A novel, noninvasive transdermal fluid sampling methodology: IGF-I measurement following exercise

This study tested the hypothesis that transdermal fluid (TDF) provides a more sensitive and accurate measure of exercise-induced increases in insulin-like growth factor-I (IGF-I) than serum, and that these increases are detectable proximal, but not distal, to the exercising muscle. A novel, noninvasive methodology was used to collect TDF, followed by sampling of total IGF-I (tIGF-I) and free IGF-I (fIGF-I) in TDF and serum following an acute bout of exercise. Experiment 1: eight men (23 ± 3 yrs, 79 ± 7 kg) underwent two conditions (resting and 60 min of cycling exercise at 60% Vo(2)(peak)) in which serum and forearm TDF were collected for comparison. There were no significant changes in tIGF-I or fIGF-I in TDF obtained from the forearm or from serum following exercise (P > 0.05); however, the proportion of fIGF-I to tIGF-I in TDF was approximately fourfold greater than that of serum (P ≤ 0.05). These data suggest that changes in TDF IGF-I are not evident when TDF is sampled distal from the working tissue. To determine whether exercise-induced increases in local IGF-I could be detected when TDF was sampled directly over the active muscle group, we performed a second experiment. Experiment 2: fourteen subjects (22 ± 4 yr, 68 ± 11 kg) underwent an acute plyometric exercise condition consisting of 10 sets of 10 plyometric jumps with 2-min rest between sets. We observed a significant increase in TDF tIGF-I following exercise (P ≤ 0.05) but no change in serum tIGF-I (P > 0.05). Overall, these data suggest that TDF may provide a noninvasive means of monitoring acute exercise-induced changes in local IGF-I when sampled in proximity to exercising muscles. Moreover, our finding that the proportion of free to tIGF-I was greater in TDF than in serum suggests that changes in local IGF-I may be captured more readily using this system.     

Interactive effect of exercise training and growth hormone administration on glucose tolerance and muscle GLUT4 protein expression in rats

The insulin-resistance effect of growth hormone (GH) administration has been frequently reported. The present study investigated the effect of GH administration on glucose tolerance and muscle GLUT4 protein expression in exercise-trained and untrained rats. Forty-eight rats were weight-matched and assigned to the following 4 groups: control, GH, exercise training, and exercise training + GH groups. After 2 weeks of GH injections (65 µg/kg/day) and exercise training, the glucose tolerance and insulin response were measured in these rats. The GLUT4 protein level, glycogen storage, and citrate synthase activity were determined in red gastrocnemius and plantaris muscles. Daily GH administration elevated the curves of the oral glucose tolerance test and insulin response compared with those of saline-injected control rats. Furthermore, exercise training completely eliminated this GH-induced insulin resistance as determined 18 h after the last bout of exercise training. Additionally, exercise training significantly increased muscle glycogen storage and GLUT4 protein levels. GH administration did not affect the GLUT4 protein and glycogen storage increases induced by exercise training, but the citrate synthase activity in the plantaris muscle was further elevated by GH administration to a level above that induced by training. In conclusion, this is the first study that demonstrates that regular exercise training prevents GH-induced insulin-resistance side effect in rats.     

Time course of molecular responses of human skeletal muscle to acute bouts of resistance exercise.

Resistance exercise (RE) training, designed to induce hypertrophy, strives for optimal activation of anabolic and myogenic mechanisms to increase myofiber size. Clearly, activation of these mechanisms must precede skeletal muscle growth. Most mechanistic studies of RE have involved analysis of outcome variables after many training sessions. This study measured molecular level responses to RE on a scale of hours to establish a time course for the activation of myogenic mechanisms. Muscle biopsy samples were collected from nine subjects before and after acute bouts of RE. The response to a single bout was assessed at 12 and 24 h postexercise. Further samples were obtained 24 and 72 h after a second exercise bout. RE was induced by neuromuscular electrical stimulation to generate maximal isometric contractions in the muscle of interest. A single RE bout resulted in increased levels of mRNA for IGF binding protein-4 (84%), MyoD (83%), myogenin (approximately 3-fold), cyclin D1 (50%), and p21-Waf1 (16-fold), and a transient decrease in IGF-I mRNA (46%). A temporally conserved, significant correlation between myogenin and p21 mRNA was observed (r = 0.70, P < or = 0.02). The mRNAs for mechano-growth factor, IGF binding protein-5, and the IGF-I receptor were unchanged by RE. Total skeletal muscle RNA was increased 72 h after the second serial bout of RE. These results indicate that molecular adaptations of skeletal muscle to loading respond in a very short time. This approach should provide insights on the mechanisms that modulate adaptation to RE and may be useful in evaluating RE training protocol variables with high temporal resolution.     

Effect of training on the GH/IGF-I axis during exercise in middle-aged men: relationship to glucose homeostasis

The aim of this study was to compare circulating levels of growth hormone (GH), IGF-I, and IGF-binding protein (IGFBP)-1 and IGFBP-3 in response to a long-duration endurance exercise in trained vs. sedentary middle-aged males and to determine whether a relationship with glucose homeostasis exists. Seven trained men (Tr) were compared with seven age-matched sedentary men (Sed) during two trials of 60 min of cycling exercise performed below (-VT) and above (+VT) the ventilatory threshold. Insulin sensitivity (S(I)) was higher in Tr than in Sed (P < 0.001). Basal GH, IGF-I, and IGFBP-1 and -3 were higher in Tr (P < 0.05). During +VT, Tr had a threefold higher GH response, whereas their blood glucose level was better maintained (P < 0.05). Basal IGFBP-1 was correlated with S(I) (P < 0.01). These data indicate that endurance training in middle-aged men increased the activity of the GH/IGF-I system and improved glucoregulation both at rest and during high-intensity endurance exercise.     

Effect of pulsatile growth hormone administration to the growth-restricted fetal sheep on somatotrophic axis gene expression in fetal and placental tissues

We have previously reported (Bauer MK, Breier BH, Bloomfield FH, Jensen EC, Gluckman PD, and Harding JE. J Endocrinol 177: 83-92, 2003) that a chronic pulsatile infusion of growth hormone (GH) to intrauterine growth-restricted (IUGR) ovine fetuses increased fetal circulating IGF-I levels without increasing fetal growth. We hypothesized a cortisol-induced upregulation of fetal hepatic GH receptor (GH-R) mRNA levels, secondary increases in IGF-I mRNA levels, and circulating IGF-I levels, but a downregulation of the type I IGF receptor (IGF-IR) as an explanation. We, therefore, measured mRNA levels of genes of the somatotrophic axis by real-time RT-PCR in fetal and placental tissues of fetuses with IUGR (induced by uteroplacental embolization from 110- to 116-days gestation) that received either a pulsatile infusion of GH (total dose 3.5 mg/day) or vehicle from 117-126 days and in control fetuses (n = 5 per group). Tissues were collected at 127 days (term, 145 days). Fetal cortisol concentrations were significantly increased in IUGR fetuses. However, in liver, GH-R, but not IGF-I or IGF-IR, mRNA levels were decreased in both IUGR groups. In contrast, in placenta, GH-R, IGF-I, and IGF-IR expression were increased in IUGR vehicle-infused fetuses. GH infusion further increased placental GH-R and IGF-IR, but abolished the increase in IGF-I mRNA levels. GH infusion reduced IGF-I expression in muscle and increased GH-R but decreased IGF-IR expression in kidney. IUGR increased hepatic IGF-binding protein (IGFBP)-1 and placental IGFBP-2 and -3 mRNA levels with no further effect of GH infusion. In conclusion, the modest increases in circulating cortisol concentrations in IUGR fetuses did not increase hepatic GH-R mRNA expression and, therefore, do not explain the increased circulating IGF-I levels that we found with GH infusion, which are likely due to reduced clearance rather than increased production. We demonstrate tissue-specific regulation of the somatotrophic axis in IUGR fetuses and a discontinuity between GH-R and IGF-I gene expression in GH-infused fetuses that is not explained by alterations in phosphorylated STAT5b.     

Effect of single wrist exercise on fibroblast growth factor-2, insulin-like growth factor, and growth hormone

Anabolic effects of exercise are mediated, in part, by fibroblast growth factor-2 (FGF-2), insulin-like growth factor-I (IGF-I), and growth hormone (GH). To identify local vs. systemic modification of these mediators, 10 male subjects performed 10 min of unilateral wrist-flexion exercise. Blood was sampled from catheters placed in basilic veins of both arms. Lactate was significantly increased only in the exercising arm. FGF-2 decreased dramatically (P < 0.01) in both the resting (from 1.49 +/- 0.32 to nadir at 0.11 +/- 0.11 pg/ml) and exercising arm (1.80 +/- 0.60 to 0.29 +/- 0.14 pg/ml). Small but significant increases were found in both the resting and exercising arm for IGF-I and IGF binding protein-3 (IGFBP-3). GH was elevated in blood sampled from both the resting (from 1.04 +/- 0.68 to a peak of 2.57 +/- 0.53 ng/ml) and exercising arm (1.04 +/- 0.66 to 2.43 +/- 0.42 ng/ml, P < 0.05). Unilateral wrist exercise was not sufficiently intense to increase circulating lactate or heart rate, but it led to systemic changes in GH, IGF-I, IGFBP-3, and FGF-2. Low-intensity exercise involving small muscle groups can influence the circulating levels of growth factors.     

Constitutive pro- and anti-inflammatory cytokine and growth factor response to exercise in leukocytes.

Leukocytosis following exercise is a well-described phenomenon of stress/inflammatory activation in healthy humans. We hypothesized that, despite this increase in circulating inflammatory cells, exercise would paradoxically induce expression of both pro- and anti-inflammatory cytokines and growth factors within these cells. To test this hypothesis, 11 healthy adult men, 18-30 yr old, performed a 30-min bout of heavy cycling exercise; blood sampling was at baseline, end-exercise, and 60 min into recovery. The percentage of leukocytes positive for intracellular cytokines and growth factors and mean fluorescence intensity was obtained by flow cytometry. Proinflammatory cytokines (IL-1alpha, IL-2, IFN-gamma, and TNF-alpha), a pleiotropic cytokine (IL-6), and anti-inflammatory cytokines and growth factors [IL-4, IL-10, growth hormone (GH), and IGF-I] were examined. Median fluorescence intensity was not affected by exercise; however, we found a number of significant changes (P < 0.05 by mixed linear model and modified t-test) in the numbers of circulating cells positive for particular mediators. The pattern of expression reflected both pro- and anti-inflammatory functions. In T-helper lymphocytes, TNF-alpha, but also IL-6, and IL-4 were significantly increased. In monocytes, both IFN-gamma and IL-4 increased. B-lymphocytes positive for GH and IGF-I increased significantly. GH-positive granulocytes also significantly increased. Collectively, these observations indicate that exercise primes an array of pro- and anti-inflammatory and growth factor expression within circulating leukocytes, perhaps preparing the organism to effectively respond to a variety of stressors imposed by exercise.     

Skeletal muscle capillarity and angiogenic mRNA levels after exercise training in normoxia and chronic hypoxia.

Gene expression of vascular endothelial growth factor (VEGF), and to a lesser extent of transforming growth factor-beta(1) (TGF-beta(1)) and basic fibroblast growth factor (bFGF), has been found to increase in rat skeletal muscle after a single exercise bout. In addition, acute hypoxia augments the VEGF mRNA response to exercise, which suggests that, if VEGF is important in muscle angiogenesis, hypoxic training might produce greater capillary growth than normoxic training. Therefore, we examined the effects of exercise training (treadmill running at the same absolute intensity) in normoxia and hypoxia (inspired O(2) fraction = 0.12) on rat skeletal muscle capillarity and on resting and postexercise gene expression of VEGF, its major receptors (flt-1 and flk-1), TGF-beta(1), and bFGF. Normoxic training did not alter basal or exercise-induced VEGF mRNA levels but produced a modest twofold increase in bFGF mRNA (P < 0.05). Rats trained in hypoxia exhibited an attenuated VEGF mRNA response to exercise (1.8-fold compared 3.4-fold with normoxic training; P < 0.05), absent TGF-beta(1) and flt-1 mRNA responses to exercise, and an approximately threefold (P < 0.05) decrease in bFGF mRNA levels. flk-1 mRNA levels were not significantly altered by either normoxic or hypoxic training. An increase in skeletal muscle capillarity was observed only in hypoxically trained rats. These data show that, whereas training in hypoxia potentiates the adaptive angiogenic response of skeletal muscle to a given absolute intensity of exercise, this was not evident in the gene expression of VEGF or its receptors when assessed at the end of training.     

Long-term monitoring of insulin-like growth factor I in adult growth hormone deficiency: a critical appraisal

Serum insulin-like growth factor I (IGF-I) levels predominantly reflect the hepatic effect of growth hormone (GH). Compared with serum GH levels, which reflect pulsatile GH secretion, serum IGF-I levels exhibit no major diurnal variation and thus provide a better estimate of integrated GH secretion in an individual patient. Measurement of serum IGF-I levels allows reliable identification of states of GH excess. In contrast, in a large proportion of adults with severe GH deficiency, serum IGF-I levels are within the normal range. Serum IGF-I levels increase markedly in response to GH administration and are often used as a surrogate variable for overall responsiveness to such treatment. Current data, however, suggest a poor relationship between changes in or levels of IGF-I and efficacy variables such as body composition, muscle function and well-being. The use of serum IGF-I as a guide during dose titration in the initial phase of treatment and during long-term monitoring of GH replacement therapy in adults, and its use as a safety marker or predictor of future morbidity and mortality are discussed here.     

IGF-I has no effect on postexercise suppression of the ubiquitin-proteasome system in rat skeletal muscle.

Both exercise and insulin-like growth factor I (IGF-I) are known to have major hypertrophic effects in skeletal muscle; however, the interactive effect of exogenous IGF-I and exercise on muscle protein turnover or the ubiquitin-proteasome pathway has not been reported. In the present study, we have examined the interaction between endurance exercise training and IGF-I treatment on muscle protein turnover and the ubiquitin-proteasome pathway in the postexercise period. Adult male rats (270-280 g) were randomized to receive 5 consecutive days of progressive treadmill exercise and/or IGF-I treatment (1 mg. kg body wt(-1). day(-1)). Twenty-four hours after the last bout of exercise, the rate of protein breakdown in incubated muscles was significantly reduced compared with that in unexercised rats. This was associated with a significant reduction in the chymotrypsin-like activity of the proteasome and the rate of ubiquitin-proteasome-dependent casein hydrolysis in muscle extracts from exercised compared with unexercised rats. In contrast, the muscle expression of the 20S proteasome subunit beta-1, ubiquitin, and the 14-kDa E2 ubiquitin-conjugating enzyme was not altered by exercise or IGF-I treatment 24 h postexercise. Exercise had no effect on the rates of total mixed muscle protein synthesis in incubated muscles 24 h postexercise. IGF-I treatment had no effect on muscle weights or the rates of protein turnover 24 h after endurance exercise. These results suggest that a suppression of the ubiquitin-proteasome proteolytic pathway after endurance exercise may contribute to the acute postexercise net protein gain.     

Resistance exercise alters MRF and IGF-I mRNA content in human skeletal muscle.

Increasing evidence suggests that the myogenic regulatory factors (MRFs) and IGF-I have important roles in the hypertrophy response observed after mechanical loading. We, therefore, hypothesized that a bout of heavy-resistance training would affect the MRF and IGF-I mRNA levels in human skeletal muscle. Six male subjects completed four sets of 6-12 repetitions on a leg press and knee extensor machine separated by 3 min. Myogenin, MRF4, MyoD, IGF-IEabc (isoforms a, b, and c) and IGF-IEbc (isoform b and c) mRNA levels were determined in the vastus lateralis muscle by RT-PCR before exercise, immediately after, and 1, 2, 6, 24, and 48 h postexercise. Myogenin, MyoD, and MRF4 mRNA levels were elevated (P < 0.005) by 100-400% 0-24 h postexercise. IGF-IEabc mRNA content decreased (P < 0.005) by approximately 44% after 1 and 6 h of recovery. The IGF-IEbc mRNA level was unaffected. The present study shows that myogenin, MyoD, and MRF4 mRNA levels are transiently elevated in human skeletal muscle after a single bout of heavy-resistance training, supporting the idea that the MRFs may be involved in regulating hypertrophy and/or fiber-type transitions. The results also suggest that IGF-IEa expression may be downregulated at the mRNA level during the initial part of recovery from resistance exercise.     

Effects of acute exercise, exercise training, and diabetes on the expression of lymphangiogenic growth factors and lymphatic vessels in skeletal muscle

Blood and lymphatic vessels together form the circulatory system, allowing the passage of fluids and molecules within the body. Recently we showed that lymphatic capillaries are also found in the capillary bed of skeletal muscle. Exercise is known to induce angiogenesis in skeletal muscle, but it is not known whether exercise has effects on lymphangiogenesis or lymphangiogenic growth factors. We studied lymphatic vessel density and expression of the main lymphangiogenic growth factors VEGF-C and VEGF-D and their receptor VEGFR-3 in response to acute running exercise and endurance exercise training in the skeletal muscle of healthy and diabetic mice. VEGF-C mRNA expression increased after the acute exercise bout (P < 0.05) in healthy muscles, but there was no change in diabetic muscles. VEGF-C levels were not changed either in healthy or in diabetic muscle after the exercise training. Neither acute exercise nor exercise training had an effect on the mRNA expression of VEGF-D or VEGFR-3 in healthy or diabetic muscles. Lymphatic vessel density was similar in sedentary and trained mice and was >10-fold smaller than blood capillary density. Diabetes increased the mRNA expression of VEGF-D (P < 0.01). Increased immunohistochemical staining of VEGF-D was found in degenerative muscle fibers in the diabetic mice. In conclusion, the results suggest that acute exercise or exercise training does not significantly affect lymphangiogenesis in skeletal muscle. Diabetes increased the expression of VEGF-D in skeletal muscle, and this increase may be related to muscle fiber damage.     

Effect of GH on human skeletal muscle lipid metabolism in GH deficiency

Adult-onset growth hormone (GH) deficiency (GHD) is associated with insulin resistance and decreased exercise capacity. Intramyocellular lipids (IMCL) depend on training status, diet, and insulin sensitivity. Using magnetic resonance spectroscopy, we studied IMCL content following physical activity (IMCL-depleted) and high-fat diet (IMCL-repleted) in 15 patients with GHD before and after 4 mo of GH replacement therapy (GHRT) and in 11 healthy control subjects. Measurements of insulin resistance and exercise capacity were performed and skeletal muscle biopsies were carried out to assess expression of mRNA of key enzymes involved in skeletal muscle lipid metabolism by real-time PCR and ultrastructure by electron microscopy. Compared with control subjects, patients with GHD showed significantly higher difference between IMCL-depleted and IMCL-repleted. GHRT resulted in an increase in skeletal muscle mRNA expression of IGF-I, hormone-sensitive lipase, and a tendency for an increase in fatty acid binding protein-3. Electron microscopy examination did not reveal significant differences after GHRT. In conclusion, variation of IMCL may be increased in patients with GHD compared with healthy control subjects. Qualitative changes within the skeletal muscle (i.e., an increase in free fatty acids availability from systemic and/or local sources) may contribute to the increase in insulin resistance and possibly to the improvement of exercise capacity after GHRT. The upregulation of IGF-I mRNA suggests a paracrine/autocrine role of IGF-I on skeletal muscle.     

Effect of rhIL-6 infusion on GH-->IGF-I axis mediators in humans

Exercise leads to simultaneous increases in mediators signaling apparently antagonistic functional responses such as growth factors and inflammatory mediators. The aim of the present study was to demonstrate the physiological effect of IL-6 on circulating components of the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis. Twelve men (ages 26 +/- 2 yr) were divided into two groups (n = 6 in each group), receiving either albumin or recombinant human (rh) IL-6 infusion. IL-6 was infused via an antecubital vein, and a contralateral antecubital vein was used for blood sampling. The IL-6 dose was chosen to reach plasma levels of IL-6 characteristic of intense exercise (5 microg/h, for 3 h, resulting in plasma levels of 100 pg/ml). Blood samples for GH, GH binding protein, IGF-I, and IGF binding protein (IGFBP)-1 and -3 were collected at baseline, 30 min, and 1, 2, 3, 4, 5, and 8 h after the beginning of the rhIL-6 infusion. IL-6 levels increased only in the rhIL-6-infused group (P < 0.0005) and returned to baseline after the infusion was stopped. IL-6 infusion led to a significant increase in GH, peaking 1 h after the beginning of infusion (P < 0.001). A decrease in total IGF-I levels was noted only in the rhIL-6-infused group (P < 0.027). An initial decrease in IGFBP-1 levels was noted in both groups during infusion (P < 0.03). Following the initial decrease, there was a significant increase in IGFBP-1 levels only in the IL-6-infused participants, peaking at 2 after the infusion cessation (P < 0.001). IL-6 infusion had no effect on GH binding protein, IGFBP-3, and acid-labile subunit levels. rhIL-6 levels similar to the levels found after strenuous exercise induced a typical exercise-associated GH-->IGF-I axis response (increase GH, decreased IGF-I, and elevated IGFBP-1). The results suggest that IL-6 plays a role in the GH-->IGF-I response to intense exercise.     

The role of the GH/IGF-I axis for cardiac function and structure.

There is ample evidence to support a role for the GH/IGF-I axis in regulation of cardiac growth, structure and function. GH may act directly on the heart or through circulating IGF-I (Fig. 1). Moreover, GH has been found to regulate local production of IGF-I in the heart. Both the GH-R and IGF-I-R are expressed in cardiac tissue. Hence, the IGF-I-R receptor can theoretically be activated through locally produced IGF-I acting via autocrine/paracrine mechanisms, or via circulating IGF-I exerting its effects as an endocrine agent. During conditions of pressure and volume overload, an increased systolic wall stress triggers an induction of gene expression of IGF-I GH-R and possibly IGF-J-R implying a potential role for the GH/IGF-I axis in the development of adaptive hypertrophy of the heart and vessels. Cardiovascular effects of GH in clinical studies include beneficial effects on contractility, exercise performance and TPR, and experimental studies suggest an increased Ca2+ responsiveness as one possible underlying cause, although effects of GH and IGF-I on apoptosis may possibly also play a role. The GH secretagogue hexarelin improves cardiac function after experimental myocardial infarction either through an increased GH secretion or possibly through a cardiac GHS receptor, although this needs further investigation. Moreover, it is clear that further basic and clinical studies are required to gain insight into the GH and IGF-I mechanisms of action and to monitor long-term effects when GH is administered as substitution therapy or as an agent in the treatment of congestive heart failure.     

Androgen receptors and testosterone in men--effects of protein ingestion, resistance exercise and fiber type

The purpose of this study was to examine the impact of protein ingestion on circulating testosterone and muscle androgen receptor (AR) as well as on insulin-like growth factor-I (MGF and IGF-IEa) responses to a resistance exercise (RE) bout in (57-72 year) men. Protein (15 g whey) (n=9) or placebo (n=9) was consumed before and after a RE bout (5 sets of 10 repetition maximums), and vastus lateralis muscle biopsies were taken pre, 1 and 48 h post-RE. The protein ingestion blunted the RE-induced increase in serum free and total testosterone while the RE bout significantly increased muscle AR mRNA levels in older men (P<0.05). However, protein ingestion did not significantly affect AR mRNA or protein expression, or MGF and IGF-IEa mRNA expression at 1 and 48 h post-RE. Immunohistochemical staining of muscle cross-sections was done with antibodies specific to AR and MyHC I and II and showed that there seems to be within or near the type-I muscle fibers a greater staining of ARs than within or near the type-II fibres. In conclusion, the protein ingestion hinders RE-induced increase in serum testosterone in older men but may not significantly affect muscle AR, MGF or IGF-IEa gene expression. Furthermore, the present study shows that even older men are able to increase muscle AR mRNA expression in response to a RE bout.     

Plasma ghrelin levels in rainbow trout in response to fasting, feeding and food composition, and effects of ghrelin on voluntary food intake

Ghrelin, a peptide hormone which stimulates growth hormone (GH) release, appetite and adiposity in mammals, was recently identified in fish. In this study, the roles of ghrelin in regulating food intake and the growth hormone (GH)-insulin-like growth factor I (IGF-I) system of rainbow trout (Oncorhynchus mykiss) were investigated in three experiments: 1) Pre- and postprandial plasma levels of ghrelin were measured in relation to dietary composition and food intake through dietary inclusion of radio-dense lead-glass beads, 2) the effect of a single intraperitoneal (i.p.) injection with rainbow trout ghrelin on short-term voluntary food intake was examined and 3) the effect of one to three weeks fasting on circulating ghrelin levels and the correlation with plasma GH and IGF-I levels, growth and lipid content in the liver and muscle was studied. There was no postprandial change in plasma ghrelin levels. Fish fed a normal-protein/high-lipid (31.4%) diet tended to have higher plasma ghrelin levels than those fed a high-protein/low-lipid (14.1%) diet. Plasma ghrelin levels decreased during fasting and correlated positively with specific growth rates, condition factor, liver and muscle lipid content, and negatively with plasma GH and IGF-I levels. An i.p. ghrelin injection did not affect food intake during 12-hours post-injection. It is concluded that ghrelin release in rainbow trout may be influenced by long-term energy status, and possibly by diet composition. Further, in rainbow trout, ghrelin seems to be linked to growth and metabolism, but does not seem to stimulate short-term appetite through a peripheral action.     

Bioassayable growth hormone release in rats in response to a single bout of treadmill exercise.

Plasma growth hormone (GH) measured by immunoassay [immunoassayable GH (IGH)] and by tibial bioassay [bioassayable GH (BGH)] increases in humans in response to exercise. In rats, however, IGH does not change in response to exercise. The objective of this study was to determine the BGH response to an acute exercise bout in rats. The rats ran on a treadmill at a rate of 27 m/min for 15 min, after which plasma and pituitary hormones, including IGH and BGH, and plasma metabolites were measured. Plasma and pituitary IGH were unchanged from control groups after the acute exercise bout, whereas plasma BGH was increased by 300% and pituitary BGH was decreased by 50%. Plasma thyroxine and corticosterone levels were significantly increased after a single exercise bout, but plasma testosterone, 3,5, 3'-triiodothyronine, glucose, lactate, and triglyceride concentrations were unchanged. Given previous results from in situ nerve stimulation studies (Gosselink KL, Grindeland RE, Roy RR, Zhong H, Bigbee AJ, Grossman EJ, and Edgerton VR. J Appl Physiol 84: 1425-1430, 1998), these in vivo results are consistent with the rapid BGH response during exercise being induced by the activation of muscle afferents.     

Effect of exercise, training, and glycogen availability on IL-6 receptor expression in human skeletal muscle.

The cytokine interleukin-6 (IL-6) exerts it actions via the IL-6 receptor (IL-6R) in conjunction with the ubiquitously expressed gp130 receptor. IL-6 is tightly regulated in response to exercise, being affected by factors such as exercise intensity and duration, as well as energy availability. Although the IL-6 response to exercise has been extensively studied, little is known about the regulation of the IL-6R response. In the present study, we aimed to investigate the effect of exercise, training, and glycogen availability, factors known to affect IL-6, on the regulation of gene expression of the IL-6R in human skeletal muscle. Human subjects performed either 10 wk of training with an acute exercise bout before and after the training period, or a low-glycogen vs. normal-glycogen acute exercise trial. The IL-6R mRNA response was evaluated in both trials. In response to acute exercise, an increase in IL-6R mRNA levels was observed. Neither training nor intramuscular glycogen levels had an effect on the IL-6R mRNA response to exercise. However, after 10 wk of training, the skeletal muscle expressed a higher mRNA level of IL-6R compared with before training. The present study demonstrated that the IL-6R gene expression levels in skeletal muscle are increased in response to acute exercise, a response that is very well conserved, being affected by neither training status nor intramuscular glycogen levels, as opposed to IL-6. However, after the training period, IL-6R mRNA production was increased in skeletal muscle, suggesting a sensitization of skeletal muscle to IL-6 at rest.