Hepatic Insulin-like Growth factor-I Research Articles

Suitable dietary Myo-inositol supplementations improve growth, immunity and antioxidant properties of hybrid grouper (Epinephelus. fuscoguttatus♀ × E. lanceolatus♂) fed low-fishmeal diets

A six-week feeding trial was carried out to evaluate the effects of different dietary Myo-inositol (MI) levels on growth, feed efficiency, immunity, and antioxidant properties of juvenile hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂) fed low-fishmeal diets. Seven experimental diets were made to contain 50, 100, 169, 241, 309, 386, and 459 mg/kg of MI (analyzed values, dry matter basis), being abbreviated as MI-50, MI-100, MI-169, MI-241, MI-309, MI-386, and MI-459, and each MI treatment had three replicates. Twelve fish (average initial body weight: 18.7 ± 0.1 g) were allocated to each replicate, being hand-fed their diets to apparent satiation on 8:00 am and 16:30 pm. The results indicated that within the range of 50–241 mg/kg dietary inositol, weight gain percentage (WG%), feed efficiency (FE) and protein efficiency ratio (PER) were increased with the increasing of MI, and above the 241 mg/kg, they were dropped, especially at 386 and 459 mg/kg. According to the broken-line regression analysis conducted to assess the relationship between WG% and dietary MI levels, the optimum MI dose was 267.9 mg/kg (dry weight) in the low-fishmeal diet of hybrid grouper. Condition factor (CF), viscerosomatic index (VSI), hepatosomatic index (HSI), and intestinal index (ISI) were significantly (P < 0.05) affected by dietary MI levels, varying with a similar trend as WG%. Fish fed MI-241 had the highest values of serum lysozyme (LZM), hepatic total antioxidant capacity (T-AOC) as well as the relative mRNA level of hepatic insulin-like growth factor-Ⅰ (IGF-Ⅰ) among all treatments. In conclusion, optimum dietary MI requirement for the maximal growth of hybrid grouper was 267.9 mg/kg, and suitable dietary MI supplementations improve growth, immunity, and antioxidant properties of juvenile hybrid grouper fed low-fishmeal diets.

Abomasal Nitrogen Flow Affects the Relationship between Dietary Nitrogen and Insulin-Like Growth Factor-I in Growing Lambs

Twelve abomasally cannulated wether lambs were fed isocaloric diets containing 9, 12 or 15% crude protein to determine insulin-like growth factor-I (IGF-I) responses to altered abomasal nitrogen flow and nitrogen status. Lambs were offered 1100 g/d of their respective diets. Voluntary feed consumption was not affected by nitrogen intake. Ruminal and total tract digestibilities of dry matter, organic matter and nitrogen increased linearly (P < 0.05) with increased dietary nitrogen. Abomasal flows of total, bacterial and rumen escape nitrogen increased (linear, P < 0.01), whereas dry matter and organic matter flows decreased (linear, P < 0.01). Total amino acid flow was greater (linear, P < 0.01) in lambs fed additional nitrogen due to increased (linear, P < 0.01) flows of essential and nonessential amino acids. Nitrogen retention and blood urea nitrogen increased linearly (P < 0.01). Serum IGF-I concentrations and relative hybridization intensity of hepatic IGF-I mRNA increased (linear, P < 0.05) as lambs consumed more nitrogen. Serum IGF-I and hepatic IGF-I mRNA were correlated positively (P < 0.05) with nitrogen intake and abomasal flows of nitrogen and various amino acids. These data provide evidence of a relationship between abomasal amino acid flow, as influenced by nitrogen intake, and hepatic gene expression and serum concentrations of IGF-I in growing lambs.

Growth and Hepatic Insulin-Like Growth Factor-I Gene Expression in Dominant and Subordinate Oreochromis Niloticus L Under Limited Period of Physical Interaction

Social stress is known to regulate several aspects of the teleost physiology. This study explored the influence of limited period of physical interaction on growth and hepatic insulin-like growth factor-I (IGF-I) messenger RNA (mRNA) expression of the fish. Twenty all-male Oreochromis niloticus were isolated for 10 days and were used in a social pair study. After the social interaction was settled, dominant and subordinate individuals in a pair were reared separately in one aquarium separated by glass divider. The fish were fed at the same rate daily to remove the possible effect of nutrition. The glass divider was removed 10 min daily for social interaction. Weight was monitored on Days 2, 7 and 14 during the experimental period, then hepatic IGF-I mRNA expression was quantified. During the 14 days social experiment, mean specific growth rate of dominant fish (1.6%·day−1) was significantly higher (P<0.01) than that of the subordinate fish (0.9%·day−1). Dominant fish also had 2.5 fold significantly higher (P<0.05) mean IGF-I mRNA expression than that of subordinate fish. These indicate that even under limited period of physical contact but with period of visual communication, social status regulates growth and hepatic IGF-I gene expression in this species of fish. There was also a significant positive correlation (r = 0.52; P<0.01) between growth and IGF-I mRNA level which supports the previous studies that hepatic IGF-I gene expression has a potential utility as an instantaneous growth rate indicator for O. niloticus.

α7 Nicotinic Acetylcholine Receptor Agonists Regulate Inflammation and Growth Hormone Resistance in Sepsis.

During sepsis the normal induction of circulating insulin-like growth factor-I (IGF-I) by growth hormone (GH) action on liver is attenuated, a phenomenon called hepatic GH resistance. Hepatic GH resistance can be caused by cytokine-mediated activation of the NF-κB pathway which interferes with normal GH-signaling. The afferent and efferent fibers of the vagus nerve are integral to the cholinergic anti-inflammatory pathway (CAP) which attenuates hepatic TNFα production by activating the α7 nicotinic acetylcholine receptor (α7nAChR). We examined the effects of selective afferent vagotomy (SAV) and α7nAChR activation on sepsis-induced mortality, hepatic and systemic inflammation, the GH/IGF system and hepatic GH resistance using Sprague Dawley (SD) rats, C57BL/6 wild type (WT) mice, and α7nAChR knockout (KO) mice. Capsaicin was used to perform SAV and GTS-21 (α7nAChR agonist) was used to activate the α7nAChR. Sepsis-induced mortality, hepatic NF-κB activation, and plasma cytokine levels were increased in SAV rats and reduced in GTS-21-treated mice. The effects of sepsis on the GH/IGF-I system plasma IGF-I, IGF binding protein-1 (IGFBP-1), hepatic IGF-I, IGFBP-1, and GH receptor (GHR) mRNA and rhGH-responsiveness in mice were improved by GTS-21. Collectively these results confirm the protective effects of the anti-inflammatory CAP and α7nAChR activation in sepsis. They also provide evidence the CAP and α7nAChR activation could be used to attenuate hepatic GH resistance and anabolic failure in sepsis.

Are the Effects of Oral and Vaginal Contraceptives on Bone Formation in Young Women Mediated via the Growth Hormone-IGF-I Axis?

Purpose: Combined hormonal contraceptive therapy has been associated with negative bone mineral density outcomes that may be route-dependent [i.e., combined oral contraception (COC) vs. contraceptive vaginal ring (CVR)] and involve the hepatic growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis. The objective of the pilot study was to assess the impact of route of contraceptive administration on IGF-I and procollagen type I N-terminal propeptide (PINP) responses to an IGF-I Generation Test. We hypothesized that the peak rise in IGF-I and PINP concentration and area under the curve (AUC) would be attenuated following COC, but not CVR, use.Methods: Healthy, premenopausal women not taking hormonal contraception were recruited. Women were enrolled in the control group (n = 8) or randomly assigned to COC (n = 8) or CVR (n = 8) for two contraceptive cycles. IGF-I Generation Tests were used as a probe to stimulate IGF-I release and were completed during the pre-intervention and intervention phases. Serum IGF-I and PINP were measured during both IGF-I Generation Tests. The study was registered at ClinicalTrials.gov (NCT02367833).Results: Compared to the pre-intervention phase, peak IGF-I concentration in response to the IGF-I Generation Test in the intervention phase was suppressed in the COC group (p < 0.001), but not the CVR or Control groups (p > 0.090). Additionally, compared to the pre-intervention phase, PINP AUC during the intervention phase was suppressed in both COC and CVR groups (p < 0.001), while no difference was observed in the control group (p = 0.980).Conclusion: These data suggest that changes in recombinant human GH-stimulated hepatic IGF-I synthesis in response to combined hormonal contraception (CHC) use are dependent on route of CHC administration, while the influence on PINP is route-independent. Future research is needed to expand these results with larger randomized control trials in all age ranges of women who utilize hormonal contraception.Clinical Trial Registration: www.ClinicalTrials.gov registration NCT02367833.

The optimal arginine requirement in diets for juvenile humpback grouper, Cromileptes altivelis

An 8-week feeding trial was conducted to evaluate the effects of dietary arginine (Arg) levels on growth performance, gut micromorphology, oxidation resistance and immune responses of humpback grouper, Cromileptes altivelis. Seven isoenergetic (340 kcal per 100 g of dry matter), isoproteic (50% of dry matter) and isolipidic (10% of dry matter) experimental diets were formulated to contain 1.74%, 2.42%, 3.14%, 3.58%, 4.06%, 4.54% and 5.21% dietary Arg levels. Triplicate groups of 12 fish (average initial body weight: 6.55 ± 0.1 g) were fed to apparent satiation by hand twice daily (08:00 h and 16:00 h) in an indoor recirculating seawater system which was consisted of 21 glass tanks (length 60 cm × width 45 cm × height 50 cm) and mechanical and biological water filters. After the feeding trial, all remaining fish were challenged by 2.5 mg Cu(II)·L−1, and survival rates were recorded for 12 h. Results showed that weight gain% (WG%), protein efficiency ratio (PER) as well as protein productive value (PPV) of fish were improved with the increments in dietary Arg from 1.74% to 3.58%, and thereafter, values of these parameters displayed a declining trend as dietary Arg level continued to rise from 3.58% to 5.21%. Fish fed 3.14% and 3.58% dietary Arg had lower FCR and daily feed intake (DFI) than fish fed other dietary Arg levels. Quadratic regression analysis of WG% against dietary Arg levels indicated that optimal dietary Arg level for maximum growth of humpback grouper was 3.39% of dry matter (6.78% of dietary protein). Hepatosomatic index (HSI) was reduced as dietary Arg level increased. Fish fed 3.58% dietary Arg had higher whole-body protein content than fish fed other dietary Arg levels. Expression of hepatic insulin-like growth factor-I (IGF-1), target of rapamycin (TOR), S6 kinase1 (S6K1) and hypothalamus growth hormone receptor (GHR) in fish fed 3.14% and 3.58% dietary Arg was higher than that in fish fed other dietary Arg levels. Gut micromorphology was significantly influenced by dietary Arg levels. After the exposure to 2.5 mg Cu(II)·L−1 water for 12 h, fish fed 3.14% and 3.58% dietary Arg had higher survival ratios and expression of NF-E2-related factor 2 (Nrf2) and heat shock proteins genes 70 (HSP70) in head kiney. In serum, fish fed 3.58% dietary Arg had higher superoxide dismutase (SOD) and catalase (CAT) activities and immunoglobulinM (IgM) concentrations than fish fed other dietary Arg levels. In conclusion, the optimal dietary Arg requirement for maximal growth of humpback grouper was estimated to be 3.39% of dry matter (6.78% of dietary protein), and suitable dietary Arg supplementations improved growth performance, gut micromorphology, oxidation resistance as well as immunity of this species.

Effects of replacing fish meal with mussel (Cristaria plicata) meat on growth, digestive ability, antioxidant capacity and hepatic IGF-I gene expression in juvenile Ussuri catfish (Pseudobagrus ussuriensis)

An 8-week feeding trial was implemented to evaluate the effects of replacing fish meal (FM) with mussel (Cristaria plicata) meat (MM) on growth, digestive ability, antioxidant capacity and hepatic insulin-like growth factor I (IGF-I) gene expression of juvenile Ussuri catfish (Pseudobagrus ussuriensis). Three isonitrogenous and isolipidic diets were formulated to include 0, 177.5 and 355.1 g/kg of MM, accordingly, replacing 0% (M0, control), 50% (M1) and 100% (M2) of FM protein, respectively. The results showed that the final body weight, weight gain, specific growth rate and feed intake were gradually decreased with dietary MM protein levels increased, but there were no significant difference between M0 and M1 groups (p > 0.05). The protein efficiency ratio was increased significantly with dietary MM inclusion (p < 0.05). The apparent digestibility coefficient of dry matter, crude lipid and gross energy gradually increased with increasing dietary MM protein levels, but the apparent digestibility coefficient of crude protein was not significantly affected by MM protein supplementation (p > 0.05). Fish fed diet, M0 and M1 remained unaffected significantly on activities of alpha-amylase and pepsin (p > 0.05), but fish fed diet M2 had the highest activities of alpha-amylase and pepsin. Fish fed diet M1 or M2 had significantly lower hepatic total antioxidant capacity, superoxide dismutase and the higher malondialdehyde level compared to fish fed diet M0. In addition, no significant difference was observed in hepatic IGF-I gene expression level for fish fed diet M0 and diet M1, and fish fed diet M2 showed significantly lower hepatic IGF-I gene expression level. Therefore, we can conclude that MM protein can successfully substitute 50% of FM protein without significantly negative effect on growth, nutrient utilization, and hepatic IGF-I gene expression for juvenile Ussuri catfish, but the antioxidant capacity was negatively affected in the present study, what is more, the total replacement of FM by MM in diet may result in the inhibition of the growth and antioxidant capacity of fish.

Deficiency of liver-derived insulin-like growth factor-I (IGF-I) does not interfere with the skin wound healing rate.

ObjectiveIGF-I is a growth factor, which is expressed in virtually all tissues. The circulating IGF-I is however derived mainly from the liver. IGF-I promotes wound healing and its levels are decreased in wounds with low regenerative potential such as diabetic wounds. However, the contribution of circulating IGF-I to wound healing is unknown.Here we investigated the role of systemic IGF-I on wound healing rate in mice with deficiency of liver-derived IGF-I (LI-IGF-I-/- mice) during normal (normoglycemic) and impaired wound healing (diabetes).MethodsLI-IGF-I-/- mice with complete inactivation of the IGF-I gene in the hepatocytes were generated using the Cre/loxP recombination system. This resulted in a 75% reduction of circulating IGF-I. Diabetes was induced with streptozocin in both LI-IGF-I-/- and control mice. Wounds were made on the dorsum of the mice, and the wound healing rate and histology were evaluated. Serum IGF-I and GH were measured by RIA and ELISA respectively. The expression of IGF-I, IGF-II and the IGF-I receptor in the skin were evaluated by qRT-PCR. The local IGF-I protein expression in different cell types of the wounds during wound healing process was analyzed using immunohistochemistry.ResultsThe wound healing rate was similar in LI-IGF-I-/- mice to that in controls. Diabetes significantly delayed the wound healing rate in both LI-IGF-I-/- and control mice. However, no significant difference was observed between diabetic animals with normal or reduced hepatic IGF-I production. The gene expression of IGF-I, IGF-II and IGF-I receptor in skin was not different between any group of animals tested. Local IGF-I levels in the wounds were similar between of LI-IGF-I-/- and WT mice although a transient reduction of IGF-I expression in leukocytes in the wounds of LI-IGF-I-/- was observed seven days post wounding.ConclusionDeficiency in the liver-derived IGF-I does not affect wound healing in mice, neither in normoglycemic conditions nor in diabetes.

Effects of dietary soy protein concentrate meal on growth, immunity, enzyme activity and protein metabolism in relation to gene expression in large yellow croaker Larimichthys crocea

A 56-day feeding trial was conducted to investigate the effects of dietary soy protein concentrate meal (SPC) levels on growth performance, body composition, antioxidant and immune responses, enzyme activities and protein metabolism in relation to gene expression in Larimichthys crocea (initial weight 10.50±0.04g). Five isonitrogenous and isolipidic diets (45% protein and 10% lipid) were formulated by replacing 0 (the control), 25%, 50%, 75% and 100% of fish meal protein with SPC protein (designed SPC0, SPC25T, SPC50T, SPC75T and SPC100T, respectively). Lysine and methionine were added to the feed except the control diet, and the levels in the treatment diets were the same. Each diet was randomly fed twice daily (05:00 and 17:00) to apparent satiation to triplicate groups (60 fish per cage). The survival rate (SR) ranged from 90.56 to 93.89%, with no significant differences observed among dietary treatments (P>0.05). In addition, no significant differences were found for weight gain ratios (WGR), specific growth rates (SGR), feed conversion ratios (FCR) and feed intakes (FI) (P>0.05). Fish muscle protein and moisture contents did not show any statistical differences among the dietary treatments (P>0.05). Lipid contents first increased and then decreased, and the SPC25T diet was the highest. Ash contents first decreased and then increased, and the SPC100T diet was the highest. Fish whole-body composition analysis showed that with increasing dietary SPC levels, protein contents did not show any statistical differences among the dietary treatments (P>0.05). Lipid contents were significantly lower of SPC100T than SPC0 and SPC25T diets (P<0.05), and the highest was in the SPC0 diet. The contents of moisture in SPC100T diet were observed the highest, and significantly higher than the control diet (P<0.05). Ash contents of SPC50T diet were significant higher than SPC0 and SPC25T diets (P<0.05), but no significant differences were found among the diets of SPC50T, SPC75T and SPC100T (P>0.05). Significantly lower liver total superoxide dismutase (t-SOD) activity was found for the SPC100T diet than the SPC25T and SPC50T diets (P<0.05). There were no significant differences among the dietary diets with regard to malondialdehyde (MDA), catalase (CAT), and glutathione peroxidase （GPx） (P>0.05). Serum lysozyme (LYZ) activity was significantly lower in the SPC100T diet than in the SPC25T and SPC75T diets (P<0.05). There were no significant differences among the diets for alkaline phosphatase (AKP), complement C3 and C4 (P>0.05). Regarding digestive enzymes, no significant differences were found for hintgut alpha-amylase and lipase activity between the dietary treatments and the control diet (P>0.05). Among all diets, trypsin activity was the highest in fish fed the SPC75 diet, and significantly higher than SPC50T (P<0.05), but there were no significant differences among the SPC0, SPC25T, SPC75T and SPC100T diets (P>0.05). For liver protein metabolism enzymes, no significant differences were found in alanine aminotransferase (ALT) and aspartate amino-transferase (AST) among all dietary diets (P>0. 05). With increasing dietary SPC levels, hepatic insulin-like growth factor-I (IGF-I) expression decreased, and significant differences were observed between SPC50T, SPC75T, SPC100T and the control diets (P<0.05). Target of rapamycin (TOR) expression in the liver decreased, and there were significant differences between the treatment and the control diets (P<0.05).In conclusion, the results of this study suggest that SPC can completely replace fish meal protein as feed for large yellow croaker with no significant negative effects on growth performance.

Effects of dietary amino acid patterns on growth, feed utilization and hepatic IGF-I, TOR gene expression levels of hybrid grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂) juveniles

A 7-week growth trial was conducted to evaluate effects of dietary amino acid patterns on growth, feed utilization and hepatic IGF-I, TOR genes expression levels of hybrid grouper (Epinephelus fuscoguttatus ♀×Epinephelus lanceolatus ♂) juveniles. Four isoenergetic (350kcal per 100g dry matter), isoproteic (53.5% of dry matter) and isolipidic (7% of dry matter) experimental diets were formulated with crystalline-amino acids (AAs) replacing approximately 42% fishmeal protein-bound nitrogen to keep dietary AA patterns in line with the overall AA patterns of whole-egg protein (WEPAA), whole-body protein (WBPAA), muscle protein (MCPAA) of hybrid grouper and fishmeal (anchovy) protein (FMPAA), respectively. Each experimental diet was fed to triplicate groups of 15 hybrid grouper juveniles (average initial weight of 10.8g/fish) which were stocked into small floating cages (L 120cm×W 70cm×H 50cm). Experimental cages were labeled and located in four connective 6-m3 indoor concrete tanks (L 3m×W 2m×H 1m) with 3 cages occurring in each tank.Weight gain (WG) of fish fed the FMPAA diet was significantly (P<0.05) higher than that of fish fed the WEPAA diet or the WBPAA diet but did not significantly differ (P≥0.05) from that of fish fed the MCPAA diet. Values of daily feed intake (DFI) of fish fed the WEPAA diet or the WBPAA diet was significantly higher than that of fish fed the MCPAA diet or the FMPAA diet. Fish fed the FMPAA diet had significantly lower feed conversion ratios (FCRs), higher protein efficiency ratio (PER) and higher protein productive value (PPV) compared to fish fed other experimental diets. Whole-body protein content of fish fed the FMPAA diet was significantly higher than that of fish fed the WEPAA diet or the WBPAA diet. Muscle amino acid compositions were influenced by dietary amino acid pattern. Plasma total protein (TP) concentration of fish fed the FMPAA diet was significantly higher than that of fish fed the WEPAA diet or the WBPAA diet. The relative mRNA expression levels of insulin like growth factor-I (IGF-I) gene in liver of fish fed the FMPAA diet and the MCPAA diet were significantly higher than those of fish fed the WEPAA diet and the WBPAA diet. Fish fed the FMPAA diet showed significantly higher hepatic target of rapamycin (TOR) gene expression level than fish fed other experimental diets. Results of this study indicated that the amino acid pattern of fishmeal (anchovy) protein was more suitable as a reference amino acid pattern in diets of juvenile hybrid grouper compared to the amino acid pattern of whole-egg protein, whole-body protein or muscle protein of this fish species.

Dietary vitamin B12 requirement of fingerling blunt snout bream Megalobrama amblycephala determined by growth performance, digestive and absorptive capability and status of the GH-IGF-I axis

This study aimed to investigate the optimal dietary vitamin B12 requirement of fingerling blunt snout bream Megalobrama amblycephala based on the results of growth performance, intestinal digestive and absorptive capability and responses of the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis. Fish (initial body weight: 0.71±0.03g) were randomly assigned to six purified diets containing graded levels of vitamin B12 (0, 0.028, 0.051, 0.12, 0.23 and 0.41mg/kg) for 12weeks. Both weight gain (WG) and specific growth rate increased significantly (P<0.05) as dietary vitamin B12 levels increased from 0 to 0.051mg/kg, then plateaued with further increasing levels. Feed conversion ratio decreased as dietary vitamin B12 levels increased from 0 to 0.12mg/kg, but no statistical difference was observed. Whole-body composition and intestinal brush border enzymes activities also exerted little difference within the vitamin B12 range tested, whereas hepatic vitamin B12 contents increased remarkably (P<0.01) with increasing dietary vitamin B12 levels. Intestinal protease, amylase and lipase activities all increased significantly (P<0.05) as dietary vitamin B12 levels increased from 0 to 0.12mg/kg, but decreased remarkably (P<0.05) with further increasing vitamin B12 levels. Similar results were also observed in hepatic IGF-I expressions. Furthermore, the mRNA expressions of GH in the brain decreased significantly (P<0.05) with increasing dietary vitamin B12 levels. Based on the broken-line regression analysis of WG, the optimal dietary vitamin B12 requirement of fingerling blunt snout bream was estimated to be 0.06mg/kg. In addition, a supplementation of 0.12mg/kg vitamin B12 boosted intestinal digestive capability and hepatic IGF-I expression. Statement of relevanceThis study investigated the optimal dietary vitamin B12 requirement of fingerling blunt snout bream based on growth performance. The underlying mechanisms were also investigated with emphasis on intestinal digestive and absorptive capability and modulation of the GH-IGF-I axis. Data obtained here might facilitate the development of low-cost formulated feed for aquatic species.

Differential responses of the somatotropic and thyroid axes to environmental temperature changes in the green iguana

Growth hormone (GH), together with thyroid hormones (TH), regulates growth and development, and has critical effects on vertebrate metabolism. In ectotherms, these physiological processes are strongly influenced by environmental temperature. In reptiles, however, little is known about the direct influences of this factor on the somatotropic and thyroid axes. Therefore, the aim of this study was to describe the effects of both acute (48h) and chronic (2weeks) exposure to sub-optimal temperatures (25 and 18°C) upon somatotropic and thyroid axis function of the green iguana, in comparison to the control temperature (30–35°C). We found a significant increase in GH release (2.0-fold at 25°C and 1.9-fold at 18°C) and GH mRNA expression (up to 3.7-fold), mainly under chronic exposure conditions. The serum concentration of insulin-like growth factor-I (IGF-I) was significantly greater after chronic exposure (18.5±2.3 at 25°C; 15.92±3.4 at 18°C; vs. 9.3±1.21ng/ml at 35°C), while hepatic IGF-I mRNA expression increased up to 6.8-fold. Somatotropic axis may be regulated, under acute conditions, by thyrotropin-releasing hormone (TRH) that significantly increased its hypothalamic concentration (1.45 times) and mRNA expression (0.9-fold above control), respectively; and somatostatin (mRNA expression increased 1.0–1.2 times above control); and under chronic treatment, by pituitary adenylate cyclase-activating peptide (PACAP mRNA expression was increased from 0.4 to 0.6 times). Also, it was shown that, under control conditions, injection of TRH stimulated a significant increase in circulating GH. On the other hand, while there was a significant rise in the hypothalamic content of TRH and its mRNA expression, this hormone did not appear to influence the thyroid axis activity, which showed a severe diminution in all conditions of cold exposure, as indicated by the decreases in thyrotropin (TSH) mRNA expression (up to one-eight of the control), serum T4 (from 11.6±1.09 to 5.3±0.58ng/ml, after 2weeks at 18°C) and T3 (from 0.87±0.09 to 0.05±0.01ng/ml, under chronic conditions at 25°C), and Type-2 deiodinase (D2) activity (from 992.5±224 to 213.6±26.4fmolI125T4/mgh). The reduction in thyroid activity correlates with the down-regulation of metabolism as suggested by the decrease in the serum glucose and free fatty acid levels. These changes apparently were independent of a possible stress response, at least under acute exposure to both temperatures and in chronic treatment to 25°C, since serum corticosterone had no significant changes in these conditions, while at chronic 18°C exposure, a slight increase (0.38 times above control) was found. Thus, these data suggest that the reptilian somatotropic and thyroid axes have differential responses to cold exposure, and that GH and TRH may play important roles associated to adaptation mechanisms that support temperature acclimation in the green iguana.

Cysteine induces longitudinal bone growth in mice by upregulating IGF-I.

Cysteine (Cys) is known to exert various effects, such as antioxidant, antipancreatitic and antidiabetic effects. However, the effects of Cys on longitudinal bone growth have not been elucidate to date. Thus, the aim of the present study was to evaluate the effects of Cys on bone growth. Growth-plate thickness and bone parameters, such as bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), connectivity density (Conn.D) and total porosity were analyzed by means of micro-computed tomography (μCT). The levels of serum insulin-like growth factor-I (IGF-I) were measured by enzyme-linked immunosorbent assay (ELISA). Hepatic IGF-I mRNA expression was analyzed by quantitative polymerase chain reaction (qPCR). The phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) was investigated by western blot analysis. Our results revealed that Cys increased IGF-I mRNA expression in HepG2 cells. The thickness of the growth plates was increased following treatment with Cys. Moreover, BV/TV, Tb.Th, TbN, Conn.D and total porosity were improved following treatment with Cys. Hepatic IGF-I mRNA expression and serum IGF-I levels were increased by Cys. The levels of phosphorylated JAK2 and STAT5 were elevated by Cys. The findings of our study indicate that Cys increases the thickness of growth plates through the upregulation of IGF-I, which results from the phosphorylation of JAK2-STAT5. Thus, our data suggest that Cys may have potential for use as a growth-promoting agent.

In Ovo Administration of Silver Nanoparticles and/or Amino Acids Influence Metabolism and Immune Gene Expression in Chicken Embryos

Due to their physicochemical and biological properties, silver nanoparticles (NanoAg) have a wide range of applications. In the present study, their roles as a carrier of nutrients and an immunomodulator were tested in chicken embryos. Cysteine (Cys)+NanoAg injected embryos had smaller livers but heavier breasts on the 19th day of embryogenesis. Cys injected embryos had lower oxygen consumption compared to threonine (Thr) or NanoAg injected embryos. The energy expenditure in Thr+NanoAg, or NanoAg injected embryos was higher than Cys or Cys+NanoAg but was not different from uninjected control embryos. Relative expression of the hepatic insulin-like growth factor-I (IGF-I) gene was higher in Cys or NanoAg injected embryos after lipopolysaccharide (LPS) induction. The gene expression of hepatic tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) did not differ among amino acids, NanoAg and uninjected controls in the non-LPS groups, but increased by many folds in the LPS treated NanoAg, Cys and Cys+NanoAg groups. In LPS treated spleens, TNF-α expression was also up-regulated by NanoAg, amino acids and their combinations, but interleukin-10 (IL-10) expression was down-regulated in Thr, Cys or Thr+NanoAg injected embryos. Toll like receptor-2 (TLR2) expression did not differ in NanoAg or amino acids injected embryos; however, toll like receptor-4 (TLR4) expression was higher in all treated embryos, except for Cys+NanoAg, than in uninjected control embryos. We concluded that NanoAg either alone or in combination with amino acids did not affect embryonic growth but improved immunocompetence, indicating that NanoAg and amino acid complexes can act as potential agents for the enhancement of innate and adaptive immunity in chicken.

The somatotropic axis during the physiological estrus cycle in dairy heifers—Effect on hepatic expression of GHR and SOCS2

Pituitary growth hormone (GH) release and hepatic insulin-like growth factor-I (IGF-I) production increase after an injection of 17β-estradiol (E2) in ovariectomized dairy cattle. However, whether endogenous sexual steroid hormones also influence the hepatic GH receptor (GHR) signaling pathway during a physiological estrus cycle remains unclear. The aim of this study was to analyze the hepatic GHR signaling pathway during the luteal phase and after a period of increased E2 concentrations (after ovulation) as well as in 7 heifers before ovulation. Ovarian ultrasounds were performed daily during repeated physiological cycles (n=56) of 30 Holstein Friesian heifers to determine ovulation [before ovulation (n=7, bOv) and after ovulation 24–60h after the appearance of estrus signs (n=49, aOv)] and luteal phase (CLP; d 12±1 after ovulation). Blood samples and liver biopsies were obtained, and blood concentrations of E2, P4, insulin-like growth factor (IGF)-I, IGF-II, and GH were measured. In the liver biopsies, we determined mRNA expression of the estrogen receptor α (ERα), GHR, Janus kinase 2 (JAK2), signal transducer and activator of transcription 5B (STAT5B), suppressor of cytokine signaling (SOCS)2 and 3, IGF-I, and IGF-II by quantitative reverse transcription-PCR. The concentration of E2 was higher bOv than aOv and CLP, as expected. The concentrations of IGF-I and GH were higher bOv and aOv compared with CLP. In contrast, concentrations of IGF-II were lower aOv compared with bOv and CLP. The mRNA expression of GHR was higher in liver biopsies obtained bOv compared with aOv and CLP. Notably, the expression of SOCS2 was higher bOv than aOv and in the CLP. Increased hepatic expression of SOCS2 during estrus was detectable when IGF-I concentrations were high; this result might indicate that SOCS2 expression attenuates the GHR signal transduction pathway during the phase of increased pituitary GH release. In conclusion, hepatic GHR and SOCS2 mRNA expression appeared to be promptly and sensitively regulated by increased E2 levels before ovulation of dairy heifers.

Acclimation to different environmental salinities induces molecular endocrine changes in the GH/IGF-I axis of juvenile gilthead sea bream (Sparus aurata L.).

To assess the role of the GH/IGF-I axis in osmotic acclimation of the gilthead seabream Sparus aurata, juvenile specimens were acclimated to four environmental salinities: hyposmotic (5 ‰), isosmotic (12 ‰) and hyperosmotic (40 and 55 ‰). The full-length cDNAs for both pituitary adenylate cyclase-activating peptide (PACAP) and prepro-somatostatin-I (PSS-I), the precursor for mature somatostatin-I (SS-I), were cloned. Hypothalamic PACAP and PSS-I, hypophyseal growth hormone (GH) and prolactin (PRL), and hepatic insulin-like growth factor-I (IGF-I) mRNA expression levels were analyzed in the four rearing salinities tested. PACAP and IGF-I mRNA values increased significantly in response to both 5 and 55 ‰ salinities, showing a U-shaped curve relationship with the basal level in the 40 ‰ group. Hypothalamic PSS-I expression increased strongly in the 55 ‰ environment. GH mRNA levels did not change in any of the tested environmental salinities. PRL mRNA maximum levels were encountered in the 5 and 12 ‰ environments, but significantly down-regulated in the 40 ‰. Plasma cortisol levels significantly increased in the 40 ‰ environment. These results are discussed in relation to the well-known high adaptability of Sparus aurata to different environmental salinities and the role of the GH/IGF-I axis in this process.

Effect of KH-BaRoKer-SeongJangTang based on traditional medicine theory on longitudinal bone growth

KH-BaRoKer-SeongJangTang (KBS) is a recently developed formulation by using traditional drugs considering traditional medical theory of Oriental books such as ShinNongBonChoGyeong and JuRye, which has been used to improve the growth of child in Korea. Although KBS is usually prescribed to many children who are in retard for their age, its pharmacological effects have not been fully understood in experimental models. The aim of this study was to evaluate the effects of KBS on bone growth. Growth plate thickness and bone parameters such as bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), connection density (Conn.D), and total porosity were analyzed by means of microcomputed tomography. Serum insulin-like growth factor-I (IGF-I) levels were measured by enzyme-linked immunosorbent assay. Hepatic IGF-I mRNA expression was analyzed by real-time polymerase chain reaction. Phosphorylation of signal transducer and activator of transcription5 (STAT5) was investigated using Western blot analysis and immunohistochemistry. The thickness of growth plate was increased by KBS. BV/TV, Tb.Th, TbN, Conn.D, and total porosity were improved by KBS. Hepatic IGF-I mRNA and serum IGF-I levels were elevated by KBS. Phosphorylation of STAT5 was increased with administration of KBS. These results suggest that KBS would be helpful to children who are in retard for their age through the elevation of IGF-I.

Melatonin and Peripheral Circuitries: Insights on Appetite and Metabolism in Danio Rerio

Melatonin is a neuroendocrine transducer of circadian/circannual rhythms able to synchronize organism's physiological activity. On the basis of our recent findings on appetite regulation by melatonin in the zebrafish brain, the aim of this study was to evaluate melatonin's role in peripheral circuitries regulating food intake, growth, and lipid metabolism. For this purpose, the effect of two melatonin doses (100 nM and 1 μM) administered for 10 days, via water, to adult zebrafish was evaluated at both physiological and molecular levels. The major signals controlling energy homeostasis were analyzed together. Additionally, the effect of melatonin doses on muscle metabolic resources was evaluated. The results obtained indicate that melatonin reduces food intake by stimulating molecules involved in appetite inhibition, such as leptin (LPT), in the liver and intestine and MC4R, a melanocortin system receptor, in the liver. Moreover, melatonin decreases hepatic insulin-like growth factor-I (IGF-I) gene expression, involved in growth process and other signals involved in lipid metabolism such as proliferator-activated receptors (PPARα, β, and γ) and sterol regulatory element-binding protein (SREBP). These results were correlated with lower levels of lipids in the muscles as evidenced by the macromolecular pools analyses. The findings obtained in this study could be of great interest for a better understanding of the molecular mechanisms as the basis of food intake control and, in turn, can be a useful tool for medical and aquaculture applications.

Divergence between hepatic insulin-like growth factor (IGF)-I mRNA expression and IGF-I serum levels in Leishmania (Leishmania) infantum chagasi-infected dogs

Visceral leishmaniasis (VL) caused in the New World by Leishmania (Leishmania) infantum chagasi has dog as important peridomestic reservoir in its transmission cycle. Since VL in infected animals is similar to human VL, its study is interesting for human pathology. During Leishmania infection, insulin-like growth factor-I (IGF-I) plays a role in the host-parasite interaction, favoring parasite growth, particularly acting directly on Leishmania. We evaluated IGF-I mRNA expression in different organs/tissues, which was differently modulated in dogs naturally infected by L. (L.) infantum chagasi. We also evaluated the hepatic IGF-I mRNA and serum IGF-I levels in infected dogs. Hepatic mRNA IGF-I expression was higher in the infected dogs than in control animals. However, the serum levels of IGF-I, which are related to the production of this factor in the liver, were reduced in the infected dogs compared with the non-infected controls. Thus, we suggest interference in post-transcriptional processing in IGF-I production in active visceral leishmaniasis.

Effects of dietary rapeseed meal on growth performance, digestion and protein metabolism in relation to gene expression of juvenile cobia (Rachycentron canadum)

A 60-day feeding trial in seawater floating cages (1.5×1.5×2.5m) was conducted to investigate the effects of dietary rapeseed meal (RM) levels on feed intake, growth, survival, digestion and protein metabolism in relation to gene expression of juvenile cobia (initial body weight 94.6g). Five isonitrogenous (crude protein 450gkg−1 of dry matter) and isoenergetic (20kJg−1) practical diets were formulated by replacing 0 (the control), 125, 250, 375 and 500gkg−1 fish meal protein with RM protein. Each diet was randomly fed to triplicate groups of fish, and each cage was stocked with 20 fish. Fish were fed twice daily (06:00 and 18:00) to apparent satiation. The survival ranged from 96.7 to 98.3%, and no significant difference was observed among dietary treatments (P>0.05). With increasing dietary RM levels, feed intake (FI), specific growth rate (SGR) and feed efficiency (FE) decreased. Fish fed the diet with 250gkg−1 or more protein from RM had significantly lower SGR and FE than the control group (P<0.05), but there was no significant difference in FI at this level compared with the control group (P>0.05). Apparent digestibility coefficients (ADCs) of dry matter (DM), crude protein and energy significantly decreased with increasing dietary RM levels (P<0.05). Fish fed the diet with 250gkg−1 or more protein from RM had significantly lower ADC values of crude protein and energy compared with the control group (P<0.05). Whole-body crude protein and crude lipid decreased with increasing dietary RM levels. Fish fed the diet with 500gkg−1 protein from RM had significantly lower whole-body crude protein and crude lipid compared with the control group (P<0.05). However, whole-body moisture and ash showed opposite trends with crude protein and crude lipid. Moisture, crude protein and crude lipid contents in cobia muscle showed similar trends with those in whole body. There were no significant differences in plasma ammonia, urea, cholesterol and amino acids among fish fed the experimental diets (P>0.05). Fish fed the diet with 500gkg−1 protein from RM had significantly lower aspartate aminotransferase (AST) activity in liver than the control group (P<0.05). Hepatic insulin-like growth factor I (IGF-I) gene expression level was significantly decreased in fish fed the diet with 500gkg−1 protein from RM compared with the control group (P<0.05). However, IGF-I gene expression level in dorsal muscle was significantly increased in fish fed this diet compared with the control group (P<0.05). No significant differences were observed in target of rapamycin (TOR) expression levels in cobia liver and dorsal muscle at different RM levels (P>0.05). Results of the present study indicated that protein from RM could substitute 125gkg−1 fish meal protein without influencing the growth, feed utilization and protein metabolism in cobia. The higher substitution levels of RM induced negative influences on feed intake, growth and hepatic IGF-I expression level.