Serum Growth Hormone Concentrations Research Articles

Efficacy of a capsicum extract on growth, blood parameters and intestinal bacterial population of broilers

Context The ban on antibiotics in broiler feed has led to the need for alternative additives that can be used in poultry production, particularly in tropical climates where animals experience high levels of stress. A capsicum extract (CE), derived from chili peppers, is a potential feed additive that may enhance the performance of broiler chickens. Aims This experiment investigated the effects of CE on the growth performance, blood parameters, and intestinal bacterial population of broilers raised under high stocking density in a tropical region. Methods Four hundred and thirty-two 1-day-old Ross-308 male broiler chicks were divided into six treatments, each with six replicate pens of 12 birds. The experiment followed a randomised complete-block design. Feeding was conducted for 38 days in the following three phases on the basis of breeder recommendations: starter, grower, and finisher. CE was supplemented in the feed at concentrations of 80, 160, 240, and 320 mg/kg. All feeds were pelleted to different sizes for each phase. Growth performance was assessed at the end of each phase. Blood samples were collected to determine the complete blood count (CBC) and serum growth-hormone concentration. Chicks were euthanised using CO2 inhalation, and samples from the jejunum were collected for histological analysis. The caecocolonic contents were sampled for microbiological testing. Key results CE supplementation at concentrations of 160 and 240 mg/kg improved the performance of broilers equivalent to enramycin supplementation at 250 mg/kg, with additional benefits observed in water intake when supplemented at 240 mg/kg. The slight improvement in villous height may have contributed to the enhanced growth performance. Both the lowest (80 mg/kg) and highest (320 mg/kg) supplemented concentrations of CE slightly improved broiler performance compared with the control group. The lowest dose of CE also had a beneficial effect in reducing the E. coli:Lactobacillus ratio. Conclusions It is concluded that CE supplementation may improve performance of broilers under moderate heat-stress conditions by increasing feed and water intake with an enhanced bodyweight gain. Implications A capsicum extract can be used as an antibiotic alternative in broiler production in hot tropical environments.

Acute Hemodynamic, Metabolic, and Hormonal Responses to a Boxing Exergame with and without Blood Flow Restriction in Non-Athlete Young Individuals.

This study aimed to compare acute hemodynamic, metabolic (glucose and blood lactate concentrations), hormonal (growth hormone and normetanephrine), heart rate variability (HRV), and rating of perceived exertion (RPE) responses before and after bouts of a boxing exergame with and without blood flow restriction (BFR) in non-athlete young individuals. Fourteen participants (age: 30 ± 10 y; BMI: 21 ± 3 kg.m-2) participated in two sessions of a 20 min boxing exergame. During week one, the participants were randomly divided into two groups and played against one another under normal (n = 7) and BFR (n = 7) conditions. Over the next exercise session, participants were then reallocated to the opposite condition (normal vs. BFR) for data collection. Hemodynamic, metabolic, HRV, and hormonal parameters were measured before and immediately after the exercise protocols. Playing exergame led to a significant increase in hemodynamic variables (except for diastolic blood pressure) regardless of BFR condition with no between-group differences. Regarding HRV, significant reductions in total power (TP) and low-frequency (LF) waves were identified in the non-BFR group (p < 0.0001) compared with the BFR group. Conversely, a significant increase in very LF (VLF) waves was noted for the BFR group (p = 0.050), compared with the non-BFR group. Significant increases were observed in serum concentrations of growth hormone, normetanephrine, and blood lactate concentration from pre- to post-exercise under both conditions (p ≤ 0.05), with no significant differences between the groups. Moreover, no statistically significant changes were observed in glucose levels. RPE responses were significantly greater (p ≤ 0.05) in the BFR group compared with the non-BFR group throughout the exercise session. We observed similar hemodynamic, hormonal, and metabolic responses after an acute boxing exergame session in young individuals, whether conducted with or without BFR. However, notable differences were observed in certain HRV markers and RPE. Specifically, the inclusion of BFR resulted in an elevation of VLF and a heightened perceived exertion. These findings suggest that BFR may alter cardiac autonomic and perceptual responses during exergaming. Further research is warranted to understand the long-term implications and potential benefits of incorporating BFR into exergaming routines.

Molecular Mechanisms of the Regulation of Liver Cytochrome P450 by Brain NMDA Receptors and via the Neuroendocrine Pathway—A Significance for New Psychotropic Therapies

Recent investigations have highlighted the potential utility of the selective antagonist of the NMDA receptor GluN2B subunit for addressing major depressive disorders. Our previous study showed that the systemic administration of the antagonist of the GluN2B subunit of the NMDA receptor, the compound CP-101,606, affected liver cytochrome P450 expression and activity. To discern between the central and peripheral mechanisms of enzyme regulation, our current study aimed to explore whether the intracerebral administration of CP-101,606 could impact cytochrome P450. The injection of CP-101,606 to brain lateral ventricles (6, 15, or 30 µg/brain) exerted dose-dependent effects on liver cytochrome P450 enzymes and hypothalamic or pituitary hormones. The lowest dose led to an increase in the activity, protein, and mRNA level of CYP2C11 compared to the control. The activities of CYP2A, CYP2B, CYP2C11, CYP2C6, CYP2D, and protein levels of CYP2B, CYP2C11 were enhanced compared to the highest dose. Moreover, CP-101,606 increased the CYP1A protein level coupled with elevated CYP1A1 and CYP1A2 mRNA levels, but not activity. The antagonist decreased the pituitary somatostatin level and increased the serum growth hormone concentration after the lowest dose, while independently decreasing the serum corticosterone concentration of the dose. The findings presented here unveil a novel physiological regulatory mechanism whereby the brain glutamatergic system, via the NMDA receptor, influences liver cytochrome P450. This regulatory process appears to involve the endocrine system. These results may have practical applications in predicting alterations in cytochrome P450 activity and endogenous metabolism, and potential metabolic drug–drug interactions elicited by drugs that cross the blood–brain barrier and affect NMDA receptors.

Lysine-rich rice partially enhanced the growth and development of skeletal system with better skeletal microarchitecture in young rats

Rice is the primary staple food for half of the world's population but is low in lysine content. Previously, we developed transgenic rice with enhanced free lysine content in rice seeds (lysine-rich rice), which was shown safe for consumption and improved the growth in rats. However, the effects of lysine-rich rice on skeletal growth and development remained unknown. In this study, we hypothesized that lysine-rich rice improved skeletal growth and development in weaning rats. Male weaning Sprague–Dawley rats received lysine-rich rice (HFL) diet, wild-type rice (WT) diet, or wild-type rice with various contents of lysine supplementation diet for 70 days. Bone microarchitectures were examined by microcomputed tomography, bone strength was investigated by mechanical test, and dynamics of bone growth were examined by histomorphometric analysis. In addition, we explored the molecular mechanism of lysine and skeletal growth through biochemical testing of growth hormone, bone turnover marker, and amino acid content of rat serum analysis, as well as in a cell culture system. Results indicated that the HFL diet improved rats' bone growth, strength, and microarchitecture compared with the WT diet group. In addition, the HFL diet increased the serum essential amino acids, growth hormone (insulin-like growth factor-1), and bone formation marker concentrations. The cell culture model showed that lysine deficiency reduced insulin-like growth factor-1 and Osterix expression, Akt/mammalian target of rapamycin signaling, and matrix mineralization, and inhibited osteoblast differentiation associated with bone growth. Our findings showed that lysine-rich rice improved skeletal growth and development in weaning rats. A further increase of rice lysine content is highly desirable to fully optimize bone growth and development.

The effect of brain serotonin deficit (TPH2-KO) on the expression and activity of liver cytochrome P450 enzymes in aging male Dark Agouti rats

BackgroundLiver cytochrome P450 (CYP) greatly contributes to the metabolism of endogenous substances and drugs. Recent studies have demonstrated that CYP expression in the liver is controlled by the central nervous system via hormonal pathways. In particular, the expression of hepatic CYPs is negatively regulated by the brain serotoninergic system. The present study aimed to investigate changes in the function of the main liver drug-metabolizing CYP enzymes as a result of serotonin depletion in the brain of aging rats, caused by knockout of brain tryptophan hydroxylase gene (TPH2-KO).MethodsThe hepatic CYP mRNA (qRT-PCR), protein level (Western blotting) and activity (HPLC), and serum hormone levels (ELISA) were measured in Dark Agouti wild-type (WT) male rats (mature 3.5-month-old and senescent 21-month-old) and in TPH2-KO senescent animals.ResultsThe expression/activity of the studied CYPs decreased with age in the liver of wild-type rats. The deprivation of serotonin in the brain of aging males decreased the mRNA level of most of the studied CYPs (CYP1A/2A/2B/3A), and lowered the protein level of CYP2C11 and CYP3A. In contrast, the activities of CYP2C11, CYP3A and CYP2C6 were increased. The expression of cytochrome b5 decreased in aging rats, but increased in TPH2-deficient senescent animals. The serum concentration of growth hormone declined in the aged and further dropped down in TPH2-deficient senescent rats.ConclusionsRat liver cytochrome P450 functions deteriorate with age, which may impair drug metabolism. The TPH2 knockout, which deprives brain serotonin, affects cytochrome P450 expression and activity differently in mature and senescent male rats.

Effects of Acute Loading Induced Fatigability, Acute Serum Hormone Responses and Training Volume to Individual Hypertrophy and Maximal Strength during 10 Weeks of Strength Training

This study investigated whether a strength training session-induced acute fatigue is related to individuals’ strength training adaptations in maximal force and/or muscle hypertrophy, and whether acute responses in serum testosterone (T) and growth hormone (GH) concentrations during the training sessions would be associated with individual neuromuscular adaptations. 26 males completed the 10-week strength-training intervention, which included fatiguing dynamic leg press acute loading bouts (5 x 10 RM) at weeks two, four, six, and ten. Blood samples were collected before and after the loading and after 24h of recovery for serum T, GH, and cortisol (C) concentrations at weeks 2, 6, and 10. The cross-sectional area of the vastus lateralis was measured by ultrasonography. Isometric force measurements were performed before and immediately after loadings, and loading-induced acute decrease in maximal force was reported as the fatigue percentage. The subjects were split into three groups according to the degree of training-induced muscle hypertrophy after the training period. Increases in isometric force were significant for High Responders (HR, n = 10) (by 24.3 % ± 17.2, p = 0.035) and Medium Responders (MR, n = 7) (by 23.8 % ± 5.5, p = 0.002), whereas the increase of 26.2 % (±16.5) in Low Responders (LR, n = 7) was not significant. The amount of work (cm + s) increased significantly at every measurement point in all the groups. A significant correlation was observed between the fatigue percentage and relative changes in isometric force after the training period for the whole group (R = 0.475, p = 0.022) and separately only in HR (R = 0.643, p = 0.049). Only the HR group showed increased acute serum GH concentrations at every measurement point. There was also a significant acute increase in serum T for HR at weeks 6 and 10. HR showed the strongest correlation between acute loading-induced fatigue and isometric force gains. HR was also more sensitive to acute increases in serum concentrations of T and GH after the loading. Acute fatigue and serum GH concentrations may be indicators of responsiveness to muscle strength gain and, to some extent, muscle hypertrophy.

Effects of Acute Loading Induced Fatigability, Acute Serum Hormone Responses and Training Volume to Individual Hypertrophy and Maximal Strength during 10 Weeks of Strength Training.

This study investigated whether a strength training session-induced acute fatigue is related to individuals' strength training adaptations in maximal force and/or muscle hypertrophy, and whether acute responses in serum testosterone (T) and growth hormone (GH) concentrations during the training sessions would be associated with individual neuromuscular adaptations. 26 males completed the 10-week strength-training intervention, which included fatiguing dynamic leg press acute loading bouts (5 x 10 RM) at weeks two, four, six, and ten. Blood samples were collected before and after the loading and after 24h of recovery for serum T, GH, and cortisol (C) concentrations at weeks 2, 6, and 10. The cross-sectional area of the vastus lateralis was measured by ultrasonography. Isometric force measurements were performed before and immediately after loadings, and loading-induced acute decrease in maximal force was reported as the fatigue percentage. The subjects were split into three groups according to the degree of training-induced muscle hypertrophy after the training period. Increases in isometric force were significant for High Responders (HR, n = 10) (by 24.3 % ± 17.2, p = 0.035) and Medium Responders (MR, n = 7) (by 23.8 % ± 5.5, p = 0.002), whereas the increase of 26.2 % (±16.5) in Low Responders (LR, n = 7) was not significant. The amount of work (cm + s) increased significantly at every measurement point in all the groups. A significant correlation was observed between the fatigue percentage and relative changes in isometric force after the training period for the whole group (R = 0.475, p = 0.022) and separately only in HR (R = 0.643, p = 0.049). Only the HR group showed increased acute serum GH concentrations at every measurement point. There was also a significant acute increase in serum T for HR at weeks 6 and 10. HR showed the strongest correlation between acute loading-induced fatigue and isometric force gains. HR was also more sensitive to acute increases in serum concentrations of T and GH after the loading. Acute fatigue and serum GH concentrations may be indicators of responsiveness to muscle strength gain and, to some extent, muscle hypertrophy.

Promotion of longitudinal bone growth by the intake of oat and green onion root water extracts in weaning rats through stimulating growth hormone secretion and elevating gut microbiota related to nervous system-related pathway

We determined whether oral oat and green onion water extracts (GOO) supplementation could stimulate longitudinal bone growth in weaning rats. Fistuloside A, B, and C in the green onions and 26-desglucoavenacoside A and B and avenacoside A in the oats lowered the binding energy of growth differentiation factor-5 (GDF5) and insulin-like growth factor-1 receptor (IGF1R). After a 4-week treatment, serum growth hormone (GH) and osteoprotegerin concentrations in the High-GOO group (500 mg/kg body weight) were similar to those of the Positive-control. The femur and tibia lengths promoting the proliferative and hypertrophic zones of the growth plate in the High-GOO were also similar to Positive-control. Along with increasing serum propionate and butyrate concentrations, cecal bacteria in the High-GOO were higher in virus infection, steroid and sesquiterpenoid biosynthesis, and nervous system-related pathways than the Control in the metagenome function. It suggested that gut bacteria potentially enhanced bone growth by improving immunity and neurological activity. In conclusion, GOO increased leg length by enhancing the proliferation of the growth plate as much as GH treatment by preventing gut dysbiosis.

A comparison of average daily gain, apparent digestibilities, energy balance, rumen fermentation parameters, and serum metabolites between yaks (Bos grunniens) and Qaidam cattle (Bos taurus) consuming diets differing in energy level.

Yaks (Bos grunniens), indigenous to the harsh Qinghai-Tibetan Plateau, are well adapted to the severe conditions, and graze natural pasture without supplements all year round. Qaidam cattle (Bos taurus), introduced to the Qinghai-Tibetan Plateau 1,700 years ago, are raised at a lower altitude than yaks, provided with shelter at night and offered supplements in winter. Based on their different backgrounds, we hypothesized that yaks have lower energy requirements for maintenance than cattle. To test this hypothesis, we measured average daily gain (ADG), apparent digestibilities, energy balance, rumen fermentation parameters, and serum metabolites in growing yaks and cattle offered diets differing in metabolizable energy (ME) levels (6.62, 8.02, 9.42 and 10.80MJ/kg), but with the same crude protein concentration. Six castrated yaks (155±5.8kg) and 6 castrated Qaidam cattle (154±8.0kg), all 2.5 years old, were used in 2 concurrent 4×4 Latin square designs. Neutral and acid detergent fiber digestibilities were greater (P<0.05) in yaks than in cattle, and decreased linearly (P<0.05) with increasing dietary energy level; whereas, digestibilities of dry matter, organic matter, crude protein and ether extract increased (P<0.05) linearly with increasing energy level. The ADG was greater (P<0.001) in yaks than in cattle, and increased (P<0.05) linearly with increasing energy levels. From the regressions of ADG on ME intake, the estimated ME requirement for maintenance was lower (P<0.05) in yaks than in cattle (0.43 vs. 0.57MJ/kg BW0.75). The ratios of digestible energy (DE):gross energy and ME:DE were higher (P<0.05) in yaks than in cattle, and increased (P<0.05) linearly with increasing dietary energy level. Ruminal pH decreased (P<0.05), whereas concentrations of total volatile fatty acids (VFAs) and ammonia increased (P<0.01) with increasing dietary energy level, and all were greater (P<0.05) in yaks than in cattle. Concentrations of ruminal acetate and iso-VFAs were greater (P<0.05), whereas propionate was lower (P<0.05) in yaks than in cattle; acetate decreased (P<0.001), whereas butyrate and propionate increased (P<0.001) linearly with increasing dietary energy level. Serum concentrations of β-hydroxybutyrate were lower (interaction, P<0.001) in yaks than in cattle fed diets of 9.42 and 10.80MJ/kg, whereas non-esterified fatty acids were greater (interaction, P<0.01) in yaks than in cattle fed diets of 6.62 and 8.02MJ/kg. Concentrations of serum leptin and growth hormone were greater in yaks than in cattle and serum insulin and growth hormone increased (P<0.01) linearly with increasing dietary energy level. Our hypothesis that yaks have lower energy requirements for maintenance than cattle was supported. This lower requirement confers an advantage to yaks over Qaidam cattle in consuming low energy diets during the long winter on the Qinghai-Tibetan Plateau.

Effects of Bacillus licheniformis and Combination of Probiotics and Enzymes as Supplements on Growth Performance and Serum Parameters in Early-Weaned Grazing Yak Calves

Early weaning is an effective strategy to improve cow feed utilization and shorten postpartum intervals in cows; however, this may lead to poor performance of the weaned calves. This study was conducted to test the effects of supplementing milk replacer with Bacillus licheniformis and a complex of probiotics and enzyme preparations on body weight (BW), size, and serum biochemical parameters and hormones in early-weaned grazing yak calves. Thirty two-month-old male grazing yaks (38.89 ± 1.45 kg body weight) were fed milk replacer at 3% of their BW and were randomly assigned to three treatments (n = 10, each): T1 (supplementation with 0.15 g/kg Bacillus licheniformis), T2 (supplementation with a 2.4 g/kg combination of probiotics and enzymes), and a control (without supplementation). Compared to the controls, the average daily gain (ADG) from 0 to 60 d was significantly higher in calves administered the T1 and T2 treatments, and that from 30 to 60 d was significantly higher in calves administered the T2 treatment. The ADG from 0 to 60 d was significantly higher in the T2- than in the T1-treated yaks. The concentration of serum growth hormone, insulin growth factor-1, and epidermal growth factor was significantly higher in the T2-treated calves than in the controls. The concentration of serum cortisol was significantly lower in the T1 treatment than in the controls. We concluded that supplementation with probiotics alone or a combination of probiotics and enzymes can improve the ADG of early-weaned grazing yak calves. Supplementation with the combination of probiotics and enzymes had a stronger positive effect on growth and serum hormone levels, compared to the single-probiotic treatment with Bacillus licheniformis, providing a basis for the application of a combination of probiotics and enzymes.

Reduced circulating growth hormone and insulin-like growth factor-1 and delayed growth of premature rats are aggravated by longer daily duration of chronic intermittent hypoxia exposure.

This study mainly aimed to investigate the effect of daily duration of chronic intermittent hypoxia (CIH) exposure on circulating growth hormone (GH)/insulin-like growth factor-1 (IGF-1) concentrations and body weight changes of premature rats. 40 healthy male SD rats aged six weeks were enrolled in this study. These rats were randomly divided into four groups (n = 10 per group), including normal control (NC) group (normal oxygen exposure every day), CIH-1 group (daily CIH exposure for 2 h), CIH-2 group (daily CIH exposure for 4 h), and CIH-3 group (daily CIH exposure for 8 h). The serum GH/IGF-1 concentrations and body weights in all rats were determined after 30 days of normal oxygen or CIH exposure. No significant difference was found with respect to the baseline body weight among the four groups of rats. After establishments of animal models with a duration of 30 days, significant differences were found respect to body weight, body weight changes, and serum GH/IGF-1 concentrations among the four groups of rats with a same trend (all P < 0.05): the highest values were all in NC group rats, followed CIH-1 group, CIH-2 group, and CIH-3 group rats. Among all the rats, the body weight changes correlated significantly with both serum GH and IGF-1 concentrations (both P < 0.05). CIH decreases circulating GH/IGF-1 concentrations and causes growth delay in premature rats. Such effects could be aggravated by increased daily duration of CIH exposures.

Reduced Growth Hormone Predicts Worsening Adipose Tissue Insulin Resistance in Adults with Obesity

Objectives: Adipose tissue distribution and glucose metabolism differ from adults with normal weight to adults with obesity. Growth hormone (GH) is closely related to obesity. Few studies have investigated the role of GH in adipose tissue insulin resistance (Adipo-IR). Herein, we investigated GH level and Adipo-IR in adults ranging from normal weight to obesity and the potential association between GH and Adipo-IR. Methods: A total of 1,017 participants had their body mass index (BMI), GH, and Adipo-IR evaluated. Based on the BMI, participants were assigned to five groups from normal weight to class 3 obesity; based on the GH level tertiles, participants were divided into low-, medium-, and high-GH groups. Results: In total, the GH level was negatively correlated with the BMI and Adipo-IR index (r = −0.32 and −0.22, respectively; both p < 0.001). The GH level gradually decreased, and Adipo-IR progressively increased from normal weight to class 3 obesity (all p < 0.001). Compared with the low-GH group, the reductions in the BMI, homeostasis model assessment of insulin resistance index, and homeostasis model assessment of β-cell function were more significant in both medium-GH and high-GH groups (all p < 0.05). Additionally, the Adipo-IR index in the high-GH group was significantly lower than that in the low-GH group (p < 0.001). For the multivariate regression analysis, serum GH concentration was an independent protective factor against Adipo-IR (β = −0.013, 95% CI: −0.025 to −0.001, p = 0.028). Conclusions: A marked suppression of GH level occurs in the adults with severe obesity. GH might be an important metabolic regulator associated with Adipo-IR.

Acute Hormonal Responses to Multi-Joint Resistance Exercises with Blood Flow Restriction.

The purpose of this study was to investigate the acute effects of multi-joint resistance exercises (MJRE) with blood flow restriction on hormonal responses. Ten men participated in the study and underwent two experimental protocols in random order: four sets (30, 15, 15, and 15 reps, respectively) of MJRE (half squat and horizontal chest press) were performed with 20% of 1RM and a rest time between sets of 30 s, combined with intermittent blood flow restriction (LI + BFR protocol); and four sets (8, 8, 8, 20 reps, respectively) of the same MJRE performed with 75% of 1RM load (HI protocol), with a 90 s rest between the first three sets and 30 s between the third to the fourth set. Blood samples were collected before (PRE), immediately after (POST), and 15 min after the performance of MJRE (POST15). A time effect was observed for growth hormone (GH) and insulin-like-growth-factor-1-binding-protein-3 (IGFPB-3), but no protocol effects or interactions between protocol and times were observed (p > 0.05). There was no effect of either protocol or time (p > 0.05) on total testosterone, free testosterone, or cortisol concentrations. However, significant (p < 0.05) increases were observed in the GH serum concentrations of 2072.73% and 2278.5%, HI, and LI + BFR protocols, respectively, from the PRE to POST15 test. In addition, there was an increase of 15.30% and 13.29% in the IGFPB-3 concentrations (p < 0.05) from PRE to POST0 times for HI and LI + BFR protocols, respectively. Furthermore, there was a decrease of −6.17% and −11.54%, p = 0.00, between the times POST0 to POST15 in the IGFPB-3 for the HI and LI + BFR protocols, respectively. It is concluded that multi-joint resistance exercises combined with intermittent blood flow restriction seemed to promote acute hormonal responses in a manner similar to traditional exercise with high loads. Future studies may investigate whether chronic use of LI + BFR with MJRE may promote muscle hypertrophy.

Castration alters the cecal microbiota and inhibits growth in Holstein cattle.

To determine the effects of castration on growth performance, serum hormone levels, cecal microbiota composition, and metabolites in cattle. A total of 18 Holstein bulls and steers were divided into bull and steer groups and randomly assigned to 3 pens (3 cattle per pen, and each cattle were separated by a fence) to determine the average daily gain (ADG), daily dry matter intake (DMI), and feed efficiency (G/F). After the finishing trial, six cattle per group were randomly slaughtered. Serum was collected to measure the hormone concentration, and the cecal content was collected to measure the pH, short-chain fatty acids, and digestive enzyme activities. Metagenome sequencing and untargeted metabolomics were used to investigate the microbiota composition, functional profiles, and differential metabolites of the cecal contents. We found that castration significantly decreased ADG, DMI, and G/F in cattle (P < 0.05). The serum testosterone, thyroxine, growth hormone (P < 0.05), and triiodothyronine (P < 0.01) concentrations significantly decreased in the steer group when compared to those of the bull group. The activities of cellulase, xylanase, pectinase, and β-glucosidase (P < 0.05) significantly decreased in the steer group, whereas the activities of lipase and α-amylase significantly increased. Moreover, castration significantly decreased the relative abundance of Ruminococcaceae_bacterium, Treponema_porcinum, Oscillibacter_sp. (P < 0.05), and Alistipes_senegalensis (P < 0.01), whereas the relative abundance of Phocaeicola_plebeius (P < 0.05) was significantly increased. Also, the relative abundance of Phocaeicola_plebeius was negatively correlated with testosterone levels, and the function of the cecal microbiota was enriched in the GH29 and GH97 families in the steer group. Metabolomic analysis indicated that castration increased the levels of L-valine, L-phenylalanine, L-aspartic acid, L-isoleucine, L-lysine, methionine, L-glutamic acid, and L-leucine, while decreasing the levels of α-ketoglutaric acid through the 2-oxocarboxylic acid metabolism pathway. In addition, α-ketoglutaric acid was negatively correlated with Oscillibacter_sp. (P < 0.01). Overall, castration can inhibit cattle growth by altering the composition of the cecal microbiota. Therefore, this study provides a theoretical and practical basis for improving the growth performance of steers.

Prenatal acrylamide exposure results in time-dependent changes in liver function and basal hematological, and oxidative parameters in weaned Wistar rats

Acrylamide (ACR) is a toxic compound commonly found in fried, baked and heat-processed starchy foods. The current study investigated the time-dependent effects of maternal exposure to non-toxic ACR doses on the oxidative stress, liver function, and basal blood morphology of the rat offspring. Pregnant, Wistar rats were randomly divided into the control group or the groups administrated with ACR (3 mg/kg b.w./day): long exposure for 15 days, medium exposure for 10 days and short exposure for 5 days during pregnancy. Body mass, blood morphology and hematology, serum concentrations of growth hormone, IGF-1, TNF-α, IL-1β, IL-6 and insulin, liver histomorphometry, liver activity of beclin1, LC2B and caspase3, markers of oxidative stress and the activity of antioxidative enzymes in blood serum and the liver were measured in offspring at weaning (postnatal day 21). Even short prenatal exposure to ACR led to oxidative stress and resulted in changes in liver histomorphometry and upregulation of autophagy/apoptosis. However, the most significant changes were observed following the long period of ACR exposure. This study has shown for the first time that ACR is responsible for changes in body mass in a time-dependent manner, which could lead to more serious illnesses like overweight and diabetes later in life.

Effect of long-acting growth hormone treatment on endogenous growth hormone secretion in prepubertal patients with idiopathic short stature: A preliminary study

Long-acting growth hormone (LAGH) is emerging to be a new preparation for treatment of short stature. We aimed to determine whether 12-month treatment with LAGH in patients with idiopathic short stature has an effect on the nocturnal endogenous growth hormone (GH) secretion and metabolic consequences and efficacy. Participants included 10 GH-naïve prepubertal children with idiopathic short stature (ISS). One patient was withdrawn due to own decline during study. Participants were randomized on a 1:1 ratio to receive either a daily GH (0.37 mg/kg/week) or once-weekly LAGH (0.7 mg/kg/week) over a 12-month period. Nocturnal endogenous GH secretory profiles obtained from 12-h blood samplings at 30-min interval were assessed at baseline and 2 weeks after the completion of GH treatment. Post-treatment changes in height velocity, height standard deviation score (SDS), metabolic parameters, and adverse events were measured. A total of 4 patients received LAGH, and 5 patients received daily GH. Nocturnal endogenous GH secretory profiles, such as mean serum GH concentrations, frequency, amplitude, interpulse interval of spontaneous GH secretory bursts, and mass of GH released per secretory burst were similar at baseline and after 12-month treatment in both groups. The efficacy and safety after LAGH treatment for 12 months were similar to those of daily GH. In conclusions, these findings indicated that LAGH does not suppress endogenous GH secretion, and can be used for treatment of non-GH deficient short stature with similar efficacy and safety compared to daily GH. These may contribute to define and develop treatment and follow-up protocols for LAGH use in ISS patients.

Overactivation of hepatic mechanistic target of rapamycin kinase complex 1 (mTORC1) is associated with low transcriptional activity of transcription factor EB and lysosomal dysfunction in dairy cows with clinical ketosis

Ketosis occurs most frequently in the peripartal period and is associated with liver injury and steatosis. Lysosomes serve as the terminal degradative station and contribute to liver homeostasis through their role in the digestion of dysfunctional organelles and lipid droplets. Transcription factor EB (TFEB) has been identified as a master regulator of lysosomal function. Thus, the objective of the present study was to investigate the status of lysosomal function and TFEB transcriptional activity and potential changes in abundance of upstream effectors of TFEB identified in nonruminants, including mechanistic target of rapamycin kinase complex 1 (mTORC1), protein kinase B (Akt), glycogen synthase kinase β (GSK3β), and extracellular signal-regulated kinase1/2 (ERK1/2), and to explore which factor induces the above changes. Liver and blood samples were collected from healthy cows (n = 10) and ketotic cows (n = 10) that had a similar number of lactations (median = 3, range = 2-4) and days in milk (median = 6 d, range = 3-9 d). Calf hepatocytes were isolated from Holstein calves and treated with 10 ng/mL growth hormone (GH), 3.0 mM β-hydroxybutyrate (BHB), 1.5 ng/mL interleukin-18 (IL-18), 0.15 ng/mL tumor necrosis factor-α (TNF-α), or 1.2 mM free fatty acid (FFA) for 12 h. Serum levels of FFA and activities of alanine aminotransferase and aspartate aminotransferase were greater in ketotic cows, whereas glucose was lower. Additionally, ketotic dairy cows exhibited higher serum concentrations of GH, IL-18, and TNF-α, and lower serum concentration of insulin. The lower protein abundance of lysosome-associated membrane protein 1 (LAMP1) and mRNA abundance of LAMP1 indicated that hepatic lysosomal mass was lower in ketotic cows. Furthermore, lower protein abundance of cathepsin D (CTSD) and mRNA abundance of CTSD and V0 domain of the vacuolar ATPase along with lower activity of β-N-acetylglucosaminidase indicated impairment in hepatic lysosomal function due to ketosis. The lower nuclear abundance, total protein, and mRNA abundance of TFEB and peroxisome proliferator-activated receptor γ coactivator 1 α along with greater phosphorylated (p)-TFEB in the liver of ketotic cows indicated an impairment of hepatic TFEB transcriptional activity. The protein abundances of phosphorylated mTOR (p-mTOR) and its downstream effectors ribosomal protein S6 kinase B (RPS6KB) and eukaryotic factor 4E-binding protein 1 (EIF4EBP1) were greater, whereas p-Akt, p-GSK3β, and p-ERK1/2 were lower in the liver of ketotic cows. Importantly, elevated phosphorylation of mTOR, RPS6KB, and EIF4EBP1 was observed in calf hepatocytes treated with GH, BHB, IL-18, TNF-α, and FFA. Moreover, BHB, TNF-α, and FFA, not GH and IL-18, reduced TFEB transcriptional activity and impaired lysosomal function in calf hepatocytes. Taken together, these data suggest that BHB, TNF-α, and FFA overactivate the hepatic mTORC1 signaling pathway during ketosis and further impaired TFEB transcriptional activity and lysosomal function, which may contribute to liver injury and steatosis.

The Selective NMDA Receptor GluN2B Subunit Antagonist CP-101,606 with Antidepressant Properties Modulates Cytochrome P450 Expression in the Liver.

Recent research indicates that selective NMDA receptor GluN2B subunit antagonists may become useful for the treatment of major depressive disorders. We aimed to examine in parallel the effect of the selective NMDA receptor GluN2B subunit antagonist CP-101,606 on the pituitary/serum hormone levels and on the regulation of cytochrome P450 in rat liver. CP-101,606 (20 mg/kg ip. for 5 days) decreased the activity of CYP1A, CYP2A, CYP2B, CYP2C11 and CYP3A, but not that of CYP2C6. The alterations in enzymatic activity were accompanied by changes in the CYP protein and mRNA levels. In parallel, a decrease in the pituitary growth hormone-releasing hormone, and in serum growth hormone and corticosterone (but not T3 and T4) concentration was observed. After a 3-week administration period of CP-101,606 less changes were found. A decrease in the CYP3A enzyme activity and protein level was still maintained, though no change in the mRNA level was found. A slight decrease in the serum concentration of corticosterone was also maintained, while GH level returned to the control value. The obtained results imply engagement of the glutamatergic system in the neuroendocrine regulation of cytochrome P450 and potential involvement of drugs acting on NMDA receptors in metabolic drug–drug interactions.

Fresh and cryopreserved semen, minerals, hormones and health characteristics in response to reciprocal combinations of vitamin D3 and 25-hydroxyvitamin D3 in the mature and prepubertal Holstein bulls' diet

The objective of this study was to evaluate the effect of supplementation of 25-hydroxyvitamin D3 (25(OH)VD3) instead of vitamin D3 on the quality and seminal plasma antioxidant indicators of fresh and cryopreserved semen, serum minerals, vitamin D3 status, hormone levels, blood biochemistry, antioxidant and immune function in different age of bulls. Thirty-two Holstein bulls (16 bulls aged 24–36 months and weighted 727 ± 99.0 kg; 16 bulls aged 12 months and weighted 332 ± 24.9 kg) randomly assigned to 1 of 4 treatments in a 2 × 2 factorial arrangement with 2 sources of vitamin D3 (vitamin D3 or 25(OH)VD3) fed at 300 IU/kg dry matter intake and two different age of bull (maturity or prepuberty) through a 60 day period. Bulls were tied in individual pens without access to sunlight. Bulls fed 25(OH)VD3 had greater semen concentration (P = 0.03), sperms motility (P = 0.02), viability (P < 0.001), membrane integrity (P < 0.001) and seminal plasma antioxidant capacity (P < 0.05) at fresh stage compared with bulls fed vitamin D3. In addition, 25(OH)VD3 increased sperms motility (P = 0.02) and membrane integrity (P = 0.04) in cryopreserved semen. Feeding 25(OH)VD3 increased serum total calcium (P = 0.03), total phosphorus (P < 0.001), 25(OH)VD3 (P < 0.001), 1,25-dihydroxyvitamin D3 (P < 0.001) compared with dietary vitamin D3. Feeding 25(OH)VD3 improved concentrations of serum estradiol (P = 0.02), testosterone (P = 0.003) and growth hormone (P < 0.001) and decreased serum cortisol (P = 0.01). Lower blood urea nitrogen (P = 0.005), creatinine (P = 0.02), aspartate aminotransferase (P = 0.005) and higher serum glucose (P = 0.03) were observed in the 25(OH)VD3. Dietary 25(OH)VD3 increased serum glutathione (P = 0.001) and immunoglobulin M (P = 0.03) and decreased malondialdehyde (P = 0.04) compared to those fed vitamin D3. The total antioxidant capacity was affected by interaction of age and vitamin D source (P < 0.001). In conclusion, replacing vitamin D3 with 25(OH)VD3 improved semen quality and benefited health of the mature and prepubertal Holstein bulls.

The Influence of Long-Term Treatment with Asenapine on Liver Cytochrome P450 Expression and Activity in the Rat. The Involvement of Different Mechanisms.

Therapy of schizophrenia requires long-term treatment with a relevant antipsychotic drug to achieve a therapeutic effect. The aim of the present study was to investigate the influence of prolonged treatment with the atypical neuroleptic asenapine on the expression and activity of rat cytochrome P450 (CYP) in the liver. The experiment was carried out on male Wistar rats. Asenapine (0.3 mg/kg s.c.) was administered for two weeks. The levels of CYP mRNA protein and activity were determined in the liver and hormone concentrations were measured in the pituitary gland and blood serum. Asenapine significantly decreased the activity of CYP1A (caffeine 8-hydroxylation and 3-N-demethylation), CYP2B, CYP2C11 and CYP3A (testosterone hydroxylation at positions 16β; 2α and 16α; 2β and 6β, respectively). The neuroleptic did not affect the activity of CYP2A (testosterone 7α-hydroxylation), CYP2C6 (warfarin 7-hydroxylation) and CYP2E1 (chlorzoxazone 6-hydroxylation). The mRNA and protein levels of CYP1A2, CYP2B1, CYP2C11 and CYP3A1 were decreased, while those of CYP2B2 and CYP3A2 were not changed. Simultaneously, pituitary level of growth hormone-releasing hormone and serum concentrations of growth hormone and corticosterone were reduced, while that of triiodothyronine was enhanced. In conclusion, chronic treatment with asenapine down-regulates liver cytochrome P450 enzymes, which involves neuroendocrine mechanisms. Thus, chronic asenapine treatment may slow the metabolism of CYP1A, CYP2B, CYP2C11 and CYP3A substrates (steroids and drugs). Since asenapine is metabolized by CYP1A and CYP3A, the neuroleptic may inhibit its own metabolism, therefore, the plasma concentration of asenapine in patients after prolonged treatment may be higher than expected based on a single dose.