Liver IGF-I mRNA Research Articles

Effects of starter feeding and early weaning on developmental expressions of IGF-I gene in liver and IGF-IR gene in rumen of lambs from birth to eighty-four days of age

The early weaning and starter feeding have significant effects on lamb growth and digestive tract development. However, it is not clear whether the expression of IGF-1/IGF-1R genes could be affected by feeding starter and weaning. Therefore, a total of 102 Hu male neonatal lambs were randomly divided into 3 groups: fed with starter at 42d + weaned at 56d (group A), fed with starter at 7d + weaned at 28d (group B) and fed with starter at 7d + weaned at 56d (group C), to explore the effects of starter feeding and weaning age on developmental expressions of IGF-I gene in liver and IGF-IR gene in rumen of Hu sheep. The results showed that IGF-I and IGF-IR genes were expressed extensively in various tissues of lambs, the expression of IGF-I was significantly higher in liver (p < 0.01), while the expression of IGF-IR was higher in rumen among gastrointestinal tissues. The mRNA level of IGF-I of group C was strikingly higher than that of group A at 28, 70, and 84d (p < 0.01) in liver, respectively. Rumen mRNA level of IGF-IR of group C was prominently higher than that of group A at 70d and 84d (p < 0.05), respectively. However, IGF-IR expression of group A was higher than that of group C at 14 and 42d (p < 0.05). The mRNA level of IGF-I of group B was significantly higher than that of group C at 42, 56, 70, and 84d (p < 0.01) in liver, while IGF-IR expression of group B was higher than that of group C at 70d (p < 0.01). In conclusion, early weaning and starter feeding affected liver IGF-I mRNA and rumen IGF-IR mRNA expression.

Inclusion level of deoiled rice bran (DORB) in the diet of Labeo rohita (Hamilton, 1882) fingerlings: Effect on growth and gene expression of IGF-I and IGF-II

A 60-day feeding trial was conducted to evaluate the effect of deoiled rice bran (DORB) on the growth performance and liver IGF-I and IGF-II mRNA expression in a freshwater fish, Labeo rohita. Six isonitrogenous (30%), isolipidic (6%) and iso-energetic (1.8MJ/100g) diets were prepared with different inclusion level of DORB viz., C (control, 0%), T20 (20%), T30 (30%), T40 (40%), T50 (50%) and T60 (60%). Three hundred and fifteen (315) fingerlings with 15 fish per tank having an average weight of 8.0±0.5g were randomly distributed in seven treatments in triplicates following a completely randomized design. At the end of the experiment, growth and nutrient utilization were evaluated in terms of weight gain% (WG %), SGR, FCR, PER, RNA/DNA ratio along with the gene expression of IGF-I and IGF-II. The weight gain % and specific growth rate were similar in 30, 40, 50 and 60% DORB fed groups, but higher (p<0.05) than the control and commercial diet fed groups. The PER (Protein Efficiency Ratio), LER (Lipid Efficiency Ratio) and FCR (Feed Conversion Ratio) were similar (p>0.05) in 30, 40, 50 and 60% DORB fed groups. The RNA-DNA ratio was significantly lower in T50 group, which was similar to T60 group. Based on second order polynomial regression analysis (y=−0.008x2+0.5227x+1.3407, R2=0.91), the expression of IGF-I was found to be maximum at 33% inclusion level. The hepatic IGF-I and IGF-II gene expression were checked using real time PCR normalised against the β-actin gene and found to be maximum at the dietary inclusion level of 33%. Hence, from these results it can be concluded that though growth rate was similar in all the groups fed with DORB at 30 to 60% of inclusion level, but an optimum inclusion level of DORB at 33% is best to support the nutrient utilization and growth performance of Labeo rohita fingerlings based on gene expression of IGFI and IGF II in liver.

Insulin injection restored increased insulin receptor substrate (IRS)-2 protein during short-term protein restriction but did not affect reduced insulin-like growth factor (IGF)-I mRNA or increased triglyceride accumulation in the liver of rats.

Dietary protein restriction reduces insulin-like growth factor (IGF)-I synthesis and impairs growth. Moreover, insulin secretion is impaired and hepatic insulin signaling is activated presumably through upregulation of insulin receptor substrate (IRS)-2, which can stimulate lipogenesis thereby resulting in steatosis. In order to determine whether impaired insulin secretion is the primary cause of these changes, we injected insulin into protein-restricted rats and compensated for the reduction in insulin secretion for 1 and 7 d. Insulin infusion did not overcome the reduction in liver IGF-I mRNA nor the hepatic triglyceride accumulation. In contrast, it clearly suppressed the upregulation of hepatic IRS-2 on day 1, but not on day 7. Furthermore, insulin elimination increased IRS-2 in H4IIE-C3 cells. In summary, we found that reduced insulin secretion during protein restriction directly increased hepatic IRS-2 as a rapid response on day 1, while additional mechanisms contributed to the upregulation of IRS-2 on day 7.

Effect of low molecular weight fish protein hydrolysate on growth performance and IGF-I expression in Japanese flounder (Paralichthys olivaceus) fed high plant protein diets

Seven isonitrogenous and isoenergetic experimental diets were formulated to investigate the effect of low molecular weight fish protein hydrolysate (FPH) in diets on growth performance, feed utilization and liver IGF-I mRNA levels in Japanese flounder (38.80 ± 1.11 g) fed with high plant protein diets. Fish meal protein was, respectively, replaced by 6% (FPH6), 11% (FPH11), 16% (FPH16), 21% (FPH21), 26% (FPH26) FPH of total dietary protein. FPH diets contained a constant high level of plant protein (690 g kg−1) from soybean meal. As a positive control diet, FM2 contained about 590 g kg−1 plant protein and 410 g kg−1 fish meal protein, while negative control diet FM1 contained about 690 g kg−1 plant protein and 310 g kg−1 fish meal protein. The expression levels of liver IGF-I mRNA were evaluated using real-time PCR normalized against the 18S rRNA gene. The results showed that moderate low molecular weight FPH (FPH11) improved growth performance and protein retention. Fish fed with FPH11 and control diet FM2 had similar growth and feed utilization, while high-level low molecular weight FPH did not improve growth performance and protein retention, and depressed liver IGF-I mRNA expression in Japanese flounder.

Insulin-Like Growth Factor-I, Inflammatory Proteins, and Fibrosis in Subjects With Nonalcoholic Fatty Liver Disease

Inflammation may have a pathogenic role in the progression of nonalcoholic fatty liver disease (NAFLD); by contrast, the role of anti-inflammatory molecules has not been addressed. Low circulating levels of the anti-inflammatory molecule IGF-I have been described in subjects with NAFLD. The aim of the study was to elucidate the clinical significance of IGF-I in NAFLD and its relationship with inflammatory biomarkers and fibrosis. We conducted a cross-sectional study and in vitro experiments on hepatic HepG2 cells at the Internal Medicine and Gastrointestinal and Liver Units of the Universities of Catanzaro and Palermo. A total of 221 individuals with NAFLD diagnosed on ultrasonography (cohort 1) and 50 subjects with biopsy-proven NAFLD (cohort 2) participated in the study. Liver ultrasonography was performed on cohort 1, and hepatic biopsies were obtained from cohort 2. NAFLD fibrosis and Kleiner scores were calculated. IGF-I and inflammatory biomarker plasma concentrations were assessed with specific assays. In the in vitro study, real-time RT-PCR was used to assess the mRNA expression levels of acute-phase reactants. In the first cohort, circulating IGF-I levels showed an inverse correlation with NAFLD fibrosis score and inflammatory biomarkers; similarly in the second cohort, liver IGF-I mRNA levels and the fibrosis score showed a negative relationship. Finally, we showed that IGF-I was able to directly modulate the expression of acute-phase reactants, decreasing C-reactive protein and fibrinogen levels and up-regulating albumin expression in HepG2 cells. The present data suggest that evaluation of circulating IGF-I and proinflammatory markers might be useful to assess comprehensively the severity of the disease in individuals with NAFLD.

Effects of dietary arginine levels and carbohydrate-to-lipid ratios on mRNA expression of growth-related hormones in largemouth bass, Micropterus salmoides

Utilizing the tissue samples and growth data collected from our two preceding researches in largemouth bass (LMB), we have investigated effects of dietary arginine (Arg) levels and carbohydrate-to-lipid (CHO/LIP) ratios on the GH, IGF-I and insulin expression in related tissues to find possible relationships between the nutrient intake, growth performance and transcript level. Hepatic IGF-I and pituitary GH mRNA levels were significantly up-regulated by lower dietary Arg levels from 1.94% to 3.01% and by higher levels from 2.76% to 3.01%, respectively, while Brockmann body (BB)-containing tissue insulin mRNA expression was not affected. Dietary CHO/LIP ratios ranging from 0.32 to 5.17 (w/w) affected pituitary GH, liver IGF-I and BB-containing tissue insulin mRNA expression in a ratio-specific pattern. The lower ratios from 0.32 to 2.36 significantly up-regulated GH and insulin transcript levels, but significantly down-regulated IGF-I transcript levels; the higher ratios did no longer exert any further effects on them. Meanwhile, two strong positive correlations (r=0.892, r=0.885) between hepatic IGF-I transcript levels and specific growth rates of tested fish were observed with varying dietary Arg levels and CHO/LIP ratios, respectively. These findings indicate that in LMB dietary Arg levels and CHO/LIP ratios regulate differentially the endocrine system of GH, IGF-I and insulin at transcription level; this system, in turn, plays a fundamental role in the regulation of the nutrient metabolism and somatic growth; and that hepatic IGF-I mRNA abundance should be a more reliable index to assess growth and nutritional fitness than the others, at least in LMB.

Growth and endocrine effects of recombinant bovine growth hormone treatment in non-transgenic and growth hormone transgenic coho salmon

To examine the relative growth, endocrine, and gene expression effects of growth hormone (GH) transgenesis vs. GH protein treatment, wild-type non-transgenic and GH transgenic coho salmon were treated with a sustained-release formulation of recombinant bovine GH (bGH; Posilac™). Fish size, specific growth rate (SGR), and condition factor (CF) were monitored for 14weeks, after which endocrine parameters were measured. Transgenic fish had much higher growth, SGR and CF than non-transgenic fish, and bGH injection significantly increased weight and SGR in non-transgenic but not transgenic fish. Plasma salmon GH concentrations decreased with bGH treatment in non-transgenic but not in transgenic fish where levels were similar to controls. Higher GH mRNA levels were detected in transgenic muscle and liver but no differences were observed in GH receptor (GHR) mRNA levels. In non-transgenic pituitary, GH and GHR mRNA levels per mg pituitary decreased with bGH dose to levels seen in transgenic salmon. Plasma IGF-I was elevated with bGH dose only in non-transgenic fish, while transgenic fish maintained an elevated level of IGF-I with or without bGH treatment. A similar trend was seen for liver IGF-I mRNA levels. Thus, bGH treatment increased fish growth and influenced feedback on endocrine parameters in non-transgenic but not in transgenic fish. A lack of further growth stimulation of GH transgenic fish suggests that these fish are experiencing maximal growth stimulation via GH pathways.

Short-term growth hormone or IGF-I administration improves the IGF-IGFBP system in arthritic rats

ObjectiveAdjuvant-induced arthritis is an experimental model of rheumatoid arthritis that inhibits the GH-IGF-I axis and decreases body weight gain and muscle mass. Although chronic GH or IGF-I treatment increases body weight gain in arthritic rats, muscle resistance to GH and IGF-I is a very common complication in inflammatory diseases. In this study we examine the effect of short-term administration of rhGH and rhIGF-I on liver and muscle IGF-I, IGFBP-3 and −5 as well as on the ubiquitin-ligases MuRF1 and atrogin-1 in the muscle of arthritic rats. DesignArthritis was induced in adult male Wistar rats by an intradermal injection of 4mg of Freund's adjuvant. Fifteen days after adjuvant injection, 300μg/kg of rhGH or 200μg/kg of rhIGF or saline was administrated 18 and 3h before decapitation. A pair-fed group injected with saline was included in order to discard a possible effect of decreased food intake. Gene expression of IGF-I, GHR, IGFBP-3, IGFBP-5, atrogin-1 and MuRF1 were quantified using RT-PCR. In serum, IGF-I was measured by radioimmunoassay (RIA) and IGFBP-3 by ligand blot. ResultsArthritis decreased serum IGF-I and IGF mRNA in liver (P<0.05), but not in skeletal muscle. In arthritic rats, rhGH increased serum IGF-I and liver IGF-I mRNA similar to the levels of pair-fed rats. Arthritis increased atrogin-1, MuRF1, IGFBP-3 and IGFBP-5 mRNA in muscle (P<0.01). IGFBP-3 mRNA was downregulated by rhIGF-I, but not by rhGH, administration in control and arthritic rats (P<0.05). Administration of rhGH and rhIGF-I increased IGFBP-5 in the gastrocnemius of arthritic rats. ConclusionsShort-term rhGH and rhIGF-I administration was found to increase muscle IGFBP-5 mRNA, whereas only rhIGF-I administration decreased muscle IGFBP-3 mRNA in control and arthritic rats. These data suggest that arthritis does not induce GH or IGF-I resistance in skeletal muscle.

Growth hormone (GH) treatment acts on the endocrine and autocrine/paracrine GH/IGF-axis and on TNF-α expression in bony fish pituitary and immune organs

There exist indications that the growth hormone (GH)/insulin-like growth factor (IGF) axis may play a role in fish immune regulation, and that interactions occur via tumour necrosis factor (TNF)-α at least in mammals, but no systematic data exist on potential changes in GH, IGF-I, IGF-II, GH receptor (GHR) and TNF-α expression after GH treatment. Thus, we investigated in the Nile tilapia the influence of GH injections by real-time qPCR at different levels of the GH/IGF-axis (brain, pituitary, peripheral organs) with special emphasis on the immune organs head kidney and spleen. Endocrine IGF-I served as positive control for GH treatment efficiency. Basal TNF-α gene expression was detected in all organs investigated with the expression being most pronounced in brain. Two consecutive intraperitoneal injections of bream GH elevated liver IGF-I mRNA and plasma IGF-I concentration. Also liver IGF-II mRNA and TNF-α were increased while the GHR was downregulated. In brain, no change occurred in the expression levels of all genes investigated. GH gene expression was exclusively detected in the pituitary where the GH injections elevated both GH and IGF-I gene expression. In the head kidney, GH upregulated IGF-I mRNA to an even higher extent than liver IGF-I while IGF-II and GHR gene expressions were not affected. Also in the spleen, no change occurred in GHR mRNA, however, IGF-I and IGF-II mRNAs were increased. In correlation, in situ hybridisation showed a markedly higher amount of IGF-I mRNA in head kidney and spleen after GH injection. In both immune tissues, TNF-α gene expression showed a trend to decrease after GH treatment. The stimulation of IGF-I and also partially of IGF-II expression in the fish immune organs by GH indicates a local role of the IGFs in immune organ regulation while the differential changes in TNF-α support the in mammals postulated interactions with the GH/IGF-axis which demand for further investigations.

Skeletal muscle catabolism in trinitrobenzene sulfonic acid–induced murine colitis

The present study determined whether the muscle atrophy produced by colitis is associated with altered rates of muscle protein synthesis or degradation, as well as the potential role of the local (eg, muscle) insulin-like growth factor (IGF) system and muscle-specific ubiquitin E3 ligases atrogin-1 and MuRF1 in mediating altered muscle protein balance. Colitis was induced in C57BL/6 mice by intrarectal administration of trinitrobenzene sulfonic acid (TNBS), and blood and tissues were collected on day 10. Mice with inflammatory bowel disease demonstrated reduced skeletal muscle mass and protein content, whereas colonic segment weight and gross damage score were both increased in mice with colitis, compared with time-matched control values. There was no change in muscle protein synthesis in mice with inflammatory bowel disease; but there was an increased protein breakdown (45%), proteasome activity (85%), and messenger RNA (mRNA) expression for atrogin-1 and MuRF1 (200%-300%) in muscle. These changes were associated with a reduction in liver (but not muscle) IGF-I mRNA as well as a reduction in both total and free IGF-I in the blood. Colitis decreased the hepatic content of IGF binding protein (IGFBP)–3 mRNA by 40% and increased IGFBP-1 mRNA by 100%. In contrast, colitis did alter IGFBP mRNAs in muscle. The tumor necrosis factor– α, interleukin-6, and nitric oxide synthase 2 mRNA content of both liver and skeletal muscle was increased in TNBS-treated mice; and plasma tumor necrosis factor– α and interleukin-6 concentrations were also elevated. These data suggest that TNBS-induced colitis is independent of a change in muscle protein synthesis but dependent on stimulation of protein degradation via increased expression of muscle-specific atrogenes, which may be mediated in part by the reduction in circulating concentration of IGF-I and the concomitant increase in inflammatory mediators observed in the blood and muscle per se.

T3 acutely increases GH mRNA translation rate and GH secretion in hypothyroid rats

Cytoskeleton controls the stability of transcripts, by mechanisms that involve mRNAs and eEF1A attachment to it. Besides, it plays a key role in protein synthesis and secretion, which seems to be impaired in somatotrophs of hypothyroid rats, whose cytoskeleton is disarranged. This study investigated the: eEF1A and GH mRNA binding to cytoskeleton plus GH mRNA translation rate and GH secretion, in sham-operated and thyroidectomized rats treated with T3 or saline, and killed 30 min thereafter. Thyroidectomy reduced: (a) pituitary F-actin content, and eEF1A plus GH mRNA binding to it; (b) GH mRNA recruitment to polysome; and (c) liver IGF-I mRNA expression, indicating that GH mRNA stability and translation rate, as well as GH secretion were impaired. T3 acutely reversed all these changes, which points toward a nongenomic action of T3 on cytoskeleton rearrangement, which might contribute to the increase on GH mRNA translation rate and GH secretion.

Glucose regulates ghrelin, neuropeptide Y, and the GH/IGF-I axis in the tilapia, Oreochromis mossambicus

In general, a fish's ability to clear glucose is sluggish in relation to mammals, which has lead to the idea that fish are glucose intolerant. It has been reported that circulating glucose levels do fluctuate in response to environmental challenges. Recent reports suggest that glucose may function as a metabolic signal regulating ‘glucosensors’ in the brain in fish, as has been reported in mammals. The current study was designed to investigate the effect of glucose on ghrelin and neuropeptide Y (NPY) signaling in the brain, and on the growth hormone/insulin-like growth factor-I (GH/IGF-I) in the tilapia, Oreochromis mossambicus. Glucose treatment significantly increased plasma and stomach mRNA levels of ghrelin. In the brain, mRNA levels of the ghrelin receptor (GRLN-R) were significantly reduced, whereas NPY mRNA levels were significantly elevated; suggesting that NPY containing neurons may be a “glucosensor” as reported in mammals. Glucose treatment resulted in changes in the GH/IGF-I axis. Liver mRNA levels of both GH receptors (GHR1 and GHR2) were significantly elevated, whereas liver IGF-I mRNA were unaltered by glucose treatment. No change in plasma or pituitary mRNA levels of GH was observed. Glucose significantly reduced plasma IGF-I levels. These data show that glucose regulates endocrine factors involved in appetite, growth, and possibly energy homeostasis, and suggests that glucose may be acting as a signal of metabolic status in fish.

Effects of long term feeding diets differing in protein source and pre-slaughter starvation on biometry, qualitative traits and liver IGF-I expression in large rainbow trout

The effects of feeding two complete extruded diets differing in protein source (fish meal-FM vs. vegetable proteins-VP) over 30 weeks and subsequent 30 days of starvation on biometry, fillet composition and liver IGF-I mRNA were studied in large rainbow trout. At the end of the feeding period, the dietary protein source little affected major biometry traits, dressing out yields and overall adiposity (P<0.05) but fish given the VP diet resulted in higher content of PUFA n-6 fatty acids in muscle (0.46 vs. 0.22 g/100g fillet, P<0.05). Regardless of the previous diet, 30 days of starvation resulted in increased carcass yield (P<0.05), in a slight reduction in adiposity (P<0.05) and of all fatty acids in fillet (P<0.05), except DHA. Liver IGF-I mRNA content was little affected by the test diet and starvation.

High Sucrose Diets Promote Intestinal Epithelial Cell Proliferation and Tumorigenesis in APC Min Mice by Increasing Insulin and IGF-I Levels

Epidemiological studies report that high sucrose consumption is associated with increased risk of colon cancer. One hypothesis is that this association is mediated by elevated circulatory insulin and IGF levels promoting intestinal proliferation. To test this hypothesis, APC Min mice and their wild type littermates were fed, starting at 4 wk of age, sucrose or cornstarch as the sole carbohydrate source in the absence or presence of low levels of dietary sulindac for 10 or 16 wk, respectively. APC Min mice fed sucrose had an increased tumor number in the proximal third of the small intestine in both studies and a higher incidence of papillary colon tumors in the 16-wk feeding study ( P ≤ 0.05). Mice fed sucrose (relative to cornstarch) had higher body weights and greater Ki67-labeling indexes in colonic epithelium than mice fed cornstarch in both feeding studies ( P ≤ 0.05). Furthermore, mice fed sucrose had higher serum glucose and liver IGF-I mRNA concentrations ( P ≤ 0.05) and tended to have higher serum insulin levels ( P = 0.08). These results support the hypothesis that high dietary sucrose intake promotes intestinal proliferation and tumorigenesis by increasing circulating levels of insulin and IGF-I.

Potential Role of Growth Hormone in Impairment of Insulin Signaling in Skeletal Muscle, Adipose Tissue, and Liver of Rats Chronically Treated with Arginine

We have shown that rats chronically treated with Arginine (Arg), although normoglycemic, exhibit hyperinsulinemia and decreased blood glucose disappearance rate after an insulin challenge. Attempting to investigate the processes underlying these alterations, male Wistar rats were treated with Arg (35 mg/d), in drinking water, for 4 wk. Rats were then acutely stimulated with insulin, and the soleus and extensorum digitalis longus muscles, white adipose tissue (WAT), and liver were excised for total and/or phosphorylated insulin receptor (IR), IR substrate 1/2, Akt, Janus kinase 2, signal transducer and activator of transcription (STAT) 1/3/5, and p85alpha/55alpha determination. Muscles and WAT were also used for plasma membrane (PM) and microsome evaluation of glucose transporter (GLUT) 4 content. Pituitary GH mRNA, GH, and liver IGF-I mRNA expression were estimated. It was shown that Arg treatment: 1) did not affect phosphotyrosine-IR, whereas it decreased phosphotyrosine-IR substrate 1/2 and phosphoserine-Akt content in all tissues studied, indicating that insulin signaling is impaired at post-receptor level; 2) decreased PM GLUT4 content in both muscles and WAT; 3) increased the pituitary GH mRNA, GH, and liver IGF-I mRNA expression, the levels of phosphotyrosine-STAT5 in both muscles, phosphotyrosine-Janus kinase 2 in extensorum digitalis longus, phosphotyrosine-STAT3 in liver, and WAT as well as total p85alpha in soleus, indicating that GH signaling is enhanced in these tissues; and 4) increased p55alpha total content in muscles, WAT, and liver. The present findings provide the molecular mechanisms by which insulin resistance and, by extension, reduced GLUT4 content in PM of muscles and WAT take place after chronic administration of Arg, and further suggest a putative role for GH in its genesis, considering its diabetogenic effect.

Upper airway loading induces growth retardation and change in local chondrocyte IGF-I expression is reversed by stimulation of GH release in juvenile rats

Chronic resistive airway loading (CAL) impairs growth in juvenile rats. The effects of CAL on epiphyseal growth plate (EGP) structure and insulin-like growth factor (IGF)-I gene expression have not been explored. Little is known about whether stimulants of endogenous growth hormone (GH) secretion can normalize this growth impairment. This study explored the effect of CAL on circulating and EGP GH/IGF-I pathway GH and the effect of ritanserin (endogenous GH stimulant) on somatic growth and the GH/IGF-I axis. We hypothesized that CAL would lead to a decrease in body temperature (Tb) and alterations of GH/IGF-I pathways, consequently leading to growth retardation. The tracheae of 22-day-old male rats were obstructed by tracheal banding (38 sham-operated control, 42 CAL). Tibial EGP morphometry, liver and EGP IGF mRNA, and serum GH and IGF-I levels were analyzed with quantitative real-time PCR and ELISA. Tb and locomotion activity (MA) were measured with telemetric transmitters inserted into the abdominal cavity. CAL animals had lower Tb and MA despite preserved food consumption. CAL impaired both tibial and tail length gains. Tail and tibial length gains inversely correlated with tracheal resistance. Circulating GH and IGF-I, liver and EGP IGF-I mRNA, and EGP width were decreased in the CAL group. Ritanserin administration to CAL animals normalized circulating and local EGP GH and IGF-I levels and minimized the longitudinal growth impairment. We conclude that CAL causes growth delay associated with alterations in the GH/IGF-I axis. Stimulation of GH release by ritanserin restored both global and local GH/IGF-I pathways, yet growth parameters were only partially restored.

Effects of supplementation frequency on performance, reproductive, and metabolic responses of Brahman-crossbred females1

Two experiments were conducted to compare performance and metabolic responses of beef females consuming low-quality forages and offered an energy supplement based on fibrous byproducts daily (S7) or 3 times per week (S3) at similar weekly rates. In Exp. 1, BW gain, reproductive performance, mRNA expression of hepatic and skeletal muscle genes associated with nutritional metabolism and growth, and concentrations of blood urea nitrogen (BUN), plasma glucose, insulin, and IGF-I were assessed in 56 Brahman x Angus heifers supplemented at a daily rate of 1.0% of BW. Mean BW gain was greater (P = 0.03) for S7 compared with S3 heifers. Treatment x sampling day interactions were detected (P < 0.01) for all blood measurements. Heifers provided S7 had less daily variation in concentrations of BUN, glucose, and insulin, and frequently had greater (P < 0.05) concentrations of IGF-I compared with S3 heifers. Expression of liver IGF-I mRNA was greater (P = 0.04) for S7 heifers compared with S3 heifers. Treatment x day interactions were detected (P </= 0.05) for mRNA expression of liver IGFBP-3, gluconeogenic enzymes, and muscle myostatin because the expression of these transcripts was greater (P < 0.05) for S3 heifers when both treatment groups were supplemented, but was similar or greater (cytosolic phosphoenolpyruvate carboxykinase; P = 0.04) for S7 heifers when only these were supplemented. Attainment of puberty and pregnancy were hastened (P = 0.03 and 0.02, respectively) in S7 heifers compared with S3 heifers. In Exp. 2, 12 Brahman x British mature cows received S3 or S7 for a 3-wk period at a daily rate of 0.5% of BW. Concentrations of BUN were greater for S7 compared with S3 cows (P < 0.03). A treatment x time interaction was detected (P = 0.01) for insulin concentrations because a time effect was significant (P < 0.01) for S3 but not S7 cows. With the advance of the experiment, concentrations of IGF-I increased for S7 (P < 0.01) but not S3 cows (treatment x week interaction; P = 0.02). The combined expression of gluconeogenic enzymes mRNA tended to be greater (P = 0.09) for S3 cows when both treatment groups received supplements, but was greater (P = 0.03) for S7 cows when only these were supplemented (treatment x day interaction; P < 0.01). In conclusion, offering an energy supplement based on fibrous byproducts daily instead of 3 times weekly enhanced the nutritional and metabolic status of forage-fed Brahman-crossbred females, resulting in improved growth and reproductive performance of developing heifers.

Uterine and Hepatic Gene Expression in Relation to Days Postpartum, Estrus, and Pregnancy in Postpartum Dairy Cows

The somatotropic axis consisting of growth hormone, the growth hormone receptor (GHR) insulin-like growth factor (IGF)-I, and IGF binding proteins changes with the stage of lactation and nutrition of the cow and may be 1 mechanism through which lactation and nutrition affect the establishment of pregnancy. The objective of this study was to quantify GHR, IGF-I, and IGF binding protein-2 (IGFBP-2) mRNA in liver and uterine endometrial tissue at 4 stages of lactation (40, 80, 120, and 160 days in milk) and around the time of artificial insemination. Estrus was synchronized with GnRH and PGF2α, and cows were inseminated 12h after estrus. Uterine biopsies were collected immediately before the second injection of PGF2α (before estrus), at the initiation of standing estrus, and 4 d after estrus. Liver biopsies were collected once on 4 d after estrus. The abundance of GHR, IGF-I, and IGFBP-2 mRNA in liver and uterus was determined by real-time quantitative PCR. The amount of liver IGF-I mRNA was positively correlated with plasma IGF-I concentrations. Cows that became pregnant after AI had more GHR and IGFBP-2 mRNA in their liver than cows that did not become pregnant. There was no effect of DIM or pregnancy status on abundance of uterine mRNA; however, uterine GHR and IGF-I mRNA was most abundant at estrus. In summary, cows at different stages of lactation or with different pregnancy statuses had similar quantities of uterine mRNA. In contrast, liver quantities of mRNA differed relative to pregnancy status. These data provide evidence that liver indices of metabolic state may be indicative of pregnancy success.

IGF-I and branchial IGF receptor expression and localization during salinity acclimation in striped bass

The initial response of the IGF-I system and the expression and cellular localization of IGF type-I receptor (IGF-IR) were studied in the gill of a euryhaline teleost during salinity acclimation. Exposure of striped bass (Morone saxatilis) to hyperosmotic and hypoosmotic challenges induced small, transitory (<24 h) deflections in hydromineral balance. Transfer from freshwater (FW) to seawater (SW) induced an initial decrease in plasma IGF-I levels after 24 h in both fed and fasted fish. There was an overall decrease in liver IGF-I mRNA levels after SW transfer, suggesting that decreased plasma levels may be due to a decline in hepatic IGF-I synthesis. No changes were observed in gill IGF-I mRNA, but SW transfer induced an increase in gill IGF-IR mRNA after 24 h. Transfer from SW to FW induced an increase in plasma IGF-I levels in fasted fish. In fed fish, no significant changes were observed in either plasma IGF-I, liver, or gill IGF-I mRNA, or gill IGF-IR mRNA levels. In a separate experiment, FW-acclimated fish were injected with saline or IGF-I prior to a 24-h SW challenge. Rapid regain of osmotic balance following SW transfer was hindered by IGF-I. Immunohistochemistry revealed for the first time in teleosts that IGF-IR and Na(+)-K(+)-ATPase are localized in putative chloride cells at the base of the lamellae, identifying these cells in the gill as a target for IGF-I and IGF-II. Overall the data suggest a hyperosmoregulatory role of IGF-I in this species.

Undernutrition does not alter the activation of β-cell neogenesis and replication in adult rats after partial pancreatectomy

In previous work, we demonstrated that a 65% protein calorie food restriction started during the third trimester of gestation in rats caused a reduced beta-cell mass at 4 days of life that persisted until adult age. In this study with adult undernourished (U) rats, we investigated 1) whether undernutrition affects the beta-cell growth potential and both beta-cell proliferation and differentiation and 2) the implication of the IGFs, highly responsive to nutritional status, in these processes. To this end, we used the 90% pancreatectomy (Px) procedure in U and control (C) adult rats. The results show that, on day 2 after Px, beta-cell replication was significantly higher in C rats, whereas the beta-cell neogenesis was markedly increased in U/Px rats. Both the serum levels of IGF-I and the liver IGF-I mRNA expression were reduced in adult U rats before and after Px compared with C rats. Pancreatic IGF-I mRNA expression was reduced in U animals on day 0. However, on day 2 after Px, the increase of pancreatic IGF-I mRNA expression was significantly higher in U rats than in C rats. These data suggest that beta-cells still have the capacity to regenerate in the adult U rats, with a higher efficiency than C rats on day 2, and that both beta-cell neogenesis and beta-cell replication are stimulated. The increased pancreatic IGF-I mRNA may be instrumental in these processes.