/uso terapêutico , Células Tumorais Cultivadas
16.
Pharmacol Res ; 36(1): 49-54, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9368914

RESUMO

The growth hormone-releasing peptide Hexarelin (Hexa; 80 micrograms/kg-1, s.c.) was administered for 30 and 60 days to old rats. The GH-releasing effect of Hexa was maintained during chronic treatment. At the end of the treatment, old rats were administered once with Hexa which elicited a greater GH response in rats chronically treated with the peptide than in those receiving a placebo. Pituitary GHmRNA concentrations were significantly lower in the older rats than in the younger animals, irrespective of Hexa treatment, while the GH protein content was similar in all the groups studied. The same was true for hypothalamic GHRH, whose synthesis was reduced in all the older animals but not in the young, in the presence of maintained concentrations of the peptide. Somatostatin mRNA concentrations were significantly higher in the hypothalami of older rats and administration of Hexa for 30 or 60 days brought the concentrations of somatostatin mRNA of aged rats to 'young' levels. Treatments with Hexa failed to alter the circulating levels of IGF-1. The data reported in this article indicate that long-term treatment with Hexa normalized some biological indices of somatotrophic function in aged rats.


Assuntos
Envelhecimento/fisiologia , Hormônio do Crescimento/efeitos dos fármacos , Hormônio do Crescimento/metabolismo , Oligopeptídeos/farmacologia , Animais , Hormônio Liberador de Hormônio do Crescimento/biossíntese , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley
17.
Endocr Res ; 21(4): 719-32, 1995 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8582323

RESUMO

Glucocorticoids are known to inhibit GH secretion via somatostatin. The aim of our study was to elucidate the involvement of somatostatin in the GH-releasing action of the alpha 2 agonist clonidine and the cholinergic agent pyridostigmine in conscious, freely-moving rats chronically treated with dexamethasone. After seven days of chronic glucocorticoid treatment, animals received an i.v. injection of either saline (1 ml/kg) or clonidine (150 micrograms/kg) or pyridostigmine (100 micrograms/kg) at -15 min. Three blood samples were then drawn (-10 min, -5 min, and 0 min) to assess the GH response to either clonidine or pyridostigmine alone. After the 0 min sample, saline (1 ml/kg) or GNRH (500 ng/kg) was injected i.v. and additional blood samples were drawn from 5 to 30 min. The GH response to clonidine alone or combined with GNRH in rats treated with dexamethasone was significantly lower (p < 0.05) as compared to vehicle-treated rats. The GH response to pyridostigmine alone or combined with GNRH did not significantly differ between vehicle- and dexamethasone-treated rats. These data suggest that in the rat the mechanism of action of clonidine is mainly to stimulate endogenous GNRH secretion, while pyridostigmine appears to predominantly act by decreasing hypothalamic somatostatin.


Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Clonidina/farmacologia , Hormônio Liberador de Hormônio do Crescimento/efeitos dos fármacos , Hormônio do Crescimento/metabolismo , Hipotálamo/metabolismo , Parassimpatomiméticos/farmacologia , Brometo de Piridostigmina/farmacologia , Animais , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Hormônio do Crescimento/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Masculino , Radioimunoensaio , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
18.
Eur J Clin Chem Clin Biochem ; 33(7): 411-5, 1995 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7548447

RESUMO

The administration of large doses of selenium (Se) to rats leads to reduced serum levels of somatotropin (growth hormone) and insulin-like growth factor-1 (IGF-1), followed by growth retardation. Similar experiments in humans have been contradictory. The effects of wheat Se and selenomethionine supplementation were investigated in healthy, Norwegian women. In study 1, the participants (n = 18) were given Se-rich bread with 100, 200 and 300 micrograms Se daily for 6 weeks. Initial serum Se concentration were 1.5 +/- 0.2 mumol/l (mean +/- SD). Serum Se increased in a dose-dependent manner in the three groups (p < 0.001). There was no effect on somatotropin and IGF-1 at any of the Se doses given. In study 2 (n = 24), the effects of 400 micrograms selenomethionine daily for 15 weeks were studied in a placebo controlled study. In the treatment group, serum Se concentrations increased by more than 100%. There was, however, no effect on serum somatotropin and IGF-1 concentrations, nor was there any effect on IGF-binding proteins 1 and 3. Our results indicate that at normal or slightly increased intakes, Se has no effect on the serum concentrations of these two hormones in healthy individuals.


Assuntos
Hormônio do Crescimento/sangue , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Selênio/farmacologia , Selenometionina/farmacologia , Adulto , Animais , Feminino , Alimentos Fortificados , Hormônio do Crescimento/efeitos dos fármacos , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/efeitos dos fármacos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/efeitos dos fármacos , Placebos , Ratos , Selênio/administração & dosagem , Selenometionina/administração & dosagem , Triticum
19.
Int J Sport Nutr ; 3(3): 290-7, 1993 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8220394

RESUMO

Using a double-blind, crossover protocol, we studied the possible effects of a 4-day combined L-arginine, L-ornithine, and L-lysine supplementation (each 2 g/day, divided into two daily doses) on 24-hr level of serum human growth hormone (hGH) and insulin in 11 competitive weightlifters, ages 19 to 35 yrs. Three similar daily hGH peaks, seemingly preceded by a decrease in serum insulin concentration, were found during both amino acid and placebo supplementation. Supplementation did not affect the physiological variation of serum hGH concentration (treatment and treatment x time interaction: p = 0.43-0.55). Analogously, serum insulin levels were not higher after amino acid supplementation. Therefore the ergogenic value of low-dose oral amino acid supplementation in increasing hGH or insulin secretion seems questionable.


Assuntos
Aminoácidos/farmacologia , Hormônio do Crescimento/efeitos dos fármacos , Levantamento de Peso/fisiologia , Adulto , Aminoácidos/administração & dosagem , Método Duplo-Cego , Esquema de Medicação , Hormônio do Crescimento/sangue , Humanos , Insulina/metabolismo , Masculino
20.
Int J Sport Nutr ; 3(3): 298-305, 1993 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8220395

RESUMO

Amino acids are commonly ingested as ergogenic acids in the belief that they enhance protein synthesis and stimulate growth hormone release. The aim of this study was to determine the acute effect that amino acid supplements have on serum growth hormone (GH) concentration. Seven male body-builders reported to the laboratory on four occasions after an 8-hr fast and ingested, in random order, either a placebo, a 2.4-g arginine/lysine supplement, a 1.85-g ornithine/tyrosine supplement, or a 20-g BovrilR drink. Blood was collected before each treatment and again every 30 minutes for 3 hours for the measurement of serum GH concentration. On a separate occasion, subjects had an intravenous infusion of 0.5 microgram GH-releasing hormone.kg-1 body weight to confirm that GH secretory response was normal. The main finding was that serum GH concentrations were not altered consistently in healthy young males following the ingestion of the amino acid supplements in the quantities recommended by the manufacturers.


Assuntos
Aminoácidos/farmacologia , Hormônio do Crescimento/efeitos dos fármacos , Levantamento de Peso/fisiologia , Administração Oral , Adulto , Aminoácidos/administração & dosagem , Hormônio do Crescimento/administração & dosagem , Hormônio do Crescimento/sangue , Humanos , Masculino
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