Training, muscle volume, and energy expenditure in nonobese American girls.

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.

Postnatal thyroxine supplementation in infants less than 32 weeks' gestation: effects on pulmonary morbidity.

OBJECTIVE: Transient hypothyroxinemia in premature newborns has been linked with poor neonatal outcomes. We designed this study to evaluate the effects of early thyroxine (T4) administration in the premature infant. STUDY DESIGN: A total of 49 newborns less than 32 weeks' gestation, were randomized in a double-blind, placebo-controlled trial. Within the first 48 hours of life, T4 (10 or 20 micrograms/kg; intravenous or through nasogastric tube, respectively) was administered for a total of 21 days. Chronic lung disease, the primary outcome variable, was defined by oxygen dependency at 28 days of life. RESULTS: The incidence of chronic lung disease, death, grade III or IV intraventricular hemorrhage, periventricular leukomalacia, and sepsis was not different in the placebo and treated groups. CONCLUSION: Early T4 supplementation in preterm newborns less than 32 weeks' gestation does not decrease the incidence of chronic lung disease or other complications of prematurity.

Adiposity, lipid levels, and brief endurance training in nonobese adolescent males.

Physical activity during childhood and adolescence may influence the development of childhood obesity and cardiovascular disease later in life. Research focused prospectively on the effects of training on lipid levels in nonobese subjects, and studies using noninvasive measurements of subcutaneous and intraabdominal fat are lacking. It was hypothesized in nonobese sedentary adolescent males that a brief endurance-type exercise training intervention would reduce body fat and improve lipid profiles. Thirty-eight healthy, nonobese sedentary adolescent males (mean age 16 +/- 0.7 years old; 18 controls, 20 trained) completed a 5-week prospective, randomized, controlled study. Adiposity was measured using magnetic resonance images of the thigh and abdomen (subcutaneous abdominal adipose tissue [SAAT] and intraabdominal adipose tissue [IAAT]). Lipid measurements included serum triglycerides (TG), total cholesterol (TC), HDL and LDL cholesterol. There was no change in body weight in either control or training groups. Training led to small but significant reductions in thigh fat (-4.6 +/- 1.5%, p < 0.03) and SAAT% (1.7 +/- 0.8%, p < 0.02). There was no change in IAAT%. Unexpectedly in the control group there were significant increases in thigh fat (5.2 +/- 1.7%, p<0.01), SAAT% (1.8 +/- 0.6, p < 0.007) and IAAT% (4.5 +/- 1.1, p < 0.0007). Training-induced changes in adiposity were not accompanied by changes in circulating lipids. In nonobese adolescent males a brief period of endurance training led to reductions in body fat depots without weight change while body fat increased rapidly in the control group. Exercise training did not change lipid levels, the latter may require more sustained alterations in patterns of physical activity.

Effect of exercise training on erythrocyte insulin-like growth factor-I receptor binding in adolescent males.

Exercise training leads to tissue anabolism by acting through the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis, but the role of tissue IGF-I receptors in this process is not known. Erythrocyte IGF-I receptor binding is known to be affected by circulating levels of IGF-I. We hypothesized that training would lead to alterations in erythrocyte IGF-I binding. Thirty-eight adolescent males (mean age 16+/-0.7 yr) were randomized to a control (n=18) or endurance training intervention lasting 5 weeks. Erythrocyte IGF-I binding was measured by standard techniques. Quantity of receptor binding sites (R), binding affinity constant (Kaff), and nonspecific binding (NS) were calculated. Training led to increases (p<0.05) in 1) Kaff x R - an index of overall binding capacity (control, 7.3 +/-8.0%; trained, 60+/-21%); and 2) NS (control, 1.5+/-6.6%; trained 23.2+/-7.5%). Kaff, R, and R/erythrocyte increased in trained subjects, but not significantly so. These results suggest a training-associated upregulation of IGF-I binding. Finally, the unexpected increase in NS may reflect IGF binding protein activity, rather than changes in the erythrocyte IGF-I receptors themselves.

Mosaic tetrasomy 8q: inverted duplication of 8q23.3qter in an analphoid marker.

We observed an analphoid marker chromosome stable through cell division in a 16-year-old girl with developmental delay, short stature, limb contractures, and ovaries containing multiple cysts. She also developed myasthenia gravis at 15 years. The marker chromosome, present in 75% of metaphases (and in 90% of transformed lymphoblastoid cells), was C-band negative, and had no pan alpha-satellite sequences detectable by fluorescence in situ hybridization (FISH). The 8q origin of the marker was determined by use of subtelomeric probes and was confirmed by chromosome 8 painting probes. The marker was shown to be an inversion duplication of 8q when subtelomeric, telomeric, and c-myc FISH probes hybridized to both ends of the marker. The karyotype was 47,XX,+inv dup(8)(qter--> q23.3::q23.3-->[neocen]-->qter), resulting in tetrasomy for 8q23.3qter. The parents had normal karyotypes. Centromeric proteins CENP-C and CENP-E were present, but alpha associated centromere protein CENP-B was absent at a position defining a neocentromere.

Effect of growth hormone therapy in mitigating hypoxia-induced and food restriction-induced growth retardation in the newborn rat.

OBJECTIVE: Hypoxia may alter the neuroendocrine control of catabolic and anabolic states early in postnatal life by modulating the growth hormone-insulin-like growth factor-I (GH-IGF-I) system. We wondered: a) to what extent hypoxia effects on the GH-IGF-I axis differed from those of food deprivation alone; and b) whether administration of exogenous GH mitigates alterations of the GH-IGF-I axis caused by hypoxia or food restriction. DESIGN: Prospective laboratory investigation using nursing dams and suckling pups. Experimental groups included: a) room air control subjects; b) hypoxia-exposed subjects (FIO2, 0.12); or c) room air breathing subjects whose dam food intake was matched to that of hypoxic dams. Half of the pups in each group were administered rat GH (100 microg subcutaneously each day), and the remaining received vehicle alone. The intervention lasted 18 days. SETTING: Research laboratory in a university medical center. SUBJECTS: Twelve litters of 1-day-old Sprague-Dawley rat pups and nursing dams. INTERVENTIONS: Hypoxia exposure, food restriction, GH administration. MEASUREMENTS AND MAIN RESULTS: By the end of the study, body weights of the hypoxic and pair-fed pups were significantly lower than the weights of control animals (p < .001 for both groups), and weight gain correlated significantly with total dam food consumption (r2 = .85, p < .0001). GH administration increased weight gain only in hypoxic animals (p < .001) but it increased tail lengths significantly in both hypoxic and control pups (p < .001). Serum IGF-I levels in both hypoxic and pair-fed pups were significantly lower than in control animals. Serum IGF-binding protein-3 (IGFBP-3) was significantly lower in the hypoxic compared with the control animals. GH administration resulted in significant increases in serum levels of IGFBP-3 in both the control (p < .05) and the hypoxic (p < .01) pups compared with their vehicle-treated litter mates. CONCLUSIONS: Exogenous GH attenuates growth impairment associated with hypoxia but not with food restriction, and these effects may be mediated in part by IGFBP-3.

GH response to exercise: assessment of the pituitary refractory period, and relationship with circulating components of the GH-IGF-I axis in adolescent females.

The concept of pituitary refractory period for GH secretion has been previously described. To measure the length of this refractory period we performed an exercise provocation test for GH secretion immediately following multiple overnight GH blood sampling. In addition, we correlated the magnitude of the GH response to a single exercise input with mean overnight GH, IGF-I and circulating IGFBP levels. 23 healthy adolescent females (15-17 yr) performed 10-min constant cycle ergometry at a power normalized to each subject's aerobic and anaerobic capacity. GH was measured every 10 min starting 10 min before exercise and then for 60 min after the exercise bout. Mean nocturnal GH was calculated from overnight values obtained every 20 min over a 12-h period. Pre-exercise GHBP, IGF-I and IGFBPs 1-5 were assessed using standard techniques. In five subjects, a spontaneous GH peak had preceded the exercise test by 1 hour or less, and no response to exercise was found. In the remaining 18 subjects, a GH peak (6.8 +/- 1.3 ng/ml, p < 0.0001) was observed at 32 +/- 4 min after the onset of exercise. The GH response to exercise was not correlated with fitness, mean GH or IGF-I but was correlated with IGFBP-3 (r = 0.65, p < 0.05). Spontaneous GH pulses may acutely render the pituitary refractory to exercise stimuli. The length of this refractory period is approximately 1 hour. The data corroborate the idea that while relationships exist among the various components of the GH-IGF-I axis, no single factor identified to date fully reflects GH-IGF-I "tone".

Increased physical activity and the growth hormone-IGF-I axis in adolescent males.

Insulin-like growth factor-I (IGF-I) is associated with muscle hypertrophy, and circulating IGF-I levels are correlated with fitness. To test the hypothesis that IGF-I increases with increased physical activity in adolescent males, 38 subjects (16 +/- 0.7 yr old) were randomized to control (n = 18) or increased physical activity groups for 5 wk. Before and after the intervention, we measured thigh muscle volume using magnetic resonance imaging and serum levels of mean growth hormone (GH) by overnight multiple sampling, GH binding protein (GHBP), IGF-I, and IGFBPs 1-5 by standard assays. Energy expenditure was assessed with the doubly labeled water technique toward the end of the study. In the training subjects there was 1) a significant increase in thigh muscle volume (+3.6 +/- 1%), 2) 15.5 +/- 3.3% greater energy expenditure than in controls, and 3) no evidence of weight loss (+1.44 +/- 0.4%). In contrast to our hypothesis, but similar to our recent observations in adolescent females, training decreased IGF-I (-12 +/- 4%, P < 0. 005). Moreover, training substantially reduced GHBP (-21 +/- 4%, P < 0.00002) and increased IGFBP-2 (+40 +/- 16%, P < 0.008). Brief training increased muscle volume in weight-stable adolescent males and, surprisingly, influenced not only IGF-I but GHBP and IGFBP-2 as well in a manner typically found in energy-deficient states.

Peak oxygen uptake, muscle volume, and the growth hormone-insulin-like growth factor-I axis in adolescent males.

PURPOSE: The growth effects of exercise appear to be mediated in part by central neuroendocrine control reflected in circulating levels of growth hormone (GH), insulin-like growth factor-I (IGF-I), and their binding proteins (BP). In previous studies positive correlations between peak VO2 and circulating IGF-I have been demonstrated. The relationship between peak oxygen uptake and these potential regulating factors has not been examined in adolescent males where patterns of GH pulsatility and levels of IGF-I are rapidly changing. METHODS: Forty-three healthy adolescent males (age 16 +/- 0.7 yr, 70% at Tanner V) performed cycle ergometry to determine p oxygen uptake (peak VO2), and magnetic resonance images to determine the thigh muscle volume. Baseline blood samples were collected for GHBP, the extracellular portion of the GH tissue receptor (by ligand mediated immunofunctional assay), IGF-I (by RIA), and IGFBPs 1-5 (by RIA). Mean GH was determined from samples obtained every 20 min overnight. RESULTS: Peak VO2/kg was positively correlated with mean overnight GH levels (r = 0.41, P < 0.005). Both peak VO2/kg and thigh muscle volume/kg were negatively correlated with GHBP (r = -0.33, P < 0.02) and IGFBP-4 (r = -0.52, P < 0.005). There were no correlations between peak VO2/kg and IGF-I or IGFBPs 1-3, and 5. CONCLUSIONS: GH pulsatility is increased adolescent males who have higher peak VO2, but this did not translate into increases in IGF-I. We speculate that in the fitter males, lower GHBP levels may reduce hepatic sensitivity to GH. Thus, circulating IGF-I was unchanged despite higher mean GH in subjects with higher peak VO2. IGFBP-4 which is known to inhibit IGF-I was negatively correlated with peak VO2 leading, possibly, to increased IGF-I bioactivity. Fitness (as assessed by muscle mass and peak VO2) does modulate the GH-IGF-I axis, but not solely through circulating IGF-I; both GHBP and IGFBPs play important roles.

Erythrocyte insulin-like growth factor-L binding in younger and older males.

OBJECTIVE: Insulin-like growth factor-1 (IGF-l) levels are lower in older compared with younger subjects. We tested the hypothesis that the reduction in circulating IGF-l would be accompanied by upregulation in tissue IGF-l binding in at least some tissues. We tested erythrocyte IGF-l binding since blood is an accessible tissue in humans, and there is growing evidence to suggest that erythrocyte IGF-l binding is influenced by circulating IGF-l. DESIGN AND PATIENTS: We compared 9 healthy older males (61-68 years old) with 9 healthy younger males (15-19 years old). MEASUREMENTS: Standard techniques were used to assay circulating IGF-l and IGF binding proteins 1-5 (IGFBPs 1-5). Erythrocyte IGF-l binding was first measured by studies in which native [125l]-IGF-l was displaced with unlabelled native IGF-l. In order to determine a possible role for IGF binding proteins (IGFBP), native [125l]-IGF-l was displaced with des-(1-3)IGF-1, which binds with IGF receptors but not IGFBPs. RESULTS: As expected, circulating IGF-l was significantly lower in the older compared with the younger subjects. In addition, IGFBP-3 and 5 were significantly lower, and IGFBP-4 higher, in older compared with younger subjects. When native [125l]-IGF-l was displaced with unlabelled native IGF-l, the number of IGF-l binding sites per erythrocyte was higher in the older subjects (43 +/- 5 vs. 18 +/- 2, older vs. younger, respectively; P < 0.05). In contrast, when native [125l]-IGF-l was displaced with des-(1-3), IGF-l binding capacity was not different between the two age groups. CONCLUSIONS: Erythrocyte IGF binding was increased in older compared with younger subjects. Surprisingly, the mechanism of the increase may not be a simple up regulation of IGF-l receptors in response to reduced circulating IGF-l, but possibly by an increase in the levels of as yet unidentified erythrocyte membrane-associated IGF binding proteins.

Fitness and the effect of exercise training on the dietary intake of healthy adolescents.

OBJECTIVE: In healthy, nonobese, adolescent males and females to: (1) Determine the relationship between fitness and energy intake; (2) assess the effect of five-weeks endurance training on energy intake and food choice and (3) compare food record assessments of energy intake with doubly-labeled water (DLW) measurement of total energy expenditure (TEE). DESIGN: (1) Cross sectional analysis of fitness and food intake and (2) Prospective, randomized, controlled interventional study of endurance-type exercise training in 44 females and 44 males (age range, 15-17 y). MEASUREMENTS: Pre and end interventional three day food records were successfully collected from 32 females (15 controls, 17 trained) and 39 males (19 controls, 20 trained). Fitness was assessed from cycle ergometry as peak oxygen uptake normalized both to thigh muscle mass and body weight. Thigh muscle mass was measured by magnetic resonance imaging. TEE using the DLW technique was measured in 12 females (6 controls, 6 trained) and 20 males (10 controls, 10 trained) during weeks 4-5 of the exercise training program (simultaneously with the second assessment of food records). Food record data were analyzed using the Minnesota Nutrition Data System. RESULTS: Fitness was correlated with self reported total caloric intake in males but not females. In females, there was a significant increase in fat intake (19.8+/-9%, P < 0.05) and a significant decrease in carbohydrate intake (-9.8+/-4%) in the trained subjects. No changes were observed in the control subjects. Energy expenditure (2072+/-52 kcal/d) was significantly greater than the estimated energy intake (1520+/-112 kcal/d, P < 0.007) during the intervention in the trained, but not control, subjects. However, there was no weight change in either control or trained subjects. In males, no changes were observed in food choice in either control or trained subjects. Similar to the females, energy expenditure (2425+/-22 kcal/d) was significantly greater than the estimated energy intake (2168+/-117 kcal/d, P < 0.05) during the intervention in the trained, but not control, subjects. No weight changes were observed in either group. CONCLUSIONS: Fitness is associated with increased self-reported energy intake in males but not females, while exercise training led to alterations in food selection (greater fat and reduced carbohydrate) only in females. These observations could reflect specific gender differences, or, alternatively, the generally lower levels of fitness in the females. The apparent negative energy balance without evidence for weight loss in both the trained males and females suggests a systematic under reporting of food intake during exercise programs in adolescents, and indicates the possibility that errors in self reported food intake might be greater during transitions from one level of energy expenditure to another.

Growth hormone therapy of Turner's syndrome: beneficial effect on adult height.

OBJECTIVE: To carry out a multicenter, prospective, randomized trial of human growth hormone (GH), alone or in combination with oxandrolone (OX), in patients with Turner's syndrome (TS). METHODS: In an initial phase lasting 12 to 24 months, 70 girls with TS, verified by karyotype, were randomly assigned to one of four groups: (1) observation, (2) OX, (3) GH, or (4) GH plus OX. After completion of the first phase, group 3 subjects continued to receive GH only. All other subjects were treated with GH plus OX. Subjects were followed up until attainment of adult height and/or cessation of treatment. Data from this trial were compared with growth characteristics of 25 American historical subjects with TS (matched for age, height, parental target height, and karyotype) who never received either GH or androgens. RESULTS: Of the 70 subjects enrolled, 60 completed the clinical trial. The 17 subjects receiving GH alone all completed the trial and reached a height of 150.4+/-5.5 cm (mean +/- SD), 8.4+/-4.5 cm taller than their mean projected adult height at enrollment (95% confidence interval [CI]: 6.3 to 10.6 cm). The 43 subjects receiving GH plus OX attained a mean height of 152.1+/-5.9 cm, 10.3+/-4.7 cm taller than their mean projected adult height (95% CI: 8.9 to 11.7 cm). The historical control subjects had a mean adult height of 144.2+/-6.0 cm, precisely matching their original projected adult height of 144.2+/-6.1 cm. CONCLUSIONS: GH, either alone or in combination with OX, is capable of stimulating short-term growth and augmenting adult height in girls with TS. With early diagnosis and initiation of treatment, an adult height of more than 150 cm is a reasonable goal for most girls with TS.

Increase in muscle IGF-I protein but not IGF-I mRNA after 5 days of endurance training in young rats.

Five days of treadmill training in rats leads to increased muscle size and running time. This was used to examine the effect of exercise on circulating insulin-like growth factor I [IGF-I; radioimmunoassay (RIA)], local muscle (hindlimb) IGF-I (by RIA), and muscle IGF-I mRNA (by ribonuclease protection assay). Eight-week-old female Sprague-Dawley rats were divided into three groups: control (n = 10); single-exercise test (n = 10), untrained but with one maximal exercise test at the end of the study; and training (n = 16), trained for 5 days and one maximal exercise test on day 6. There were no differences among the groups with respect to circulating IGF-I. Muscle IGF-I protein in trained rats (4.2 +/- 1.5 ng/g of muscle tissue) was significantly greater than both control (0.27 +/- 0.1 ng/g) and single-exercise test (0.62 +/- 0.19 ng/g, P < 0.05 by analysis of variance). There was no difference among the groups in IGF-I mRNA gene expression. These data suggest that there is an early, marked, local muscle increase in IGF-I protein in response to exercise. This increase, however, may not be related to increased muscle IGF-I gene expression. Moreover, the IGF-I response was probably local in nature since it was not matched by any increase in circulating IGF-I.

Evidence for increased bone formation following a brief endurance-type training intervention in adolescent males.

The effect of exercise training, particularly relatively brief periods, on bone turnover markers in adolescents has been poorly studied. Thirty-eight healthy males (16+/-0.7 years) participated in a 5-week summer school program in which 20 subjects were randomly assigned to a training group consisting of 2 h/day, 5 days/week of endurance exercise, and 18 subjects were assigned to a control group. Bone formation was assessed by measurements of circulating osteocalcin, bone-specific alkaline phosphatase (BSAP), and the C-terminal procollagen peptide (PICP). Bone resorption was assessed by urinary levels of free deoxypyridinoline cross-links (dPYR) and the C-(CTX) and N-terminal (NTX) telopeptide cross-links. Prior to training, there was a weak positive correlation between fitness and PICP (r = 0.27, p < 0.05), but no correlations were observed between fitness and either the other markers of bone formation or bone resorption. Training led to a significant increase in (1) osteocalcin (15+/-4%, p < 0.03), (2) BSAP (21+/-6%, p < 0.02), and (3) PICP (30+/-11%, p < 0.03) and to a significant decrease in NTX (-21 +/- 3%, p < 0.05). These bone turnover markers did not change in the control subjects (osteocalcin, 0+/-4%; BSAP, 2+/-4%; PICP, -4 +/- 6%; NTX, -6 +/- 4%). There was no change in urinary dPYR and CTX in either control or trained subjects. Fitness is only weakly, if at all, correlated with bone formation, but a relatively brief period of endurance training leads to a substantial increase in bone formation markers in adolescent males. School-based, short-term exercise training programs could play a role in enhancing bone formation in adolescents.

Exercise-induced changes in circulating growth factors with cyclic variation in plasma estradiol in women.

The effect of 10 min of high-intensity cycling exercise on circulating growth hormone (GH), insulin-like growth factors I and II (IGF-I and -II), and insulin-like growth factor binding protein 3 (IGF BP-3) was studied in nine eumenorrheic women (age 19-48 yr) at two different phases of the menstrual cycle. Tests were performed on separate mornings corresponding to the follicular phase and to the periovulatory phase of the menstrual cycle, during which plasma levels of endogenous estradiol (E2) were relatively low (272 +/- 59 pmol/l) and high (1,112 +/- 407 pmol/l), respectively. GH increased significantly in response to exercise under both E2 conditions. Plasma GH before exercise (2.73 +/- 2.48 vs. 1.71 +/- 2.09 micrograms/l) and total GH over 10 min of exercise and 1-h recovery (324 +/- 199 vs. 197 +/- 163 ng) were both significantly greater for periovulatory phase than for follicular phase studies. IGF-I, but not IGF-II, increased acutely after exercise. IGF BP-3, assayed by radioimmunoassay, was not significantly different at preexercise, and exercise, or at 30-min recovery time points and was not different between the two study days. When assayed by Western blot, however, there was a significant increase in IGF BP-3 30 min after exercise for the periovulatory study. These findings indicate that the modulation of GH secretion associated with menstrual cycle variations in circulating E2 affects GH measured after exercise, at least in part, by an increase in baseline levels. The acute increase in IGF-I induced by exercise appears to be independent of the GH response and is not affected by menstrual cycle timing.

Physical fitness, endurance training, and the growth hormone-insulin-like growth factor I system in adolescent females.

We examined the relationship between physical fitness and circulating components of the GH-insulin-like growth factor I (IGF-I) system [i.e. GH, GH-binding protein (GHBP), IGF-I, and IGF-binding proteins 1-5 (IGFBP-1 through-5)] in adolescent females (age range, 15-17 yr). The study consisted of 1) a cross-sectional protocol (n = 23) in which GH-IGF-I components were correlated with fitness, as estimated by thigh muscle volume and maximal O2 uptake; and 2) a prospective study in which fitness, GH-IGF-I system components, and osteocalcin were examined before and after a 5-week period of endurance-type training (control, n = 6; trained, n = 10). The cross-sectional analysis revealed significant (P < 0.05) positive correlations between fitness and 1) mean 12-h overnight GH levels, 2) GHBP, and 3) IGF-I. Muscle volume was negatively correlated with both IGFBP-2 and -4. The prospective training study was associated with 1) increases in circulating osteocalcin (39 +/- 14%; P < 0.007), and 2) decreases in IGF-I (-14 +/- 5%; P < 0.05) and IGFBP-5 (-10 +/- 4%; P < 0.04). Unexpectedly, IGFBP-3 fell in both control (-8 +/- 2%; P < 0.01) and trained subjects (-5 +/- 3%; P < 0.05), and GHBP was reduced only among control subjects (-10 +/- 7%; P < 0.04). In summary, fitter adolescent girls tended to have increased mean serum GH, GHBP, and IGF-I. In contrast, brief endurance training led to increases in muscle mass and serum osteocalcin that were not accompanied by increases in GH or IGF-I. In fact, training may, in the short term, have led to a catabolic state hormonally expressed by reductions in IGF-I and IGFBP-5.

Effect of exercise training on energy expenditure, muscle volume, and maximal oxygen uptake in female adolescents.

OBJECTIVES: American female adolescents are at high risk of a physically inactive lifestyle that likely leads to health problems later in life. We hypothesized that a brief program of endurance exercise training in female adolescents would result in increased energy expenditure and quantifiable structural and functional adaptations. STUDY DESIGN: Forty-four high school girls (aged 15 to 17 years, none were elite athletes) enrolled in a 5-day per week anatomy class for 5 weeks and were randomly assigned to control (n = 22) and training groups. All subjects participated in a 2-hour daily teaching program. During the remaining time (2 hours), the training group members underwent endurance-type training and control group subjects participated in a computer workshop. The intervention was assessed by (1) comparison of total energy expenditure between groups with the doubly labeled water technique, (2) determination of changes in thigh muscle volume by magnetic resonance imaging, and (3) determination of changes in maximal oxygen uptake by use of respiratory gas exchange responses. RESULTS: Total energy expenditure was significantly greater (15.3%) in the training group compared with the control subjects (p < 0.003). Five weeks of training led to a 4.3% +/- 1% increase in thigh muscle volume (p < 0.0002) and a 12.1% +/- 3.7% increase in maximal oxygen uptake (p < 0.004); there were no changes in the control group. The training effect was most pronounced in the least fit subjects. CONCLUSIONS: Exercise training programs for female adolescents can be successfully integrated into a high school summer curriculum. Quantifiable, substantial structural and functional responses occur with relatively short periods of training. Approximately 60% of the training response was related to factors independent of muscle size per se. These data may serve to better design physical activity programs for female adolescents.

Acute effect of brief low- and high-intensity exercise on circulating insulin-like growth factor (IGF) I, II, and IGF-binding protein-3 and its proteolysis in young healthy men.

We measured circulating levels of the GH insulin-like growth factor (IGF) system in response to brief exercise of different intensities. Ten males (mean age 28 +/- 5 yr) were studied on three separate occasions: once under resting conditions (control) and once each performing 10 min of low- or high-intensity exercise. Blood samples were assayed by RIA for GH, IGF-I and -II, IGF-binding protein-3 (IGFBP-3), and IGFBP-3 proteolytic activity. After 10 min of low-intensity exercise, IGF-I and IGFBP-3 had increased over preexercise baseline by 7.7 +/- 2.7% (P < 0.05) and 12.5 +/- 3.3% (P < 0.004), respectively. After 10 min of high-intensity exercise, all measured components of the IGF system were increased: IGF-I by 13.3 +/- 3.2% (P < 0.002), IGF-II by 15.7 +/- 3.1 (P < 0.01), and IGFBP-3 by 23 +/- 6% (P < 0.001). IGFBP-3 proteolytic activity also was increased (44 +/- 14% above baseline, P < 0.05). GH reached its peak 10 min after the cessation of high-intensity exercise, unlike the earlier peaks of IGF-I and II. In summary: 1) brief exercise leads to small but significant increases in circulating IGF-I, IGF-II, IGFBP-3, and IGFBP-3 proteolysis; and 2) these responses may be influenced by exercise intensity. The IGF responses seem to be unrelated to GH. Acute exercise-induced proteolysis of IGFBP-3 may contribute to anabolic effects of physical activity by increasing the bioavailability of IGF-I.

Microdontia with severe microcephaly and short stature in two brothers: osteodysplastic primordial dwarfism with dental findings.

Two brothers from a black family had microcephaly, short stature, and generalized microdontia. Endocrine and chromosome studies were normal, and mild skeletal manifestations were present. The patients may represent a distinct dental-skeletal dysplasia, possibly osteodysplastic primordial dwarfism type II. Attention to dental manifestations in similar cases may be useful for classification.

Failure of anabolism in malnourished cancer patients receiving growth hormone: a clinical research center study.

Previous work demonstrated that the provision of adequate or even excessive nutritional support is unable to reverse the negative nitrogen balance in many cancer patients. Our goal in a preliminary, short term study was to determine whether three daily GH injections (0.125 mg/kg.day, im) in cancer patients would increase insulin-like growth factor I concentrations and reverse the catabolic metabolic response to cancer, as indicated by reduced urinary nitrogen loss. Three days of GH therapy were associated with a significant increase in mean circulating GH (1.6 +/- 0.4 vs. 15.4 +/- 3.0 micrograms/L; P < 0.01), insulin-like growth factor I (112 +/- 15 vs. 329 +/- 54 micrograms/L; P < 0.01), insulin (57 +/- 11 vs. 184 +/- 46 pmol/L; P < 0.01), glucagon (63 +/- 11 vs. 77 +/- 11 ng/L; P < 0.05), and glucose (5.4 +/- 0.1 vs. 6.2 +/- 0.2 mmol/L; P < 0.05) concentrations. Twenty-four-hour urinary urea nitrogen (6.7 +/- 0.9 vs. 4.9 +/- 0.5 g; P < 0.05) and total nitrogen (7.8 +/- 1.2 vs. 6.0 +/- 1.2 g; P < 0.05) were significantly reduced. GH treatment in the group overall failed to alter leucine appearance (77.3 +/- 4.0 vs. 76.1 +/- 5.4 mumol/kg.h), leucine oxidation (11.8 +/- 1.5 vs. 9.6 +/- 1.0 mumol/kg.h), hepatic glucose production (13.5 +/- 0.8 vs. 14.2 +/- 0.8 mumol/kg.min), or estimated mean nitrogen balance (-0.24 +/- 0.97 vs. 0.85 +/- 0.75 g/day; t = 1.56; P = 0.10). Nitrogen balance was directly correlated with the percentage of the patient's ideal body weight (r = 0.776; P < 0.01). Seven of the 10 cancer patients were at or above 90% of ideal body weight, and they had a significant improvement in nitrogen balance (-1.46 +/- 0.99 vs. 0.60 +/- 1.03 g/day; P < 0.01). These patients also demonstrated a significant reduction in leucine oxidation (14.1 +/- 1.3 vs. 10.0 +/- 1.4 mumol/kg.h) and leucine appearance (81.2 +/- 3.8 vs. 72.9 +/- 3.3 mumol/kg.h; P < 0.05). This suggests that those most severely malnourished cancer patients may not respond anabolically to short term GH administration. We conclude that GH administration may be anabolic in cancer patients if there is not severe preexisting malnutrition.