Liver Igf1 mRNA Research Articles

Gene expression profiling and physiological adaptations of pearl spot (Etroplus suratensis) under varying salinity conditions

Eutroplus suratensis (Pearl spot) is naturally found in estuarine environments and has been noted to have a high salinity tolerance. By examining the impact of various salinity levels on the growth and survival of pearl spot, the present study aims to enhance aquaculture profitability by assessing their adaptability and physiological adjustments to changes in salinity and determining their potential to acclimate to a broad range of salinity regimes. Results revealed no mortality in the control group (0 ppt), and in 15, 25 and 35 ppt treatment groups. However, the remaining groups (45, 60, and 75 ppt) showed differing levels of mortality with 44 % mortality observed in the 45 ppt group and 100 % mortality in both the 60 and 75 ppt groups. The expression analysis showed that liver IGF-1 mRNA expression increased by 2.6-fold at 15 ppt, and HSP70 mRNA expression in the liver also showed a significant increase with rising salinity levels. In addition, OSTF1 expression exhibited an increase at 15 ppt, whereas SOD and CAT expression reached their highest levels at 25 ppt. At 15 ppt, the expression of NKA mRNA increased significantly by 2.8-fold. The study's overall findings suggested that utilizing a salinity level of 15 ppt for pearl spot production could be viable for profitable aquaculture.

Astragalus Extract Mixture HT042 Increases Longitudinal Bone Growth Rate by Upregulating Circulatory IGF-1 in Rats.

Astragalus extract mixture HT042 is a standardized ingredient of health functional food approved by Korean FDA with a claim of “height growth of children.” HT042 stimulates bone growth rate and increases local IGF-1 expression in growth plate of rats which can be considered as direct stimulation of GH and its paracrine/autocrine actions. However, it remains unclear whether HT042 stimulates circulatory IGF-1 which also plays a major role to stimulate bone growth. To determine the effects on circulatory IGF-1, IGF-1 and IGFBP-3 expressions and phosphorylation of JAK2/STAT5 were evaluated in the liver after 10 days of HT042 administration. HT042 upregulated liver IGF-1 and IGFBP-3 mRNA expression, IGF-1 protein expression, and phosphorylation of JAK2/STAT5. HT042 also increased bone growth rate and proliferative zonal height in growth plate. In conclusion, HT042 stimulates bone growth rate via increment of proliferative rate by upregulation of liver IGF-1 and IGFBP-3 mRNA followed by IGF-1 protein expression through phosphorylation of JAK2/STAT5, which can be regarded as normal functioning of GH-dependent endocrine pathway.

Effects of nutrient intake level on mammary parenchyma growth and gene expression in crossbred (Holstein × Gyr) prepubertal heifers.

This study investigated the effects of increased nutrient intake levels on prepubertal mammary parenchyma development in crossbreed (Holstein × Gyr) dairy heifers. Eighteen heifers age 3 to 4 mo were fed 1 of 3 nutrient intake levels (n=6 per treatment) designed to sustain an average daily gain of 0.0kg/d (maintenance, MA), 0.5kg/d (low gain, LG), or 1.0kg/d (high gain, HG). Serum blood samples collected on d 42 and 84 after a 12-h fast were analyzed for triglycerides, leptin, insulin, and insulin-like growth factor 1 (IGF-1). Liver and mammary parenchyma were biopsied on d 42 and harvested on d 84 for gene expression analysis. Parenchyma samples were also used for biochemical and histological analysis. Mammary parenchyma weight was lower in HG than in MA or LG heifers, but mammary extraparenchymal fat was greater in HG heifers than in other groups. Heifers fed the HG diet had a greater fraction of ether extract in their parenchyma than the others and a smaller fraction of crude protein in their parenchyma than MA heifers. Moreover, the HG and LG heifers had greater body fat mass than MA heifers. Nutrient intake level had no effect on the number of intraparenchymal adipocytes. Heifers fed the HG diet had greater serum IGF-1 than the others, and serum insulin was lower in the MA than the HG or LG heifers. Liver GHR, IGF1, and IGFBP3 mRNA expression was higher, but IGFBP2 mRNA was lower in HG heifers than in others. The parenchyma mRNA expression of lipogenic markers, such as CD36, ACCA, FASN, and ADIPOR1, was upregulated by nutrient intake level. Significant nutrient intake × time interactions for lipogenic genes during the experimental period indicated variable gene expression depending on the time point of prepubertal mammary gland development. Overall, our data suggest that enhancing nutrient intake increased body fat accumulation and lipogenesis in the mammary gland to the detriment of parenchyma growth. Moreover, increased lipogenesis in the parenchyma of HG heifers may indicate that fat accumulation occurred because of adipocyte hypertrophy and not differences in adipogenesis. The implications of these results for milk yield needs to be elucidated.

Growth hormone receptors in the atherinid Odontesthes bonariensis: characterization and expression profile after fasting-refeeding and growth hormone administration.

In order to improve the understanding of pejerrey Odontesthes bonariensis, growth hormone (Gh)-insulin-like growth factor-1(Igf1) axis, O. bonariensis growth hormone receptor type 1 (ghr1) and type 2 (ghr2) mRNA sequences were obtained. Both transcripts were ubiquitously expressed except in kidney, encephalon and anterior intestine. Alternative transcripts of both receptors were found in muscle. Interestingly, two different ghr2 transcripts with alternative polyadenylation (APA) sites located in the long 3' untranslated region (UTR-APA) were also found in liver. Hepatic ghr1, ghr2 and insulin-like growth factor type 1 (igf1) transcript levels were examined under two different metabolic conditions. In the first experimental condition, fish were fasted for 2 weeks and then re-fed for another 2 weeks. Despite igf1 mRNA relative expression did not show significant differences under the experimental period of time examined, both ghr transcripts decreased their expression levels after the fasting period and returned to their control levels after re-feeding. In the second treatment, recombinant O. bonariensis growth hormone (r-pjGh) was orally administered once a week. After 4 weeks of treatment, liver igf1, ghr1 and ghr2 mRNA relative expression increased (13, 4·5 and 2·1 fold, P < 0·05) compared to control values. These results add novel information to the growth hormone-insulin-like growth factor system in teleosts.

Sodium perchlorate disrupts development and affects metamorphosis- and growth-related gene expression in tadpoles of the wood frog (Lithobates sylvaticus)

Numerous endocrine disrupting chemicals can affect the growth and development of amphibians. We investigated the effects of a targeted disruption of the endocrine axes modulating development and somatic growth. Wood frog (Lithobates sylvaticus) tadpoles were exposed for 2weeks (from developmental Gosner stage (Gs) 25 to Gs30) to sodium perchlorate (SP, thyroid inhibitor, 14mg/L), estradiol (E2, known to alter growth and development, 200nM) and a reduced feeding regime (RF, to affect growth and development in a chemically-independent manner). All treatments experienced developmental delay, and animals exposed to SP or subjected to RF respectively reached metamorphic climax (Gs42) approximately 11(±3) and 17(±3) days later than controls. At Gs42, only SP-treated animals showed increased weight and snout-vent length (P<0.05) relative to controls. Tadpoles treated with SP had 10-times higher levels of liver igf1 mRNA after 4days of exposure (Gs28) compared to controls. Tadpoles in the RF treatment expressed 6-times lower levels of liver igf1 mRNA and 2-times higher liver igf1r mRNA (P<0.05) at Gs30. Tadpoles treated with E2 exhibited similar developmental and growth patterns as controls, but had increased liver igf1 mRNA levels at Gs28, and tail igf1r at Gs42. Effects on tail trβ mRNA levels were detected in SP-treated tadpoles at Gs42, 40days post-exposure, suggesting that the chemical inhibition of thyroid hormone production early in development can have long-lasting effects. The growth effects observed in the SP-exposed animals suggest a relationship between TH-dependent development and somatic growth in L. sylvaticus tadpoles.

β-Carotene Increases Muscle Mass and Hypertrophy in the Soleus Muscle in Mice.

Supplements and naturally occurring nutraceuticals effective for maintenance or enhancement of skeletal muscle mass are expected to contribute to prevention of decreased mobility and increased risk of developing metabolic diseases. However, information about available food components remains widely unavailable. In the present study, we investigated the effects of dietary β-carotene on the quantity and quality of skeletal muscle under physiological conditions. Male ddY mice (8 wk old) were orally administered β-carotene (0.5 mg once daily) for 14 d. Dietary β-carotene had no influence on body weight, but increased the soleus muscle/body weight ratio. The cross-sectional area (CSA) in muscle fibers of the soleus muscle was increased, indicating that administration of β-carotene induces muscle hypertrophy. In the soleus muscle of the β-carotene-administered mice, twitch force tended to be increased (p=0.06) and tetanic force was significantly increased, whereas specific force (force per CSA) remained unchanged. Dietary β-carotene increased the mRNA level of insulin-like growth factor 1 (Igf-1) as its splicing variant Igf-1ea, but had no influence on the liver Igf-1 mRNA level or serum IGF-1 level. β-Carotene promoted protein synthesis in the soleus muscle and reduced levels of ubiquitin conjugates, but had no influence on the mRNA levels of two atrogenes, Atrogin-1 and Murf1. On the other hand, β-carotene had no influence on the processing of the autophagy marker protein light chain 3. These results indicate that in mice, administration of β-carotene increases mass and induces functional hypertrophy in the soleus muscle, perhaps by promoting IGF-1-mediated protein synthesis and by reducing ubiquitin-mediated protein degradation.

Effects of calf weaning age and subsequent management system on growth and reproductive performance of beef heifers.

Brahman × British crossbred heifers (n = 40 and 38 heifers in yr 1 and 2, respectively) were used to evaluate the effects of calf weaning age and subsequent management system on growth and reproductive performance. On d 0, heifers were ranked by BW (89 ± 16 kg) and age (72 ± 13 d) and randomly assigned to a conventional management group that was normally weaned on d 180 (NW; n = 10 heifers annually) or early weaned (EW) on d 0 and 1) limit fed a high-concentrate diet at 3.5% of BW (as fed) in drylot until d 180 (EW180; n = 10 heifers annually), 2) limit fed a high-concentrate diet at 3.5% of BW (as fed) in drylot until d 90, then grazed on Bahiagrass pastures until d 180 (EW90; n = 10 heifers annually), or 3) grazed on annual ryegrass pastures until d 60 (yr 1; n = 10 heifers) or 90 (yr 2; n = 8 heifers), then on Bahiagrass pastures until d 180 (EWRG). On d 180, all heifers were grouped by treatment and rotated on Bahiagrass pastures until d 390. Grazing heifers were supplemented at 1.0% BW until d 180 and at 1.5% BW from d 180 to 390. From d 0 to 90, EW180 and EW90 heifers were heavier (P ≤ 0.02) than NW and EWRG heifers, whereas NW heifers tended (P = 0.09) to be heavier on d 90 than EWRG heifers. In yr 1 and 2, EW180 heifers were heaviest (P < 0.0001) on d 180. In yr 1, EWRG heifers were lightest (P < 0.0001), whereas EW90 and NW heifers had similar BW (P = 0.58). Conversely, EW90, EWRG, and NW heifers achieved similar BW on d 180 of yr 2 (P ≥ 0.18). Positive correlations were detected (P ≤ 0.05) between liver IGF-1 mRNA abundance on d 90 and ADG from d 0 to 90 and between liver IGF-1 mRNA abundance on d 180 and ADG from d 90 to 180. The EW180 heifers were youngest (P ≤ 0.01) at puberty. From d 260 to 340, the percentage of pubertal heifers was greater (P ≤ 0.03) for EW90 vs. NW heifers but did not differ (P ≥ 0.15) between EWRG and NW heifers. The ADG from d 0 to 90 and the plasma IGF-1 on d 90 and 180 explained approximately 34% of the variability in age at puberty. In summary, the EW90 and EW180 heifer management systems evaluated in this study altered the BW at the time of NW and were good alternatives for anticipating puberty achievement compared to NW heifers.

Responses of insulin-like growth factor (IGF)-I and two IGF-binding protein-1 subtypes to fasting and re-feeding, and their relationships with individual growth rates in yearling masu salmon (Oncorhynchus masou)

Two subtypes of insulin-like growth factor binding protein (IGFBP)-1 are present in salmon blood and they are both up-regulated under catabolic conditions such as stress. The present study examined effects of fasting and re-feeding on IGFBP-1a (28-kDa form) and IGFBP-1b (22-kDa form) both at mRNA and protein levels along with IGF-I and RNA/DNA ratio in yearling masu salmon. Fish were individually tagged and assigned to one of three treatments: Fed, Fasted or Re-fed. Circulating IGF-I levels significantly decreased after fasting for 5weeks and were positively correlated with individual growth rates. Liver igf-1 mRNA levels were not affected by the treatment. Muscle RNA/DNA ratio did not respond to fasting nor showed correlations with growth rates. Circulating IGFBP-1a and IGFBP-1b increased during fasting and decreased after re-feeding. Both serum levels were inversely correlated with growth rates, while IGFBP-1b had consistent negative relationships with growth rates. Fasting/re-feeding also affected their mRNA levels in the liver. These results suggest that circulating IGF-I and IGFBP-1b could serve as positive and negative indices of growth, respectively, in masu salmon. Different sensitivities of IGBP-1a and IGFBP-1b may be useful to assess a broad range of catabolic conditions when they are combined.

Relationships between gill Na+,K+-ATPase activity and endocrine and local insulin-like growth factor-I levels during smoltification of masu salmon (Oncorhynchus masou)

We established profiles of insulin-like growth factor (IGF)-I mRNA in the liver, gill and white muscle and circulating IGF-I during smoltification of hatchery-reared masu salmon, and compared with that of gill Na+,K+-ATPase (NKA) activity. Gill NKA activity peaked in May and dropped in June. Liver igf1 mRNA was high in March and decreased to low levels thereafter. Gill igf1 increased from March, maintained its high levels during April and May and decreased in June. Muscle igf1 mRNA levels were relatively high during January and April when water temperature was low. Serum IGF-I continuously increased from March through June. Serum IGF-I during March and May showed a positive correlation with NKA activity, although both were also related to fish size. These parameters were standardized with fork length and re-analyzed. As a result, serum IGF-I and gill igf1 were correlated with NKA activity. On the other hand, samples from desmoltification period (June) that had high serum IGF-I levels and low NKA activity disrupted the relationship. Expression of two IGF-I receptor (igf1r) subtypes in the gill decreased in June, which could account for the disruption by preventing circulating IGF-I from acting on the gill and retaining it in the blood. The present study suggests that the increase in gill NKA activity in the course of smoltification of masu salmon was supported by both endocrine and local IGF-I, and the decrease during desmoltification in freshwater was due at least in part to the down-regulation of gill IGF-I receptors.

乾乳牛における短期絶食が血中エストラジオール-17β、IGF-1濃度および肝臓IGF-1 mRNA発現に及ぼす影響

乾乳牛における短期絶食が血中エストラジオール-17β、IGF-1濃度および肝臓IGF-1 mRNA発現に及ぼす影響

Effect of feeding level on serum IGF1 response to GH injection

This study was conducted to further understand the mechanism by which nutrition modulates GH-induced changes in serum IGF1 concentration in cattle. Cows were fed hay only or corn-based concentrates in addition to hay for 8 weeks. At week 8, serum concentrations of IGF1, IGF-binding protein 3 (IGFBP3), and acid-labile subunit (ALS) as well as their mRNA levels in liver were determined immediately before and 7 days after an injection of GH formulated for sustained release. GH injection caused greater increases in both serum IGF1 concentration and liver IGF1 mRNA expression in the cows fed concentrates than in those fed hay. In the cows fed concentrates, the magnitude of the GH-induced increase in serum IGF1 concentration was, however, much greater than that in liver IGF1 mRNA expression. This difference was not due to GH-induced IGF1 mRNA being translated more efficiently. GH injection also induced greater increases in serum IGFBP3 and ALS concentrations in the cows fed concentrates than fed hay. The injection, however, did not induce a greater increase in IGFBP3 or ALS mRNA in the cows fed concentrates than fed hay. These data and the fact that the ternary complex of IGF1/IGFBP3/ALS stabilizes each of the components in the blood suggest that in cows, increased nutrition enhances serum IGF1 response to GH not only by increasing IGF1 mRNA response to GH in the liver, but also by elevating IGFBP3 and ALS concentrations in the blood.

The influence of gestational zinc deficiency on the fetal insulin-like growth factor axis in the rat

The insulin-like growth factor (IGF) axis, a key regulator of embryonic growth and development, is exquisitely sensitive to the nutrient status of the animal. In addition to macronutrient deficiencies, zinc deficiency can impact the IGF axis. Gestational zinc deficiency is teratogenic, resulting in intrauterine growth retardation and structural abnormalities. The aim of this study was to investigate the effects of gestational zinc deficiency on the fetal IGF axis in a rat model. From gestation day (GD) 0.5, dams consumed zinc-deficient (ZD, 0.3 mg zinc/kg) or control (25 mg zinc/kg) diet ad libitum, while a third group of dams consumed the control diet in amounts equivalent to the food intake of the ZD dams (Paired group). On GD 19.5 fetal tissue, blood and amniotic fluid were collected. Fetal growth was significantly reduced by zinc deficiency compared with the Paired and Control groups. Fetuses from the Paired group were smaller compared with the Control, but only ZD fetuses had structural malformations. Amniotic fluid IGF-1 concentrations were significantly lower in the Paired group than in the ZD and Control groups. Plasma of ZD fetuses contained lower levels of IGF binding protein-1 when compared with fetuses in the Paired and Control groups. Fetal liver IGF-1 mRNA levels were lower in the ZD fetuses than in the Paired and Control fetuses. These observations suggest that differences in the fetal IGF axis between ZD and Paired groups contribute to the poor pregnancy outcome and enhanced fetal growth retardation observed with zinc deficiency.

Short communication: Growth hormone receptor expression in two dairy breeds during the periparturient period

The growth hormone receptor (GHR) 1A mRNA decreases after calving in the liver of Holstein dairy cows and may coordinate nutrient partitioning. The hypothesis that the decrease in GHR1A mRNA around the time of calving was characteristic of a second dairy breed was tested by examining Guernsey cows in addition to Holstein cows. Holstein and Guernsey cows were housed together and paired by parity and expected calving date. Liver biopsies and blood samples were collected prepartum (d −20±1) and postpartum on d 3, and d 14±1. The amounts of GHR1A, GHR1B, GHR1C, and insulin-like growth factor (IGF)1 mRNA were determined by quantitative reverse transcription polymerase chain reaction. Blood concentrations of growth hormone (GH) and IGF1 were measured by RIA. Both breeds underwent a decrease in GHR1A mRNA, a decrease in liver IGF1 mRNA, a decrease in blood IGF1, and an increase in blood GH after calving. The decrease in liver GHR1A and IGF1 mRNA after calving may be an inherent characteristic of dairy breeds that enables nutrient partitioning for greater milk production. Independent genetic selection in 2 dairy breeds seemingly exploited a similar mechanism, reduced GHR1A expression, to decrease blood IGF1 and increase blood GH, a key hormone involved in nutrient partitioning.

SnoRNA Snord116 (Pwcr1/MBII-85) Deletion Causes Growth Deficiency and Hyperphagia in Mice

Prader-Willi syndrome (PWS) is the leading genetic cause of obesity. After initial severe hypotonia, PWS children become hyperphagic and morbidly obese, if intake is not restricted. Short stature with abnormal growth hormone secretion, hypogonadism, cognitive impairment, anxiety and behavior problems are other features. PWS is caused by lack of expression of imprinted genes in a ∼4 mb region of chromosome band 15q11.2. Our previous translocation studies predicted a major role for the C/D box small nucleolar RNA cluster SNORD116 (PWCR1/HBII-85) in PWS. To test this hypothesis, we created a ∼150 kb deletion of the >40 copies of Snord116 (Pwcr1/MBII-85) in C57BL/6 mice. Snord116del mice with paternally derived deletion lack expression of this snoRNA. They have early-onset postnatal growth deficiency, but normal fertility and lifespan. While pituitary structure and somatotrophs are normal, liver Igf1 mRNA is decreased. In cognitive and behavior tests, Snord116del mice are deficient in motor learning and have increased anxiety. Around three months of age, they develop hyperphagia, but stay lean on regular and high-fat diet. On reduced caloric intake, Snord116del mice maintain their weight better than wild-type littermates, excluding increased energy requirement as a cause of hyperphagia. Normal compensatory feeding after fasting, and ability to maintain body temperature in the cold indicate normal energy homeostasis regulation. Metabolic chamber studies reveal that Snord116del mice maintain energy homeostasis by altered fuel usage. Prolonged mealtime and increased circulating ghrelin indicate a defect in meal termination mechanism. Snord116del mice, the first snoRNA deletion animal model, reveal a novel role for a non-coding RNA in growth and feeding regulation.

Zinc deficiency induced disruption in the fetal and maternal rat insulin‐like growth factor axis

The insulin-like growth factor (IGF) axis is a key regulator of embryonic growth and development. This system is exquisitely sensitive to nutrient deficiencies including Zn deficiency (ZnD). We investigated the effects of ZnD on the maternal and fetal IGF axis at gestation day (GD) 19. Pregnant rats consumed ZnD (0.5 ppm Zn) or Control (25 ppm Zn) diet, or were restricted (Paired) to ZnD intake levels of control diet. Maternal liver and serum, and fetal liver, plasma and amniotic fluid were collected. Maternal serum IGF-1 concentrations (measured by radioimmunoassay) were inversely related to hepatic mRNA levels (determined by real-time RT-PCR). This outcome was strongest in the Paired and ZnD compared to Controls, suggesting a feed back mechanism in response to ZnD and food restriction. Fetal liver IGF-1 mRNA was significantly elevated in the ZnD fetuses, an effect not related to reduced maternal food intake but well correlated with the severe disruption in development observed only in the ZnD group. Maternal serum, fetal plasma and amniotic fluid were labeled with 125I-IGF-1, and native FPLC was used to asses IGFBP-1, -2, -3 binding. IGFBP1/2 was significantly elevated in the Paired but not ZnD dams. Similar patterns were observed in fetal plasma with no detectable differences in amniotic fluid. In summary, the differences in fetal IGF axis between ZnD and Paired groups may contribute to the formers teratogenic outcome.

Effects of recombinant mouse growth hormone treatment on growth and body composition in GHRH knock out mice

Objective GH deficiency (GHD) causes growth failure and alterations in body composition both in humans and mice. Mouse models of GHD are used to study the effect of GH replacement therapy on these parameters. As the administration of human GH to mice causes development of antibodies and progressive reduction of its effectiveness, the use of species-specific GH is recommended. To determine the optimal GH replacement schedule in GHD mice, and to study its effect on body composition, we treated mice with targeted ablation of the GHRH gene (GHRH knock out-GHRHKO) with recombinant mouse GH (rmGH). Design One week-old GHRHKO male animals received either placebo or one of two different regimens of escalating doses of rmGH: R1: 30 μg/daily (1st week), 50 μg/daily (2nd week), 70 μg/daily (3rd–4th week); R2: 15 μg/twice a day (1st week), 25 μg/twice a day (2nd week), 35 μg/twice a day (3rd–4th week). Sex- and age-matched wild-type (WT) animals served as controls. At the end of the study we measured body length and weight, tibia and femur length, and body composition. Results While R1 normalized all growth parameters (TBW, N–A, femur, tibia length), R2 mice achieved significantly higher TBW, N–A and femur length when compared to WT. Body composition abnormalities (increased subcutaneous fat and reduced lean mass) were completely reverted by both treatment schedules. None of the GH-induced parameter modification described above was reflected in parallel changes in circulating serum IGF-1 and liver IGF-1 mRNA. Conclusions Our findings indicate that in GHD mice body composition changes are reverted by rmGH and that twice/daily is more effective than daily administration.

Effects of environmental temperature on IGF1, IGF2, and IGF type I receptor expression in rainbow trout ( Oncorhynchus mykiss)

Recently, we have demonstrated in rainbow trout that environmental temperature may, independently of nutritional status, directly stimulate plasma growth hormone (GH) that is recognised as being an insulin-like growth factor (IGF) system regulator. The aim of this study was to determine whether temperature may directly regulate the IGF system or indirectly regulate it through plasma GH or nutritional status. For this purpose, rainbow trout were reared at 8, 12, or 16 °C and fed either ad libitum (similar nutritional status) to evidence the global effect of temperature, or with the same ration (1.2% body weight/day), to determine the temperature effect in fish with the same growth rate. Endocrine and autocrine/paracrine regulations of the IGF system were determined by measuring plasma IGF1 and IGF2, liver and muscle IGF1 and IGF2 mRNA as well as IGFRIa, IGFRIb mRNA, and the quantity of IGF type I receptor in muscle. Our results show that neither rearing temperature nor the nutritional status of fish affected the expression of both IGF receptor genes in muscle. Nevertheless, the quantity of IGF type I receptor determined by a binding study, appeared to be inversely proportional ( P<0.05) to the rearing temperature without any relationship with nutritional status, suggesting a direct effect of temperature on its turnover. After 2 weeks of treatment, the levels of IGF1 mRNA in muscle at 8 °C were 2-fold higher ( P<0.05) than at 16 °C in both ad libitum and restricted feed fish, whereas after 6 weeks, this difference was no longer observed. In both experiments, the levels of plasma IGF2 were 10-fold higher than the levels of plasma IGF1 (mean 105 ± 3.0 versus 13.5 ± 0.6 ng/ml), and plasma levels were correlated with their respective mRNA liver concentrations ( r 2=0.14 and 0.25, respectively; P<0.01). In the ad libitum feeding experiment, plasma and mRNA levels of IGF1 were related to the rearing temperature ( P<0.05), while for IGF2 no effect was seen. In contrast, in the restricted feeding experiment, plasma and IGF2 mRNA levels were inversely proportional to the rearing temperature ( P<0.0001) while plasma IGF1 was unaltered. Levels of plasma IGF1 were related to the growth rate in both experiments, while levels of plasma IGF2 appeared to be associated with the nutritional status of the fish. Our results suggest that the autocrine/paracrine expression of IGF1 and IGF2 in muscle is not a key regulator of the growth promoting effect of temperature. Conversely, temperature seems to promote growth through IGF1 secretion by the liver following GH stimulation, and impairment of nutritional status would prevent the IGF1 stimulation by temperature. In addition, the growth-promoting effect of temperature did not affect plasma IGF2, which appeared to be more related to the metabolic status of the fish.

Ontogenic study of insulin-like growth factor-1 and growth hormone receptor mRNA expression in porcine liver and skeletal muscle

AbstractThe growth hormone-insulin-like growth factor (GH-IGF) axis is involved in the control of postnatal growth in all animals studied to date. At birth, blood levels of IGF-1 are low, although levels of GH are high. Thus a switching occurs during the postnatal period, which involves an increase in liver GH-receptors (GHR). This study investigates the changes in serum IGF-1 and IGF-1 and GHR mRNA in liver and skeletal muscle of growing pigs. The period from birth to 20 days of age showed a gradual increase in both IGF-1 and GHR mRNA expression by the liver, thus accounting for the gradual increase in serum IGF-1. The IGF-1 mRNA expressed was found to be predominantly class 1 transcripts with very few class 2 transcripts. There was a plateau of liver IGF-1 mRNA levels after 20 days and up to 140 days, even though the expression of GHR mRNA continued to increase. The levels of expression of the two genes were found to correlate in the first 20-day period (r = 0·76,P&lt; 0·005), but not in the later period (r = 0·44,P&gt; 0·05).Levels of expression of both genes in the LD muscle were highly variable, with no age related changes being observed. However, a significant negative correlation of expression of the two genes was observed (R = 0·60,P&lt; 0·001), with the correlation still being significant in the two age periods.The data are consistent with a likely initial dependence for postnatal growth upon GH-stimulated IGF-1 mRNA expression by the liver, up to 20 days of age. After this time, hepatic expression of IGF-1 mRNA reaches a plateau, even though the serum IGF-1 and hepatic GHR mRNA levels continue to rise. A possible explanation for this could be an increase in either turn-over or stability of IGF-1 mRNA, giving rise to increased levels of peptide with no apparent change in mRNA level. Another possibility is that an increased expression/production of the IGF-binding proteins leads to an increase in the half-life of the peptide in the circulation.