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Exercise training efficiency depends on the intensity, volume, duration, and frequency of training, as well as on the athlete's ability to tolerate it. Recent efforts to quantify the effects of aerobic exercise training on hormonal response have suggested that exercise leads to simultaneous changes of antagonistic mediators. The effects of anaerobic exercise on these mediators are not known. Therefore, the aim of the present study was to evaluate the effects of a brief sprint interval session on the balance between anabolic (growth hormone [GH]--> insulin-like growth factor [IGF]-I axis) and catabolic hormones (cortisol), and circulating inflammatory cytokines such as interleukin (IL)-6. Twelve healthy elite junior handball players (17-20 years) participated in the study. Exercise consisted of a 4 x 250-m run on a treadmill, at a constant intensity of 80% of the personal maximal speed. Each run was separated by 3 minutes of rest. Blood samples were collected before, immediately after each 250-m run, and 1 hour after the last run. Exercise led to significant increases in GH (0.3 +/- 0.2 to 5.1 +/- 2.2 ngxml, p < 0.05), IGF binding protein (IGFBP)-3 (4191 +/- 2.48 to 4875 +/- 301 ngxml, p < 0.05), IL-6 (1.3 +/- 0.2 to 2.1 +/- 0.3 pgxml, p < 0.002), testosterone, and testosterone/cortisol ratio, and to a significant decrease in IGFBP-1 levels. Levels of IL-6 remained elevated 1 hour after the end of exercise. Exercise had no significant effects on IGF-I and cortisol levels. Changes in the GH-IGF-I axis and testosterone/cortisol ratio after the brief sprint interval exercise suggested exercise-related anabolic adaptations. The increase in IL-6 may indicate its important role in muscle tissue repair after anaerobic exercise. Changes in the anabolic-catabolic hormonal balance and in inflammatory mediators can be used as an objective tool to gauge the training intensity of different types of anaerobic exercises and training periods.

Background: Crohn’s disease (CD) and ulcerative colitis (UC) are chronic, immune-mediated inflammatory bowel diseases (IBD) affecting millions of people worldwide. IBD therapies, designed for continuous immune suppression, often render patients more susceptible to infections. The effect of the immune suppression on the risk of coronavirus disease-19 (COVID-19) is not fully determined yet. Objective: To describe COVID-19 characteristics and outcomes and to evaluate the association between IBD phenotypes, infection outcomes and immunomodulatory therapies. Methods: In this multi-center study, we prospectively followed IBD patients with proven COVID-19. De-identified data from medical charts were collected including age, gender, IBD type, IBD clinical activity, IBD treatments, comorbidities, symptoms and outcomes of COVID-19. A multivariable regression model was used to examine the effect of immunosuppressant drugs on the risk of infection by COVID-19 and the outcomes. Results: Of 144 IBD patients, 104 (72%) were CD and 40 (28%) were UC. Mean age was 32.2 ± 12.6 years. No mortalities were reported. In total, 94 patients (65.3%) received biologic therapy. Of them, 51 (54%) at escalated doses, 10 (11%) in combination with immunomodulators and 9 (10%) with concomitant corticosteroids. Disease location, behavior and activity did not correlate with the severity of COVID-19. Biologics as monotherapy or with immunomodulators or corticosteroids were not associated with more severe infection. On the contrary, patients receiving biologics had significantly milder infection course (p = 0.001) and were less likely to be hospitalized (p = 0.001). Treatment was postponed in 34.7% of patients until recovery from COVID-19, without consequent exacerbation. Conclusion: We did not witness aggravated COVID-19 outcomes in patients with IBD. Patients treated with biologics had a favorable outcome.

PurposePhysical inactivity is deleterious to health, but it has been difficult to determine the extent to which these effects are attributable to abnormal body composition or to factors related to physical activity alone. To begin to gauge independent effects of physical activity on health risk, we matched by BMI two groups of normal-weight adolescent females, one physically active (all participants in high school sports), and one sedentary.MethodsThirty-seven sedentary and 37 physically active adolescent females (mean 15.5 yr) were matched for age and BMI percentile (mean = 58.8). Comparisons included fitness, body composition and bone mineralization (by DEXA), circulating inflammatory cytokines, growth factors, bone-turnover markers, leptin, and adiponectin.ResultsCompared with the normal-weight sedentary girls, active girls had significantly (P < 0.05) higher fitness level (peak VO2 35.5 +/- 5.2 vs 24.4 +/- 4.1 mL.kg(-1).min(-1)), lean body mass (43.2 +/- 4.4 vs 38.7 +/- 3.6 kg), bone mineralization (spinal BMD z-scores 0.04 +/- 0.88 vs -0.41 +/- 0.85), and lower percent body fat (25.4 +/- 04.6 vs 29.7 +/- 03.7%). Additionally, active girls had lower inflammatory cytokines levels (e.g., TNF-alpha 1.7 +/- 1.3 vs 2.6 +/- 2.2 pg.mL(-1)), and leptin (17.4 +/- 11.2 vs 24.7 +/- 14.7 ng.mL(-1)), and higher bone-turnover markers (e.g. osteocalcin 12.6 +/- 7.6 vs 7.8 +/- 3.0 U.L(-1)), IGFBP-3 (6416 +/- 21280 vs 4247 +/- 1082 ng.mL(-1)), and adiponectin levels (11919 +/- 3935 vs 9305 +/- 2843 ng.mL(-1)).ConclusionThe normal-weight, physically active group was fitter and had greater lean body mass, stronger bones, and lower levels of inflammatory markers than did the normal-weight, sedentary group. In adolescent girls, the choice of a lifestyle involving high school sports is characterized by a circulating mediator and body composition pattern that, if sustained, is associated with generally lower long-term risk of cardiovascular disease and osteoporosis.

BackgroundObesity modifies inflammatory mediators, but little is known about how obesity modifies the inflammatory responses of exercising children. This study assessed the acute effect of exercise on inflammatory mediators in overweight children.MethodsTwenty-eight overweight (OW) youth (body mass index > 85%) and 30 normal-weight (NW) controls of the same proportions of age and gender performed 10 2-minute bouts of cycle ergometry exercise above the anaerobic threshold, with 1-minute rest intervals between bouts. Pre- and postexercise blood samples were collected for white blood cell subpopulation and inflammatory cytokines.ResultsBaseline leukocyte populations were higher in OW youth (p < .05). Exercise increased most leukocyte subtypes for both groups (p < .05). Granulocytes remained elevated 2 hours postexercise (p < .05) for both groups, whereas monocytes remained elevated 2 hours postexercise for the OW children. Natural killer (NK) cells dropped below baseline 2 hours postexercise. Exercise significantly decreased CD4 and CD8 cells, which remained depressed 2 hours postexercise in the OW children. Baseline levels of interleukin (IL)-6 were congruent approximately 64% higher in OW children (p < .001). Exercise increased IL-6 in both groups (p < .001), which further increased 2 hours postexercise (p < .05). Tumor necrosis factor alpha, IL-1beta, and IL-1 receptor antagonist did not change with exercise.ConclusionsElevated baseline leukocyte subtypes and IL-6 levels in OW children suggest that childhood obesity is associated with a chronic low-grade inflammatory state. The acute inflammatory response to intense exercise appears to be similar between NW and OW children for most markers, but the depression of NK, CD4, and CD8 cells 2 hours postexercise suggests that an acute risk of mitogen-induced inflammation may exist in OW children after high-intensity exercise.

We tested the hypothesis that exercise could stimulate CD34+ peripheral blood hematopoietic stem cells (PBSC) in children. Fourteen early pubertal boys (EP, age 10.3 +/- 0.3 y) and 13 late pubertal boys (LP, age 16.5 +/- 0.4 y) performed 20 min of moderate-to-vigorous cycle ergometer exercise. Blood was drawn before and after exercise. Cells were stained for surface CD34+. Plasma granulocyte colony stimulating factor (G-CSF), Fms-like tyrosine kinase-3 (FLT-3), and stromal cell-derived factor-1 (SDF-1) were measured using ELISA. Exercise substantially increased PBSC (in EP from 112 +/- 21 to 182 +/- 30 cells/microL, p=0.0007; in LP from 63 +/- 8 to 152 +/- 21, p=0.0008), and to a smaller extent FLT-3 (in EP from 98 +/- 5 to 110 +/- 6 pg/mL, p

BackgroundMany female adolescents participate in insufficient physical activity to maintain cardiovascular fitness and promote optimal bone growth. This study evaluates the impact of a school-based intervention on fitness, activity, and bone among adolescent females.MethodsSubjects were assigned to an intervention (n = 63) or comparison (n = 59) group, and underwent assessments of cardiovascular fitness (VO2peak), physical activity, body composition, bone mineral density (BMD), bone mineral content (BMC), and serum markers of bone turnover at baseline and at the end of each of two school semesters.ResultsThe intervention increased physical activity, VO2peak, and BMC for the thoracic spine (P values < 0.05). Bone turnover markers were not affected. In longitudinal analyses of the combined groups, improvements in cardiovascular fitness predicted increased bone formation (P < 0.01) and bone resorption (P < 0.05).ConclusionA school-based intervention for adolescent females effectively increased physical activity, cardiovascular fitness, and thoracic spine BMC.

Background and Aims Home self-injection of the human anti-tumour necrosis alpha [anti-TNFα] monoclonal adalimumab complicates prospective serial-sampling studies. Although a recent study examined adalimumab levels and immunogenicity in Crohn's disease [CD] patients, prospective real-world data from ulcerative colitis [UC] patients are lacking. Methods A three-monthly home-visit programme from induction was established prospectively for UC patients. Clinical scores were determined at each visit, and sera were obtained for assessment of drug and anti-adalimumab antibody levels. Calprotectin was measured using a smartphone-based app. This cohort was compared to a parallel prospective cohort of adalimumab-treated CD patients [POETIC1]. Results Fifty UC patients starting adalimumab [median follow-up 28 weeks] were compared to 98 adalimumab-treated CD patients [median follow-up 44 weeks]. Only 11/50 UC patients [22%] continued treatment to the end of the follow-up compared with 50/98 [51%] CD patients (odds ratio [OR] = 0.27, p  = 0.001). Loss of response was significantly more common in UC patients [OR = 3.2, p  = 0.001]. Seventeen patients [34%] in the UC cohort developed anti-adalimumab antibodies, 9/17 [52.9%] as early as week 2. There was no difference between patient cohorts in the overall development of anti-adalimumab antibodies [34% vs 30.6%, respectively, OR = 1.67, p  = 0.67], nor was there a difference in early immunogenicity [OR = 1.39, p  = 0.35]. There was no difference in low drug levels [<3 µg/mL] between the two cohorts [OR = 0.87, p  = 0.83]. Conclusions Loss of response to adalimumab therapy was significantly more common in the UC compared to the CD cohort and was driven by a higher rate of non-immunogenic, pharmacodynamic parameters. [ABSTRACT FROM AUTHOR]

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.

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.

Under-nutrition impairs immune responses, but far less is known about the impact of over-nutrition, such as obesity, on the response to vaccines. We measured the effect of childhood overweight status on inflammatory mediators, circulating immunoglobulins and tetanus antibodies in fifteen overweight children (BMI > 85 age-adjusted percentile) and 15 age-matched normal weight controls. Fitness was measured by a progressive ramp type exercise test. Lean body mass (LBM) and fat mass were determined by DXA. Tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), interleukin-1 β (IL-1β) and interleukin-1 receptor antagonist (IL-1ra) were used to assess the inflammatory status; and circulating immunoglobulins (IgM, IgA, IgG and IgG subclasses) and specific IgG titer to tetanus were used to assess humoral immunity. Overweight children had higher LBM and percent fat mass, and lower peak VO2 normalized to body weight. IL-6 was significantly higher in the obese children (2.6 ± 0.3 vs. 1.3 ± 0.3 pg/ml, in overweight and normal weight children, respectively; p < 0.05). No significant differences were found in TNF-a, IL-1β and IL-1ra between the groups. No significant differences were found in immunoglobulin levels (IgM, IgA, IgG and IgG subclasses) between the groups. Anti-tetanus IgG antibodies were significantly lower in the overweight children compared to normal weight controls (2.4 ± 0.6 vs 4.2 ± 0.5 IU/ml, in overweight and normal weight children, respectively; p < 0.05). The reduced specific antibody response to tetanus in obese children and adolescent might be du to mechanical factors such as lower relative vaccination dose, or reduced absorption from the injection site due to increased adipose tissue, or related to reduce immune response due to chronic low grade inflammation expressed by the higher levels of IL-6.

Obesity blunts catecholamine and growth hormone (GH) responses to exercise in adults, but the effect of obesity on these exercise-associated hormonal responses in children is unclear. Therefore, the aim of the present study was to asses the effect of childhood obesity on the counterregulatory hormonal response to acute exercise. Twenty-five obese children (Ob; body mass index > 95%), and 25 age, gender, and maturity-matched normal-weight controls (NW) participated in the study. Exercise consisted of ten 2-min bouts of constant-cycle ergometry above the anaerobic threshold, with 1-min rest intervals between each bout. Pre-, post-, and 120-min postexercise blood samples were collected for circulating components of the GH-IGF-I axis and catecholamines. There were no differences in peak exercise heart rate, serum lactate, and peak O2 uptake normalized to lean body mass between the groups. Obesity attenuated the GH response to exercise (8.9 +/- 1.1 vs. 3.4 +/- 0.7 ng/ml in NW and Ob participants, respectively; P < 0.02). No significant differences in the response to exercise were found for other components of the GH-IGF-I axis. Obesity attenuated the catecholamine response to exercise (epinephrine: 52.5 +/- 12.7 vs. 18.7 +/- 3.7 pg/ml, P < 0.02; norepinephrine: 479.5 +/- 109.9 vs. 218.0 +/- 26.0 pg/ml, P < 0.04; dopamine: 17.2 +/- 2.9 vs. 3.5 +/- 1.9 pg/ml, P < 0.006 in NW and Ob, respectively). Insulin levels were significantly higher in the obese children and dropped significantly after exercise in both groups. Despite the elevated insulin levels and the blunted counterregulatory response, none of the participants developed hypoglycemia. Childhood obesity was associated with attenuated GH and catecholamine response to acute exercise. These abnormalities were compensated for, so that exercise was not associated with hypoglycemia, despite increased insulin levels in obese children.

Under-nutrition impairs immune responses, but far less is known about the impact of over-nutrition, such as obesity, on the response to vaccines. We measured the effect of childhood overweight status on inflammatory mediators, circulating immunoglobulins and tetanus antibodies in fifteen overweight children (BMI > 85 age-adjusted percentile) and 15 age-matched normal weight controls. Fitness was measured by a progressive ramp type exercise test. Lean body mass (LBM) and fat mass were determined by DXA. Tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), interleukin-1 beta (IL-1beta) and interleukin-1 receptor antagonist (IL-1ra) were used to assess the inflammatory status; and circulating immunoglobulins (IgM, IgA, IgG and IgG subclasses) and specific IgG titer to tetanus were used to assess humoral immunity. Overweight children had higher LBM and percent fat mass, and lower peak VO2 normalized to body weight. IL-6 was significantly higher in the obese children (2.6 +/- 0.3 vs. 1.3 +/- 0.3 pg/ml, in overweight and normal weight children, respectively; p < 0.05). No significant differences were found in TNF-a, IL-1beta and IL-1ra between the groups. No significant differences were found in immunoglobulin levels (IgM, IgA, IgG and IgG subclasses) between the groups. Anti-tetanus IgG antibodies were significantly lower in the overweight children compared to normal weight controls (2.4 +/- 0.6 vs. 4.2 +/- 0.5 IU/ml, in overweight and normal weight children, respectively; p < 0.05). The reduced specific antibody response to tetanus in obese children and adolescent might be due to mechanical factors such as lower relative vaccination dose, or reduced absorption from the injection site due to increased adipose tissue, or related to reduce immune response due to the chronic low grade inflammation expressed by the higher levels of IL-6.

The reference evapotranspiration is an important agrometeorological parameter for planning and irrigation management and can be estimated by several methods. In the Brazilian Northeast, irregular and contingent water resources, studying evapotranspiration means optimizing irrigation management. This study aimed to analyze the influence of climate elements on the reference evapotranspiration calculated by the FAO-56 Penman-Monteith equation to the climatic elements of maximum and minimum temperature of the air, relative humidity, wind speed and insolation of a period of 53 Years, granted by INMET, of the city of Morada Nova in Ceará, whose climate according to the classification of Köppen is BSw'h '; Hot and semi-arid climate. The reference evapotranspiration was calculated according to the procedures suggested by FAO 56. The sensitivity analysis was based on the addition and decrease of one climatic element at a time in ± 5% up to the limit of ± 40% between -40% and -30% %, -20%, -15%, -10%, -5%, + 5%, + 10%, + 15%, + 20%, + 30% and + 40%, while maintaining the values of the other elements Constant. The results showed that the variation of the elements of the climate between dry and rainy season did not change the sensitivity of the Penmam-Monteith FAO 56 model to the evaluated climatic elements. The Penmam Motheith model, in the climatic conditions of Morada Nova, CE, is more sensitive to the elements of maximum temperature of the relative humidity of the air, followed by insolation, wind speed and minimum air temperature.

Several pathological conditions predict the use of glucocorticoids for the management of the inflammatory response; however, chronic or high dose glucocorticoid treatment is associated with hyperglycemia, hyperlipidemia, and insulin resistance and can be considered a risk factor for cardiovascular disease. Therefore, we investigated the mechanisms involved in the vascular responsiveness and inflammatory profile of mesenteric arteries of rats treated with high doses of glucocorticoids. Wistar rats were divided into a control (CO) group and a dexamethasone (DEX) group, that received dexamethasone for 7 days (2mg/kg/day, i.p.). Blood samples were used to assess the lipid profile and insulin tolerance. Vascular reactivity to Phenylephrine (Phe) and insulin, and O2•-production were evaluated. The intracellular insulin signaling pathway PI3K/AKT/eNOS and MAPK/ET-1 were investigated. Regarding the vascular inflammatory profile, TNF-α, IL-6, IL-1β and IL-18 were assessed. Dexamethasone-treated rats had decreased insulin tolerance test and endothelium-dependent vasodilation induced by insulin. eNOS inhibition caused vasoconstriction in the DEX group, which was abolished by the ET-A antagonist. Insulin-mediated relaxation in the DEX group was restored in the presence of the O2.- scavenger TIRON. Nevertheless, in the DEX group there was an increase in Phe-induced vasoconstriction. In addition, the intracellular insulin signaling pathway PI3K/AKT/eNOS was impaired, decreasing NO bioavailability. Regarding superoxide anion generation, there was an increase in the DEX group, and all measured proinflammatory cytokines were also augmented in the DEX group. In addition, the DEX-group presented an increase in low-density lipoprotein cholesterol (LDL-c) and total cholesterol (TC) and reduced high-density lipoprotein cholesterol (HDL-c) levels. In summary, treatment with high doses of dexamethasone promoted changes in insulin-induced vasodilation, through the reduction of NO bioavailability and an increase in vasoconstriction via ET-1 associated with generation of O2•- and proinflammatory cytokines.

We recently demonstrated that a brief endurance type training program led to increases in thigh muscle mass and peak oxygen uptake (VO(2)) in prepubertal girls. In this study, we examined the effect of training on the GH-->insulin-like growth factor I (GH-->IGF-I) axis, a system known to be involved both in the process of growth and development and in the response to exercise. Healthy girls (mean age 9.17 +/- 0.10 yr old) volunteered for the study and were randomized to control (n = 20) and training groups (n = 19) for 5 weeks. Peak VO(2), thigh muscle volume, and blood samples [for IGF-I, IGF-binding proteins (IGFBP)-1 to -6, and GHBP] were measured. At baseline, IGF-I was significantly correlated with both peak VO(2) (r = 0.44, P < 0.02) and muscle volume (r = 0.58, P < 0.004). IGFBP-1 was negatively correlated with muscle volume (r = -0.71, P < 0.0001), as was IGFBP-2. IGFBP-4 and -5 were significantly correlated with muscle volume. We found a threshold value of body mass index percentile (by age) of about 71, above which systematic changes in GHBP, IGFBP-1, and peak VO(2) per kilogram were noted, suggesting decreases in the following: 1) GH function, 2) insulin sensitivity, and 3) fitness. Following the training intervention, IGF-I increased in control (19.4 +/- 9.6%, P < 0.05) but not trained subjects, and both IGFBP-3 and GHBP decreased in the training group (-4.2 +/- 3.1% and -9.9 +/- 3.8%, respectively, P < 0.05). Fitness in prepubertal girls is associated with an activated GH-->IGF-I axis, but, paradoxically, early in a training program, children first pass through what appears to be a neuroendocrine state more consistent with catabolism.

We recently demonstrated that a brief endurance type training program led to increases in thigh muscle mass and peak oxygen uptake (VO(2)) in prepubertal girls. In this study, we examined the effect of training on the GH-->insulin-like growth factor I (GH-->IGF-I) axis, a system known to be involved both in the process of growth and development and in the response to exercise. Healthy girls (mean age 9.17 +/- 0.10 yr old) volunteered for the study and were randomized to control (n = 20) and training groups (n = 19) for 5 weeks. Peak VO(2), thigh muscle volume, and blood samples [for IGF-I, IGF-binding proteins (IGFBP)-1 to -6, and GHBP] were measured. At baseline, IGF-I was significantly correlated with both peak VO(2) (r = 0.44, P < 0.02) and muscle volume (r = 0.58, P < 0.004). IGFBP-1 was negatively correlated with muscle volume (r = -0.71, P < 0.0001), as was IGFBP-2. IGFBP-4 and -5 were significantly correlated with muscle volume. We found a threshold value of body mass index percentile (by age) of about 71, above which systematic changes in GHBP, IGFBP-1, and peak VO(2) per kilogram were noted, suggesting decreases in the following: 1) GH function, 2) insulin sensitivity, and 3) fitness. Following the training intervention, IGF-I increased in control (19.4 +/- 9.6%, P < 0.05) but not trained subjects, and both IGFBP-3 and GHBP decreased in the training group (-4.2 +/- 3.1% and -9.9 +/- 3.8%, respectively, P < 0.05). Fitness in prepubertal girls is associated with an activated GH-->IGF-I axis, but, paradoxically, early in a training program, children first pass through what appears to be a neuroendocrine state more consistent with catabolism.

Little is known about the relationship among training, energy expenditure, muscle volume, and fitness in prepubertal girls. Because physical activity is high in prepubertal children, we hypothesized that there would be no effect of training. Forty pre- and early pubertal (mean age 9.1 +/- 0.1 yr) nonobese girls enrolled in a 5 day/wk summer school program for 5 wk and were randomized to control (n = 20) or training groups (n = 20; 1.5 h/day, endurance-type exercise). Total energy expenditure (TEE) was measured using doubly labeled water, thigh muscle volume using magnetic resonance imaging, and peak O(2) uptake (VO(2 peak)) using cycle ergometry. TEE was significantly greater (17%, P < 0.02) in the training girls. Training increased thigh muscle volume (+4.3 +/- 0.9%, P < 0.005) and VO(2 peak) (+9.5 +/- 6%, P < 0.05), effects surprisingly similar to those observed in adolescent girls using the same protocol (Eliakim A, Barstow TJ, Brasel JA, Ajie H, Lee W-NP, Renslo R, Berman N, and Cooper DM, J Pediatr 129: 537-543, 1996). We further compared these two sample populations: thigh muscle volume per weight was much lower in adolescent compared with prepubertal girls (17.0 +/- 0.3 vs. 27.8 +/- 0.6 ml/kg body mass; P < 0.001), and allometric analysis revealed remarkably low scaling factors relating muscle volume (0.34 +/- 0.05, P < 0.0001), TEE (0.24 +/- 0. 06, P < 0.0004), and VO(2 peak) (0.28 +/- 0.07, P < 0.0001) to body mass in all subjects. Muscle and cardiorespiratory functions were quite responsive to brief training in prepubertal girls. Moreover, a retrospective, cross-sectional analysis suggests that increases in muscle mass and VO(2 peak) may be depressed in nonobese American girls as they mature.