Hepatic Insulin-like Growth factor-I Research Articles

Hepatic mRNA expression and plasma levels of insulin-like growth factor-I (IGF-I) in broiler chickens selected for different growth rates

The hepatic expression and plasma concentrations of IGF-I were investigated in three broiler chicken strains selected for different growth rates (HP-Hubbard-Pettersen, a fast growing strain; NN-Naked-neck, a strain with an intermediate growth rate and a heterozygous genotype, and C-Caipira, a slow growing crossbred strain). The chickens were studied at 1, 21 and 42 days of age and had free access to food throughout the study. Hepatic IGF-I mRNA expression was assessed by dot blot analysis using a randomly labeled chicken IGF-I cDNA as the probe and plasma IGF-I concentrations were assayed by radioimmunoassay. The hepatic levels of IGF-I mRNA increased from 1 to 21 days of age in all strains, with NN chickens showing a higher (p < 0.05) IGF-I expression than the other strains. Plasma IGF-I concentrations increased (p < 0.05) with broiler chicken age, but there were no significant differences among the strains. These results indicate that despite differences in the growth rates among the strains, the changes in the expression of IGF-I mRNA in liver and in the plasma levels of IGF-I were independent of broiler chicken strain, but varied with chicken age.

A quantitative real-time RT-PCR assay for salmon IGF-I mRNA, and its application in the study of GH regulation of IGF-I gene expression in primary culture of salmon hepatocytes

The hormone insulin-like growth factor-I (IGF-I) regulates vertebrate growth. The liver produces most circulating IGF-I, under the control of pituitary growth hormone (GH) and nutritional status. To study the regulation of liver IGF-I production in salmon, we established a primary hepatocyte culture system and developed a TaqMan quantitative real-time RT-PCR assay for salmon IGF-I gene expression. A portion of the coho salmon acidic ribosomal phosphoprotein P0 (ARP) cDNA was sequenced for use as a reference gene. A systematic bias across the 96 well PCR plate was discovered in an initial IGF-I assay, which was corrected when the assay was redesigned. IGF-I mRNA levels measured with the validated assay correlated well with levels measured with an RNase protection assay, and were highest in liver compared with other tissues. We examined the time course of hepatocyte IGF-I gene expression over 48 h in culture, the response to a range of GH concentrations in hepatocytes from fed and fasted fish, and potential effects of variation in IGF-I in the medium. IGF-I gene expression decreased over time in culture in hepatocytes in plain medium, and in cells treated with 5 nM GH with or without a combination of metabolic hormones (1 μM insulin, 100 nM triiodothyronine, and 0.1 nM dexamethasone). GH stimulated IGF-I gene expression at all time points. In cells treated with GH plus metabolic hormones, IGF-I gene expression was intermediate between the controls and GH alone. Increasing concentrations of GH resulted in biphasic IGF-I gene expression response curves in cells from fed and fasted fish, with the threshold for stimulation from 0.5 to 2.5 nM GH, maximal response from 5 to 50 nM, and a reduced response at 500 nM. Medium IGF-I (5 nM) did not affect basal or GH stimulated IGF-I gene expression. This study shows that primary hepatocyte culture and the TaqMan IGF-I assay can be used to study the regulation of hepatic IGF-I gene expression in salmon, and provides the first evidence of a biphasic response to GH concentration in fish hepatocyte culture.

The inhibition of inducible nitric oxide synthase reverts arthritic-induced decrease in pituitary growth hormone mRNA but not in liver insulin-like growth factor I mRNA expression.

Experimental arthritis induced by Freund-adjuvant administration is a model of chronic inflammation and rheumatoid arthritis associated with a decrease in pituitary growth hormone (GH) and hepatic insulin-like growth factor I (IGF-I) gene expression. Excessive nitric oxide (NO) synthesis by inducible NO synthase (iNOS) has been implicated in the pathogenesis of inflammatory illness. Moreover, NO participates in the regulation of GH secretion at both the hypothalamus and the pituitary. We have examined the role of iNOS activation in producing the changes in the GH-IGF-I axis in arthritic rats. Adult male Wistar rats received aminoguanidine or vehicle from day 20, after adjuvant or vehicle injection, until day 28. Two hours and 30 min after the last aminoguanidine injection, all rats were killed by decapitation. Arthritis increased hypothalamic expression of somatostatin mRNA while it decreased pituitary GH mRNA expression, and both effects were prevented by aminoguanidine administration. In arthritic rats, the parallel decrease in serum IGF-I, and in hepatic IGF-I content and mRNA expression, correlates with the decrease in circulating GH concentrations. Aminoguanidine administration to arthritic rats did not modify either serum GH or serum IGF-I concentrations, or hepatic IGF-I mRNA expression. However, aminoguanidine administration to control rats resulted in a decrease in serum GH concentrations and in a decrease in both hepatic IGF-I mRNA expression and serum IGF-I concentrations. These data suggest that NO mediates the arthritis-induced decrease in GH mRNA expression by acting at a hypothalamic level, but it is not involved in the decrease in hepatic IGF-I mRNA expression.

Age-dependent adaptation of the liver thyroid status and recovery of serum levels and hepatic insulin-like growth factor-I expression in neonatal and adult diabetic rats

The effect of treatment with thyroxine (T4) on the hepatic deiodinase (5′D-I) activity and triiodothyronine (T3) content and on insulin-like growth factor-I (IGF-I) secretion and mRNA hepatic expression were studied in neonatal and adult diabetic (D) rats and compared with 4 thyroidectomized (Tx) groups: neonatal and adult Tx rats treated or not with T4. Serum T3 and T4 decreased by 92% in both Tx populations and by 80% to 70% in D adults according to the severity of diabetes: −70 mg/kg body weight (BW) (D70) or 50 mg/kg BW (D50) of streptozotocin (STZ) injected, whereas only a 30% to 33% decrease was found in D neonates. A similar decrease of liver 5′D-I activity and T3 concentrations was found in neonatal and adult Tx rats, whereas a significant reduction in those parameters was observed only in adult diabetics, either D70 or D50, but not in D neonates. Serum levels and liver mRNA expression of IGF-I determined by ribonuclease protection assay, plasma and pituitary growth hormone (GH), plasma insulin, and glycemia were also measured in both D populations. A decrease in circulating IGF-I, previously reported for Tx adult rats, was also found in both D populations. T4 treatment recovered IGF-I and liver T3 in both Tx groups and D neonates, but not in D adults. These results show an age-dependent adaptation of the liver thyroid economy in diabetes, as hepatic 5′D-I does not respond to diabetes in neonates and IGF-I is insensitive to T4 treatment in adult diabetics and suggest a positive correlation between hepatic T3 content and IGF-I expression in conditions of diabetes and Tx.

Growth hormone and insulin-like growth factor I of a Euryhaline fish Cottus kazika: cDNA cloning and expression after seawater acclimation

The four-spine sculpin Cottus kazika is a euryhaline teleost, in which faster growth in seawater (SW) and freshwater (FW) has been reported. In this study, cDNA clones encoding growth hormone (GH) and insulin-like growth factor I (IGF-I) were isolated from this species to examine the involvement of the GH/IGF-I axis in osmotic adaptation. The amino acid sequence of GH predicted from cDNA was highly similar to those of other fish species, 92% to Sparus aurata, 67% to Paralichthys olivaceus, and 63% to Oncorhynchus keta. The predicted sequence of IGF-I was also exhibited high similarity to those of other fishes, 97% to Myxocephalus scorpius, 95% to P. olivaceus, and 81% to O. keta. Tissue distribution of GH and IGF-I mRNA in fish reared in FW and SW was examined by reverse transcription-polymerase chain reaction (RT-PCR). The GH mRNA was detected only in the pituitary gland. The major site of IGF-I mRNA expression was the liver while minor signals were detected in various tissues including the pituitary, gill, fin, heart, spleen, intestine, and kidney. The expression level of GH mRNA in the pituitary was not different between FW- and SW-reared fish. However, the level of IGF-I mRNA in the liver of SW-reared fish was significantly higher than that of FW-reared fish. These results suggest the possible involvement of hepatic IGF-I in SW adaptation of this species.

Effects of fasting on growth hormone/insulin-like growth factor I axis in the tilapia, Oreochromis mossambicus

Effects of fasting on the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis were examined in the tilapia ( Oreochromis mossambicus) acclimated to fresh water. Fasting for 2 weeks resulted in significant reductions in body weight, specific growth rate and hepatosomatic index in both males and females. Significant reductions in specific growth rates were observed after 1 and 2 weeks in both sexes, although the decrease in body weight was not significant in the female. A significant reduction was also seen in the condition factor of females after 2 weeks. No change was seen in the gonadosomatic index in either sex. Two weeks of fasting also produced a significant reduction in plasma IGF-I but not in plasma GH, prolactin (PRL 188) or cortisol. Significant reductions in the hepatic IGF-I mRNA were seen in both sexes. On the other hand, a significant increase was observed in cortisol receptor mRNA in the female liver. Plasma IGF-I levels were correlated significantly with specific growth rate, condition factor and hepatosomatic index, indicating that plasma IGF-I is a good indicator of growth in the tilapia. No change was seen in plasma glucose or osmolality after 2 weeks of fasting. During fasting, tilapia appears to convert metabolic energy from growth to basal metabolism including maintenance of ion and water balance.

Thyroid hormone stimulates hepatic IGF-I mRNA expression in a bony fish, the tilapia Oreochromis mossambicus, in vitro and in vivo

To gain more knowledge about the physiological regulation of hepatic insulin-like growth factor-I (IGF-I) production in bony fish, we examined the potential influence of thyroid hormone (T3, 3,5,3 ′-triiodothyronine) on the expression of IGF-I in the liver of the tilapia Oreochromis mossambicus, using in vitro and in vivo methods. The in vitro experiments were performed using a recently established primary hepatocyte cell culture and IGF-I expression was determined by means of semiquantitative RT-PCR. T3 (100 nM) significantly enhanced the synthesis rate of IGF-I mRNA in short (>8 h) and long (>42 h) time courses. The stimulating effect of T3 was detected already after 1 h. After 4 h, the IGF-I mRNA expression was more than 150% of the starting amount. In long time courses, after 6 h the IGF-I mRNA value was about 170% of that in untreated cells and at the end of the experiment, it was still three times higher than in the control. In addition, the increase in IGF-I mRNA expression evoked by T3 (1 nM to 1 μM) was dose-dependent. In the in vivo approach, 10 individuals of tilapia received 4 daily intraperitoneal injections of T3 (6 μg/g body weight). IGF-I mRNA was assessed using dot blot technique with a tilapia specific IGF-I cRNA probe. The T3 treatment led to an increase of the IGF-I mRNA level up to 45% in the liver compared to the untreated animals. In conclusion, our results show that T3 directly stimulates the hepatic production of IGF-I in the tilapia in vitro and in vivo and indicate that in tilapia liver regulatory mechanisms seem to exist, as they are discussed for mammals.

Growth hormone (GH) hypersecretion and GH receptor resistance in streptozotocin diabetic mice in response to a GH secretagogue.

The growth hormone (GH) and insulin-like growth factor I (IGF-I) axis were studied in streptozotocin (STZ) diabetic and nondiabetic female mice following intravenous (IV) injection of the GH secretagogue (GHS) ipamorelin or saline. On day 14, blood samples were obtained before and 10 minutes after the injection. Livers were removed and frozen for determination of the mRNA expressions of the GH receptor, GH-binding protein, and IGF-I, and hepatic IGF-I peptide. Serum samples were analyzed for GH and IGF-I. Following ipamorelin injection, the GH levels were found to be 150 ± 35 μg/L and 62 ± 11 μg/L in the diabetic compared to the nondiabetic mice (P < .05). Serum IGF-I levels were lower in diabetic than in nondiabetic animals, and rose after stimulation only in the nondiabetic animals. Furthermore, hepatic GH resistance and IGF-I mRNA levels and IGF-I peptide were increased in nondiabetic animals in response to GH stimulation, whereas the low levels per se of all these parameters in diabetic mice were unaffected. The study shows that STZ diabetic mice demonstrate a substantial part of the clinical features of type 1 diabetes in humans, including GH hypersecretion and GH resistance. Accordingly, it is proposed that STZ diabetic mice may be a better model of the perturbations of the GH/IGF-I axis in diabetes than STZ diabetic rats.

Short-Term Infusion of LongR3 Insulin-like Growth Factor (IGF)-I Decreases Hepatic IGF-I mRNA but Not IGF Binding Protein-3 mRNA Expression in Pigs

Infusion of pigs with an insulin-like growth factor-I (IGF-I) analogue (LongR3IGF-I) that does not bind to IGF-binding proteins decreases growth rate and the plasma concentration of growth hormone (GH), IGF-I, IGFBP-3, and insulin. This study was designed to determine whether the decrease is due to changes in IGF-I and IGFBP-3 gene expression. IGF-I or LongR3IGF-I (180 μg/kg/day) was infused into 55-kg finisher pigs for 4 days using Travenol infuser pumps. Plasma IGF-I concentration was measured by radioimmunoassay and plasma IGFBP-3 and IGFBP-2 were estimated by Western ligand blotting. Steady-state levels of IGF-I and IGFBP-3 mRNA were measured by RNase protection assay. Neither IGF-I nor LongR3IGF-I had a significant effect on hepatic IGF-I class 1 mRNA expression, whereas hepatic IGF-I class 2 mRNA expression was significantly reduced by both peptides. Plasma IGFBP-3 levels were unaffected by IGF-I treatment but were reduced by LongR3IGF-I treatment. The decrease in IGFBP-3 was not due to decreased gene expression in porcine liver or kidney, since neither IGF-I nor LongR3IGF-I treatment altered IGFBP-3 mRNA. This study infers a direct effect of the IGF analogue LongR3IGF-I on GH through its inhibition of plasma IGF-I concentration and class 2 IGF-I mRNA. The decrease in plasma IGFBP-3 was not accompanied by a decrease in hepatic or renal IGFBP-3 mRNA, suggesting that in this case, plasma IGFBP-3 protein levels are posttranslationally regulated or are derived from tissues other than liver or kidney.

Differential Regulation of Porcine Hepatic IGF-I mRNA Expression and Plasma IGF-I Concentration by a Low Lysine Diet

The influence of dietary lysine on hepatic insulin-like growth factor-I (IGF-I) gene expression and plasma IGF-I level was investigated. Two male 6-wk-old pigs from each of six litters were used. Each littermate was assigned to one of two diets, control or low lysine (LL), that were isoenergetic and similar in protein content and provided 14.3 MJ digestible energy/kg for both diets, 185 g protein/kg for the control diet and 180 g protein/kg for the LL diet. The control diet contained all essential amino acids in the recommended amounts, including 11.5 g lysine/kg. The LL diet was similar but contained only 7 g lysine/kg. Pigs were pair-fed these diets for 3 wk. Growth rates and feed efficiencies of pigs fed the LL diet were significantly lower than those of pigs fed the control diet (P < 0.01). Plasma IGF-I levels in pigs fed the LL diet were 52% lower than in those fed the control diet (P < 0.01), and the LL group also had lower plasma IGF-binding protein-3 (IGFBP3) levels (P < 0.05). Despite the strikingly lower plasma IGF-I in pigs fed the LL diet, hepatic IGF-I mRNA abundance did not differ between the two treatment groups. We conclude that the reduction in plasma IGF-I caused by reduced dietary lysine may have been due in part to suppression of post-transcriptional events in IGF-I expression. The lower plasma IGFBP3 in pigs fed the LL diet suggests that increased clearance rates of circulating IGF-I may have been involved in this response.

Reduced Insulin-Like Growth Factor-I after Acute Feed Restriction in Lactating Dairy Cows is Independent of Changes in Growth Hormone Receptor 1A mRNA

Growth hormone receptor (GHR) and insulin-like growth factor-I (IGF-I) mRNA decrease in the liver of dairy cows at parturition. Epinephrine is released and feed intake is decreased at the same time. The objective of this study was to determine whether feed restriction and (or) administration of epinephrine could recapitulate the changes in the hepatic GHR 1A and IGF-I mRNA that occur at parturition. Eight lactating cows were randomly assigned to one of two rations (ad libitum or restricted). The cows assigned to the restricted ration were fed 75, 60, 60, and 25% of feed consumed by the ad libitum cows on successive days to mimic the changes in feed intake around parturition. Liver samples were collected by needle biopsy before and after feed restriction. Cows received either 0.02 mg/kg of epinephrine or saline approximately 24h before the second liver biopsy so that a 2 × 2 factorial arrangement of treatments was created. Feed restriction increased plasma nonesterified fatty acids and liver triglyceride percentages and decreased plasma IGF-I concentrations. The decrease in plasma IGF-I after feed restriction was associated with a decrease in IGF-I mRNA in feed-restricted cows. The amount of GHR 1A mRNA did not change after feed restriction. Epinephrine treatment did not affect the amount of GHR 1A or IGF-I mRNA. We conclude that the decrease in feed intake at parturition may be partially responsible for the decrease in IGF-I but may not cause the decrease in GHR 1A.

Insulin-like growth factor-I: compartmentalization within the somatotropic axis?

Insulin-like growth factor-I (IGF-I) is essential for normal growth; igf-1 gene mutations are associated with extreme growth retardation in mice and, very rarely, in humans. The relative contributions of tissue vs. endocrine (hepatic) IGF-I to the regulation of growth has been a fundamental question. New gene targeting technologies are providing answers for these questions.

Chronic salinity adaptation modulates hepatic heat shock protein and insulin-like growth factor I expression in black sea bream.

Black sea bream ( Mylio macrocephalus) hepatic heat shock proteins hsp90, hsp70, and hsp60 were found to be thermally and reversibly inducible as they were elevated 2.0, 3.2, and 2.1 fold, respectively, on acute heat shock and returned to pre-heat-shock levels after a 40-hour recovery period. To establish whether salinity plays a role in regulating heat shock protein (hsp) and insulin-like growth factor-I (IGF-I) expression in a euryhaline marine fish, we adapted groups of juvenile black sea bream to salinities of 50 ppt (hypersaline), 33 ppt (seawater), 12 ppt (isoosmotic), and 6 ppt (hypoosmotic) for 8 months. The lowest levels of hsps were found in fish reared in an isoosmotic salinity and the highest in those adapted to hypersaline and hypoosmotic salinities. Hepatic beta-actin messenger RNA abundance remained unchanged in all groups during salinity adaptation, whereas IGF-I mRNA abundance was highest in isoosmotic adapted black sea bream. This study is the first report of an effect of salinity ranging from hypersaline to hypoosmotic on the expression of different hsp forms and IGF-I in fish, and the possible relationship between environmental salinity, hepatic IGF-I expression, and hsp regulation is discussed.

Dexamethasone decreases serum and liver IGF-I and maintains liver IGF-I mRNA in parenterally fed rats.

Insulin-like growth factor-I (IGF-I) gene expression is regulated by nutritional and hormonal factors. High-dose glucocorticoids decrease food intake, and this confounds studies addressing glucocorticoid effects on IGF-I gene regulation. We investigated alterations in the hepatic IGF-I endocrine system induced by a catabolic dose of dexamethasone (Dex) in rats given adequate nutrition by continuous infusion of total parenteral nutrition (TPN) solution with or without IGF-I administration. The four TPN groups included control, +Dex, +IGF-I, and +IGF-I + Dex (n = 9-11/group). Dex induced a 12% loss of body weight in association with a 50% decrease in hepatic immunoreactive IGF-I, a 10% decrease in serum IGF-I, and no change in steady-state liver IGF-I mRNA or growth hormone (GH) receptor binding. Exogenous IGF-I increased serum IGF-I, attenuated Dex-induced catabolism, and did not reduce hepatic levels of IGF-I and IGF-I mRNA despite decreased serum GH. These data suggest that Dex-induced catabolism is associated with downregulation of the hepatic IGF-I endocrine system at the translational or posttranslational level when adequate nutrition is provided.

Overview of Fish Growth Hormone Family. New Insights in Genomic Organization and Heterogeneity of Growth Hormone Receptors

Growth hormone (GH), prolactin (PRL) and somatolactin (SL) are single chain proteins structurally and functionally related. Fish PRL and GH receptors (PRLR, GHR) have been characterized in several fish species. There is limited evidence of fish PRLR isoforms, but emerging data support the existence of different GHR variants. In gilthead sea bream, black sea bream, turbot and fugu, but not in zebrafish, GHR has retained an exclusive fish intron (10/10A). In gilthead sea bream and turbot, this intron is not alternatively spliced, but the black sea bream intron is either removed or retained during mRNA processing, resulting in a long GHR isoform with a 31 amino acid insertion that does not alter the open reading frame. This or any other GHR variant are not found in gilthead sea bream, but a truncated anchored form has been reported in turbot. The latter GHR isoform comprises extracellular and trans-membrane domains, the first 28 amino acids of the intracellular domain and 21 divergent amino acids before a stop codon. This GHR variant is the result of alternative splicing, being the 3′ UTR and the divergent sequence identical to the sequence of the 5′ end of the 9/10 intron. The physiological significance of different fish GHR isoforms remains unclear, but emerging data provide suitable evidence for season and nutrition related changes in the somatototropic axis activity. The up-regulation of circulating GH together with the decrease of plasma titres of insulin-like growth factor-I (IGF-I), an altered pattern of serum IGF binding proteins and a reduced expression of hepatic IGF-I and GHRs represent a mechanism conserved through vertebrate evolution. It secures the preferential utilization of mobilized substrates to maintain energy homeostasis rather than tissue growth. Somatolactin also changes as a function of season, ration size, dietary amino acid profile and dietary protein source creating opposite plasma GH and SL profiles. There is now direct evidence for a lipolytic effect of fish SL, acting at the same time as an inhibitory factor of voluntary food intake. Indeed, long-term feeding restriction results in the enlargement of the summer GH peak, whereas the SL rise coincident with shortened day length is delayed in juvenile fish until late autumn. These findings agree with the idea that SL may act as a marker of energy surplus, priming some particular process such as puberty onset. However, it remains unclear whether SL works through specific receptors and/or dimers or heterodimers of GH and PRL receptors.

Local and Systemic Expression of Insulin-like Growth Factor-I (IGF-I) mRNAs in Rat after Bone Marrow Ablation

Local and systemic expression of insulin-like growth factor-I (IGF-I) during bone formation was studied using the rat bone marrow ablation model. The temporal expression pattern of IGF-I mRNA in rat femurs was examined. The IGF-I mRNA level was enhanced rapidly after ablation reaching a level threefold greater than basal by day 3 (P < 0.01) and declined to basal or below basal level by day 5. Histological analysis showed that IGF- I immunoreactivity was predominantly associated with the mesenchymal cells at the bone/connective tissue interface and osteoblastic cells at active sites of bone formation. Serum level of IGF-I increased 50 and 130%, respectively (P < 0.005), over the basal level at days 3 and 6. We also investigated the systemic expression of IGF-I in liver and kidney. In contrast, hepatic IGF-I gene expression decreased 37 and 48%, respectively, at days 3 and 6 after marrow ablation (P < 0.001). Kidney IGF-I mRNA levels also fell 13 and 27%, respectively, at days 3 and 6 (P < 0.005). The present findings suggest that locally produced IGF-I during bone formation may not only serve as an autocrine/paracrine factor but also influence systemic expression of IGF-I in other organs.

Induction of choleresis by immunosuppressant FK506 through stimulation of insulin-like growth factor-I production in the liver of rats

FK506 (Tacrolimus) is an effective immunosuppressant currently used worldwide in organ transplantation. Based on our recent findings that insulin-like growth factor-I (IGF-I) is important for the stimulation of choleresis in vivo, in this study we investigated the effect of FK506 on bile flow and the plasma and hepatic levels of IGF-I in rats. Intravenous treatment of rats with FK506 resulted in a significant increase in bile flow, whereas cyclosporin A induced a significant decrease. A significant increase in plasma levels of IGF-I was observed in rats 30 min after a single intravenous administration of FK506. Oral treatment of rats with FK506 for 1 week also resulted in an increase in both plasma and hepatic levels of IGF-I. Overall, this study showed that FK506 treatment increased bile flow and also induced an increase in the plasma and hepatic levels of IGF-I in rats, suggesting that a stimulation of hepatic IGF-I production by FK506 may contribute to its choleretic profile.

METABOLIC AND HORMONAL RESPONSES TO INTERVAL TRAINING AT SEA LEVEL AND MODERATE ALTITUDE

Lactate (LA) measurements are widely used to control training intensity in endurance sports. With regard to an altered LA accumulation pattern at altitude, we questioned whether extensive interval training performed with similar LA values at seal level (SL) and moderate altitude (ALT), yields a comparable metabolic and hormonal stress response. 12 runners (mean ± SEM: 26.6 ± 2.0 yrs, 176.1 ± 2.4 cm, 62.4 ± 2.1 kg, VO2max 64.6 ± 2.0 ml·kg−1), experienced in endurance training, performed an interval training session (IT, 10 ± 1000m, 2 min rest) on the track at SL (350m) with a running velocity corresponding to 112% of the individual anaerobic threshold (IAT). One day later, the athletes moved to ALT (1800 m). After acclimatization (7 days), IT was repeated with a lower velocity (107% IAT) to realize similar LA values compared to SL. LA and heart rate were measured during IT. Blood samples were drawn at rest, 0, 0.3, 3 and 24 h after IT for determination of plasma glucose (Glu), free fatty acids (FA), cortisol (CO), human growth hormone (GH) and insulin-like growth factor-I (IGF-I). LA was similar at SL and ALT (5.4 ± 0.4/5.3 ± 0.3 mmol·l−1) and intraindividual differences (SL/ALT) did not exceed 0.5 mmol·l−1. The rise of Glu after IT was more pronounced at ALT (p < .05), while no differences were found for the increases of FA, CO and GH. A decrease of IGF-I 24 h after IT occurred only at SL (−10.1 ± 3.7, ALT: −1.7 ± 2.9%, p < .05). Conclusions: IT performed with similar LA at SL and ALT, yields comparable increases of FA, CO and GH in athletes, acclimatized to ALT. The behaviour of Glu seems to reflect a higher rate of carbohydrate oxidation during IT at ALT. However, this does not seem to suppress hepatic IGF-I production as shown by unchanged post-exercise IGF-I levels at ALT.

Developmental changes in the mRNA levels of IGF-I and its related genes in the reproductive organs of Japanese quail (Coturnix coturnix japonica).

Summary Insulin-like growth factor-I (IGF-I) is involved in the regulation of growth and differentiation of a variety of vertebrate tissues. The biological actions of IGF-I are mediated mainly by the IGF-I receptor (IGF-IR) and partly by the insulin receptor (IR) and modulated by IGF binding proteins (IGFBP). We conducted studies designed to clarify the possible roles of IGF system in the development of the avian reproductive organs. We cloned cDNAs of IGF-I, IGF-IR, IR and IGFBP-2 of Japanese quail and simultaneously measured the expression of these genes in the quail liver, testis and oviduct at different ages using a lysate RNase protection assay. Hepatic IGF-I mRNA levels increased rapidly and remained elevated during the rapid-growing period, which coincided with the period of rapid increase in testicular weight. IGF-I mRNA was detected at each stage of developing testis examined. Its level was high at the early stage and decreased with age. IGFBP-2 mRNA in testis exhibited a similar expression pattern to that of IGF-I, whereas a divergence in IGF-I and IGF-IR gene expression was observed. Both IGF-IR and IR mRNAs increased when the testis grew rapidly and decreased when sexual maturation was almost completed. These results suggest that IGF-I may serve as an autocrine/paracrine regulator as well as an endocrine regulator in the testicular development and function of Japanese quail. In the oviduct, IGF-I, IGF-IR, IR and IGFBP-2 mRNAs were also developmentally regulated. A rapid growth of the oviduct was accompanied by a significant increase in the level of IGF-I mRNA. The expression of genes encoding IGF-IR, IR and IGFBP-2 in the oviduct exhibited a similar developmental change to that of IGF-I. These results suggest that IGF-I mainly works in an autocrine and/or paracrine manner in the oviduct during the development of this organ. The findings of the present study provide further evidence of an important role for IGF system in the development and function of the avian reproductive system.

Cooperation of liver cells in health and disease.

Cooperation of liver cells in health and disease.