Differentiated mTOR but not AMPK signaling after strength vs endurance exercise in training-accustomed individuals

The influence of adenosine mono phosphate (AMP)-activated protein kinase (AMPK) vs Akt-mammalian target of rapamycin C1 (mTORC1) protein signaling mechanisms on converting differentiated exercise into training specific adaptations is not well-established. To investigate this, human subjects were divided into endurance, strength, and non-exercise control groups. Data were obtained before and during post-exercise recovery from single-bout exercise, conducted with an exercise mode to which the exercise subjects were accustomed through 10 weeks of prior training. Blood and muscle samples were analyzed for plasma substrates and hormones and for muscle markers of AMPK and Akt-mTORC1 protein signaling. Increases in plasma glucose, insulin, growth hormone (GH), and insulin-like growth factor (IGF)-1, and in phosphorylated muscle phospho-Akt substrate (PAS) of 160 kDa, mTOR, 70 kDa ribosomal protein S6 kinase, eukaryotic initiation factor 4E, and glycogen synthase kinase 3α were observed after strength exercise. Increased phosphorylation of AMPK, histone deacetylase5 (HDAC5), cAMP response element-binding protein, and acetyl-CoA carboxylase (ACC) was observed after endurance exercise, but not differently from after strength exercise. No changes in protein phosphorylation were observed in non-exercise controls. Endurance training produced an increase in maximal oxygen uptake and a decrease in submaximal exercise heart rate, while strength training produced increases in muscle cross-sectional area and strength. No changes in basal levels of signaling proteins were observed in response to training. The results support that in training-accustomed individuals, mTORC1 signaling is preferentially activated after hypertrophy-inducing exercise, while AMPK signaling is less specific for differentiated exercise.

Hormonal and metabolic responses to repeated cycling sprints under different hypoxic conditions

OBJECTIVE: Sprint exercise and hypoxic stimulus during exercise are potent factors affecting hormonal and metabolic responses. However, the effects of different hypoxic levels on hormonal and metabolic responses during sprint exercise are not known. Here, we examined the effect of different hypoxic conditions on hormonal and metabolic responses during sprint exercise. DESIGN: Seven male subjects participated in three experimental trials: 1) sprint exercise under normoxia (NSE); 2) sprint exercise under moderate normobaric hypoxia (16.4% oxygen) (HSE 16.4); and 3) sprint exercise under severe normobaric hypoxia (13.6% oxygen) (HSE 13.6). The sprint exercise consisted of four 30s all-out cycling bouts with 4-min rest between bouts. Glucose, free fatty acids (FFA), blood lactate, growth hormone (GH), epinephrine (E), norepinephrine (NE), and insulin concentrations in the HSE trials were measured before exposure to hypoxia (pre 1), 15 min after exposure to hypoxia (pre 2), and at 0, 15, 30, 60, 120, and 180 min after the exercise performed in hypoxia. The blood samples in the NSE trial were obtained in normoxia at the same time points as the HSE trials. RESULTS: Circulating levels of glucose, FFA, lactate, GH, E, NE, and insulin significantly increased after all three exercise trials (P < 0.05). The area under the curve (AUC) for GH was significantly higher in the HSE 13.6 trial than in the NSE and HSE 16.4 trials (P < 0.05). A maximal increase in FFA concentration was observed at 180 min after exercise and was not different between trials. CONCLUSION: These findings suggest that severe hypoxia may be an important factor for the enhancement of GH response to all-out sprint exercise.

Susceptibility of reproduction in female pigs to impairment by stress and the role of the hypothalamo-pituitary-adrenal axis

Although it is generally considered that stress can impair reproduction, we suggest that the impact of acute or repeated acute stress or acute or repeated acute elevations of cortisol are of little consequence in female pigs, even if these occur during the series of endocrine events that induce oestrus and ovulation. It is important to understand the impact of acute stress on reproduction because, in the intensive production of livestock, animals are often subjected to short-term challenges. There seems little doubt that reproduction in a proportion of female pigs is susceptible to impairment by severe and prolonged stress or the sustained elevation of cortisol but only when this continues for a substantial period. In female pigs, where reproduction is susceptible to impairment by severe prolonged stress, it is possible that the mediators of this suppression are cortisol, corticotrophin-releasing factor and vasopressin but, in pigs, there is evidence to suggest that adrenocorticotrophic hormone is not involved. Other substances secreted during stress may be involved but these are not considered in this review. It is possible that the mediators of stress act at any level of the hypothalamo-pituitary-ovarian axis. Although a variety of experimental manipulations have provided potential mediators and mechanisms for the stress-induced suppression of reproduction, these experimental manipulations rarely represented physiological circumstances so it is not clear if such mechanisms would be important in a physiological context. The precise mediators and mechanisms by which hormones released during stress may inhibit reproductive processes during severe prolonged stress are yet to be determined.

Influence of sex and gonadal status of sheep on cortisol secretion in response to ACTH and on cortisol and LH secretion in response to stress: importance of different stressors

There are sex differences in the response to stress and in the influence of stress on reproduction which may be due to gonadal steroids but the nature of these differences and the role of the gonads are not understood. We tested the hypotheses that sex and the presence/absence of gonads (gonadal status) will influence the cortisol response to injection of ACTH, insulin-induced hypoglycaemia and isolation/restraint stress, and that sex and gonadal status will influence the secretion of LH in response to isolation/restraint stress. Four groups of sheep were used in each of three experiments: gonad-intact rams, gonadectomised rams, gonad-intact ewes in the mid-luteal phase of the oestrous cycle and gonadectomised ewes. In Experiment 1 (n=4/group), jugular blood samples were collected every 10 min for 6 h; after 3 h, two animals in each group were injected (i.v.) with ACTH and the remaining two animals were injected (i.v.) with saline. Treatments were reversed 5 days later so that every animal received both treatments. Experiment 2 (n=4/group) used a similar schedule except that insulin was injected (i.v.) instead of ACTH. In Experiment 3 (n=5/group), blood samples were collected every 10 min for 16 h on a control day and again 2 weeks later when, after 8 h of sampling, all sheep were isolated and restrained for 8 h. Plasma cortisol was significantly (P<0.05) elevated following injection of ACTH or insulin and during isolation/restraint stress. There were no significant differences between the sexes in the cortisol response to ACTH. Rams had a greater (P<0.05) cortisol response to insulin-induced hypoglycaemia than ewes while ewes had a greater (P<0.05) cortisol response to isolation/restraint stress than rams. There was no effect of gonadal status on these parameters. Plasma LH was suppressed (P<0.05) in gonadectomised animals during isolation/restraint stress but was not affected in gonad-intact animals, and there were no differences between the sexes. Our results show that the sex that has the greater cortisol response to a stressor depends on the stressor imposed and that these sex differences are likely to be at the level of the hypothalamo-pituitary unit rather than at the adrenal gland. Since there was a sex difference in the cortisol response to isolation/restraint, the lack of a sex difference in the response of LH to this stress suggests that glucocorticoids are unlikely to be a major mediator of the stress-induced suppression of LH secretion.

Somatotrophic and thyroid hormones around the onset of lay in broiler breeders under different conditions

Somatotrophic and thyroid hormones were determined around the onset of reproduction in broiler breeders reared in two different housing systems [dark, close-sided house (CH) and conventional, open-sided house (OH)]. In both groups age-related changes were obvious for thyroxine (T-4), growth hormone (GH) and insulin-like growth factor (IGF-1); levels of T-4 decreased, especially between 24 and 28 weeks in both groups; concomitantly GH sharply increased over the same period. A transient peak in triiodothyronine (T-3) occurred between 25 and 27 weeks. The effect of housing was only present after the onset of lay. Between weeks 27-28 and the end of the period studied, the CH group showed higher levels of GH and T-3 but lower T-4 levels as compared to the OH group. A significant increase in GH after onset of lay, without any significant rise in T-3 or in IGF-I, could point to a relative insensitivity to high plasma GH levels. Changes at GH receptor level, together with an increased pituitary GH secretion and/or decreased GH turnover may be expected. This may indicate that hypothalamo-pituitary changes at the onset of lay not only imply changes of gonadotrophic cell function, but also other hormonal axes. The relatively decrease in T-4 without changes in T-3, may point to a decrease in the activity of the thyrotropic axis.

Performance and hormonal profile in broiler chickens fed with different energy levels during post restriction period

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effects of GHR gene polymorphisms on growth and carcass traits in Zebu and crossbred beef cattle

The growth hormone receptor (GHR) is the cell surface receptor for growth hormone (GH) and is required for GH to carry out its effects on target tissues. The objectives of the present study were to estimate the allele and genotype frequencies of the GHR/Alu I gene polymorphism located in the regulatory region in beef cattle belonging to different genetic groups and to determine associations between this polymorphism and growth and carcass traits. Genotyping was performed on 384 animals, including 79 Nellore (Zebu), 30 Canchim (5/8 Charolais+3/8 Zebu), 30 Simmental X Nellore crossbred and 245 Angus x Nellore crossbred cattle. Alleles Alu I(+), Alu I(-) and Alu I(N)-null allele-were evidenced for the GHR/Alu I polymorphism and the frequency of the Alu I(N) allele was significantly higher than the frequency of the Alu I(+) and Alu I(-) alleles in all genetic groups. Genotype Alu I(N/N) of the GHRIAlu I predominated in Nellore animals, while the Alu I(N/+) and Alu I(N/-) predominated in the other genetic groups. In the association studies, traits of interest were analyzed using the General Linear Model (GLM) procedure of the SAS program and least squares means of the genotypes were compared by the Tukey test. Significant associations (P < 0.05) were observed between the Alu I(N/N) genotype of the GHRIAlu I polymorphism and lower weight gain and body weight at slaughter, although a confounding between genotypes and genetic groups may have occurred. (c) 2005 Elsevier B.V. All rights reserved.

Effects of polymorphic microsatellites in the regulatory region of IGF1 and GHR on growth and carcass traits in beef cattle

Growth hormone (GH), insulin-like growth factors 1 and 2 (IGF1 and IGF2) and their associated binding proteins and transmembrane receptors (GHR, IGF1R and IGF2R) play an important role in the physiology of mammalian growth. The objectives of the present study were to estimate the allele and genotype frequencies of microsatellite markers located in the 5'-regulatory region of the IGF1 and GHR genes in beef cattle belonging to different genetic groups and to determine effects of these markers on growth and carcass traits in these animals under an intensive production system. For this purpose, genotyping was performed on 384 bulls including 79 Nellore, 30 Canchim (5/8 Charolais + 3/8 Zebu) and 275 crossbred animals originating from crosses of Simmental (1/2 Simmental, n = 30) and Angus (1/2 Angus, n = 245) sires with Nellore females. The effects of substituting L allele for S allele of GHR microsatellite across Nellore, Canchim and 1/2 Angus were significant for weight gain and body weight (P < 0.05). The IGF1 microsatellite allele substitutions of 229 for 225 within Nellore group and of 225 for 229 within 1/2 Angus were not significant for any of the traits.

GH overexpression causes muscle hypertrophy independent from local IGF-I in a zebrafish transgenic model

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Influence of moderate physical training on the GH/IGF-1 axis in diabetic rats

The influence of moderate physical training on serum growth hormone (GH), insulin-like growth factor -1 (IGF-1) and binding protein ( IGFBP-3) in experimental diabetic rats was investigated. Male Wistar rats were divided into 4 groups, sedentary control (SC), trained control (TC), sedentary diabetic (SD) and trained diabetic (TD). Experimental diabetes was induced of Alloxan (35mg/b.w.) the training program consisted by swimming 5 days/week, 1 h/day, supporting a load of 2.5% b.w., during 6 weeks. Then, the rats were sacrificed and blood was collected for determinations of serum glucose, insulin, GH, IGF-1 and IGFBP-3. Samples of liver were used to evaluate glycogen, protein and DNA contents. The results were analyzed by ANOVA, and Bonferroni test and the significance level was set at 2.5%. Diabetes decreased serum GH, IGF-1, IGFBP-3 and liver glycogen stores in SD group. Physical training promoted increase in serum IGF-1 in both TC and TD groups (SC=82 +/- 15; TC= 1 03 +/- 13; SD=77 +/- 16; TD= 112 +/- 29 ng/ml) and liver glycogen store in TD group when compared to SD (SC=5.2 +/- 1.2; TC= 6.2 +/- 1; SD=2 +/- 0.5; TD=5 +/- 1.8 mg/100mg). Therefore, physical training contributes to the increase in liver glycogen content and to rise of insulin-like growth factor level in diabetic rats. It was concluded that moderate physical training promotes important adaptations related to GH-IGF-1 axis in diabetic organisms.

Effects of swimming training on bone mass and the GH/IGF-1 axis in diabetic rats

The aim of this study was to examine the influence of moderate swimming training on the GH/IGF-1 growth axis and tibial mass in diabetic rats. Male Wistar rats were allocated to one of four groups: sedentary control (SC), trained control (TC), sedentary diabetic (SD) and trained diabetic (TD). Diabetes was induced with alloxan (35 mg/kg b.w.). The training program consisted of a 1 h swimming session/day with a load corresponding to 5% of the b.w., five days/week for six weeks. At the end of the training period, the rats were sacrificed and blood was collected for quantification of the serum glucose, insulin, GH, and IGF-1 concentrations. Samples of skeletal muscle were used to quantify the IGF-1 pepticle content. The tibias were collected to determine their total area, length and bone mineral content. The results were analyzed by ANOVA with P < 0.05 indicating significance. Diabetes decreased the serum levels of GH and IGF-1, as well as the tibial length, total area and bone mineral content in the SD group (P < 0.05). Physical training increased the serum IGF-1 level in the TC and TD groups when compared to the sedentary groups (SC and SD), and the tibial length, total area and bone mineral content were higher in the TD group than in the SD group (P < 0.05). Exercise did not alter the level of IGF-1 in gastrocnemius muscle in nondiabetic rats, but the muscle IGF-1 content was higher in the TD group than in the SD group. These results indicate that swimming training stimulates bone mass and the GH/IGF-1 axis in diabetic rats. (c) 2006 Elsevier Ltd. All rights reserved.

Long-term physical training increases liver IGF-I in diabetic rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

INFLUENCE OF DIETARY-PROTEIN INTAKE AND RECOMBINANT HUMAN SOMATOTROPIN ADMINISTRATION ON GROWTH AND BODY-COMPOSITION OF JUVENILE TAMBACU (A PIARACTUS-MESOPOTAMICUS X COLOSSOMA-MACROPOMUM CROSS)

This experiment was undertaken to study the interaction between level of dietary protein and recombinant human somatotropin (rhGH) administration on performance and body composition of juvenile tambacu (a crossbred Brazilian fish). A total of 72 juvenile tambacu, initially weighing and measuring (mean +/- s.e.m.) 23 +/- 2 g and 9 +/- 0.5 cm, respectively, were randomly divided into 18 groups of 4 fish each. Water temperature was 28 degrees C. Triplicate groups received one of two levels of dietary protein (15 and 30% as fed basis) and one of 3 doses of rhGH (0, 2 and 4 mu g/g) via intraperitoneal injection twice a week for 6 weeks, using a randomized complete block design. Somatotropin was noted to stimulate linear and body weight gain. The higher protein level supported increased growth in weight and length, but there was no interaction between protein level and rhGH dose for either parameter. Protein efficiency ratio and percentage protein deposited showed higher values on diets containing 15% protein. Somatotropin treatment did not significantly affect body composition, but there was a trend towards improved protein retention and reduced carcass lipid. In conclusion, the results of this experiment suggest that rhGH is able to stimulate linear gain in tambacu.

Enhanced nicotine-seeking behavior following pre-exposure to repeated cocaine is accompanied by changes in BDNF in the nucleus accumbens of rats

We investigated the behavioral and molecular interactions between cocaine and nicotine, through evaluating locomotor activity, nicotine intravenous self-administration and gene expression. Locomotor sensitization was induced in male Wistar rats by repeated cocaine (20 mg/kg; i.p.) or saline injections once a day over 7 days. Three days after the last injection, rats were challenged with either saline or cocaine (15 mg/kg; i.p.) and the locomotor activity was measured. The very next day animals received either saline or nicotine (0.4 mg/kg; s.c.) and the locomotor cross-sensitization was tested. Animals were then prepared with intrajugular catheters for nicotine self-administration. Nicotine self-administration patterns were evaluated using fixed or progressive ratio schedules of reinforcement and a 24-h unlimited access binge. Immediately after the binge sessions animals were decapitated, the brains were removed and the nucleus accumbens was dissected. The dynorphin (DYN), μ-opioid receptor (mu opioid), neuropeptide Y (NPY), brain-derived neurotrophic factor (BDNF), tropomyosin-related tyrosine kinase B receptor (TrkB) and corticotropin- releasing factor receptor type 1 (CRF-R1) gene expression were measured by the reverse transcription-polymerase chain reaction (RT-PCR). Pretreatment with cocaine caused sensitization of cocaine motor response and locomotor cross-sensitization with nicotine. In the self-administration experiments repeated cocaine administration caused an increase in the nicotine break point and nicotine intake during a 24 h binge session. © 2013 Elsevier Inc.

Polymorphisms in the ghrelin gene and their associations with milk yield and quality in water buffaloes

Ghrelin is a gastrointestinal hormone that acts in releasing growth hormone and influences the body general metabolism. It has been proposed as a candidate gene for traits such as growth, carcass quality, and milk production of livestock because it influences feed intake. In this context, the aim of this study was to verify the existence of polymorphisms in the ghrelin gene and their associations with milk, fat and protein yield, and percentage in water buffaloes (Bubalus bubalis). A group of 240 animals was studied. Five primer pairs were used and 11 single nucleotide polymorphisms (SNP) were found in the ghrelin gene by sequencing. The animals were genotyped for 8 SNP by PCR-RFLP. The SNP g.960G>A and g.778C>T were associated with fat yield and the SNP g.905T>C was associated with fat yield and percentage and protein percentage. These SNP are located in intronic regions of DNA and may be in noncoding RNA sites or affect transcriptional efciency. The ghrelin gene in buffaloes influences milk fat and protein synthesis. The polymorphisms observed can be used as molecular markers to assist selection. © 2013 American Dairy Science Association.