Acceleration Of Linear Growth Research Articles

Altered IGF-I activity and accelerated bone elongation in growth plates precede excess weight gain in a mouse model of juvenile obesity.

Nearly one-third of children in the United States are overweight or obese by their preteens. Tall stature and accelerated bone elongation are characteristic features of childhood obesity, which cooccur with conditions such as limb bowing, slipped epiphyses, and fractures. Children with obesity paradoxically have normal circulating IGF-I, the major growth-stimulating hormone. Here, we describe and validate a mouse model of excess dietary fat to examine mechanisms of growth acceleration in obesity. We used in vivo multiphoton imaging and immunostaining to test the hypothesis that high-fat diet increases IGF-I activity and alters growth plate structure before the onset of obesity. We tracked bone and body growth in male and female C57BL/6 mice (n = 114) on high-fat (60% kcal fat) or control (10% kcal fat) diets from weaning (3 wk) to skeletal maturity (12 wk). Tibial and tail elongation rates increased after brief (1-2 wk) high-fat diet exposure without altering serum IGF-I. Femoral bone density and growth plate size were increased, but growth plates were disorganized in not-yet-obese high-fat diet mice. Multiphoton imaging revealed more IGF-I in the vasculature surrounding growth plates of high-fat diet mice and increased uptake when vascular levels peaked. High-fat diet growth plates had more activated IGF-I receptors and fewer inhibitory binding proteins, suggesting increased IGF-I bioavailability in growth plates. These results, which parallel pediatric growth patterns, highlight the fundamental role of diet in the earliest stages of developing obesity-related skeletal complications and validate the utility of the model for future studies aimed at determining mechanisms of diet-enhanced bone lengthening.NEW & NOTEWORTHY This paper validates a mouse model of linear growth acceleration in juvenile obesity. We demonstrate that high-fat diet induces rapid increases in bone elongation rate that precede excess weight gain and parallel pediatric growth. By imaging IGF-I delivery to growth plates in vivo, we reveal novel diet-induced changes in IGF-I uptake and activity. These results are important for understanding the sequelae of musculoskeletal complications that accompany advanced bone age and obesity in children.

Особенности линейного роста школьников с различным уровнем физического развития

Objective. Determine the options for pubertal spurt in children with different levels of physical development in pre-pubertal age. Patients and methods. The analysis of the annual increase in body length and weight indicators in 645 schoolchildren (331 boys and 314 girls) aged 8 to 16 years was carried out. Depending on the compliance of the child's body length indicator with the WHO Growth Reference 2007 standards at the age of 8, schoolchildren are divided into groups: with average physical development; with physical development above average; with physical development below average. Results. The dynamics of the increase in body length and weight during the pubertal growth spurt has differences in children with different levels of physical development. Acceleration of linear growth in boys with average physical development is of a prolonged and low-amplitude type. The pubertal growth spurt in children with physical development above average is more pronounced in amplitude and limited in time; with physical development below average – has a more pronounced amplitude and lasts a shorter time than peers with average physical development. In girls with all types of physical development, the pubertal leap in linear growth is insignificantly expressed and prolonged in time, especially in schoolgirls with average and above average physical development. Conclusion. The data can be useful as a guide in predicting the course of pubertal spurt in children in the practice of clinical examination of the child population, in determining adequate physical activity in physical education lessons at school and in sports clubs. Key words: puberty growth spurt, children, physical development

Effect of iron and zinc supplementation on linear growth of stunted Egyptian children under 5 years of age.

Background: Linear growth is the best indicator of children’s well-being and provides an accurate marker of inequalities in human development. Aim: Study and compare the effect of micronutrients supplementation (Iron and zinc) on linear growth of infants and children less than 5 years of age suffering from stunted growth. Patients and Methods: A randomized study included 60 children less than 5 years of age came to the department of clinical nutrition in a university hospital for nutritional assessment. Cases randomly divided equally into two groups. Group A received iron supplementation only and group B received supplementation with iron and zinc. Follow up of length/height was done after 6 months of supplementation. Outcome Measures: Length/height for age and sex (birth to 5 years Z-scores, WHO, 2003). Results: On comparing the length/ height of the two groups before (p=0.472) and after supplementation (p=0.923) respectively, no statistically significant differences were found between supplementation with iron only and with iron plus zinc. Yet, upon calculation the rate of change in linear growth after 6 months, a significant difference (p=0.002) was evident on comparing group B who received zinc plus iron (mean=13.6 cm increase in height) vs. Group A who only received iron (mean=10.8 cm increase in height). Conclusion: Zinc supplementation in addition to iron led to significant acceleration of linear growth of stunted children compared to supplementation with iron alone.

Peculiarities of changes in parameters of component body composition of representatives of the youth age period detected by the method of bioimpedance analysis

The results of the study of body composition parameters using bioimpedance analysis of representatives of the youth age period of 14–19 years are presented. It is determined that the intracellular mass of biological objects, related to the total volume of liquid in it, increases with age of the object. It has been suggested that the amount of intracellular liquid relative to the total liquid in this age group increases due to an increase in the number of cells (since tissue growth occurs due to active cell division), as well as due to a decrease in the number of extracellular liquid, most often caused by an increase in adipose tissue. This pattern is observed for female and male contingent of the studied. The distributions of relative intracellular liquid depend significantly on the age and vary from approximately uniform to normal. The specific basal metabolism for males between the ages of 14 and 19 is increasing, which is explained by the increasing secretion in this category of the studied hormones of the anterior pituitary – somatotropic hormone or growth hormone. It is in puberty, especially in males causes a pronounced acceleration of linear growth and, as a consequence, an increase in the specific basal metabolism.

Mechanisms of Linear Growth Acceleration in Childhood Obesity

The obesity epidemic is alarming. Nearly one‐third of children in the Unites States are overweight or obese by the time they reach their pre‐teen years. Tall stature and accelerated bone elongation are distinctive clinical features of childhood obesity, which tend to co‐occur with painful conditions such as limb bowing, slipped epiphyses, fractures, and early onset osteoarthritis. Although linear growth rate is markedly increased, obese children paradoxically have normal circulating levels of IGF‐I, the major growth‐stimulating hormone. The causes of obesity‐induced growth acceleration remain elusive. Our lab has used a well‐established mouse model of excess dietary fat in order to examine bone elongation changes that occur with the development of juvenile obesity in young growing mice. We found, surprisingly, that brief exposure to a high‐fat diet accelerates bone elongation rate without increasing body mass or circulating IGF‐I levels. Interestingly, when we used in vivo multiphoton microscopy to measure how much systemic IGF‐I localized to growth plates in real time, we found significantly more (nearly twice as much) IGF‐I in the vasculature surrounding the growth plates of mice on a high‐fat diet relative to controls. Post‐mortem immunostaining confirmed that a high‐fat diet increased the number of activated IGF‐I receptors in the growth plate, but not total receptor number. Together, these results suggest that a high‐fat diet increases local bioavailability of IGF‐I in growth plate cartilage without altering systemic IGF‐I levels, and before changes in body mass become evident. This unique method of imaging growth factor transport in cartilage is an important advancement for addressing why linear growth is accelerated in obese children who have normal levels of systemic growth‐promoting hormones. While diets high in fat are well‐recognized for cardiovascular and metabolic complications, the role of dietary fat in bone lengthening is a novel and timely area of research. These studies may provide essential data for testing whether impeding IGF‐I actions in growth plates could be a beneficial approach for mitigating some of the deleterious skeletal consequences of childhood obesity.Support or Funding InformationSupported by the National Institute of General Medical Sciences (1P20GM121299‐01) and National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (1R15AR067451‐01).

Enhanced IGF‐I Delivery to the Growth Plate and Accelerated Bone Elongation in a Mouse Model of Juvenile Obesity

Childhood obesity can be devastating to the skeleton because its effects are often silent and undiagnosed until a child presents with disabling pain. Obese children have accelerated linear growth and skeletal maturation with diminished bone quality, leading to painful conditions such as limb bowing, joint instability, fractures, and early onset osteoarthritis. The major treatment obstacle is lack of knowledge of the underlying cause of obesity‐induced growth acceleration. Paradoxically, obese children have normal circulating levels of IGF‐I, the major growth‐stimulating hormone. Our goal was to characterize bone elongation rate and local IGF‐I delivery using a high‐fat diet to model the development of juvenile obesity in mice. We tested the hypothesis that a high‐fat diet would increase IGF‐I delivery to growth plates and bone elongation rate before the overt onset of obesity. To test this, we used in vivo multiphoton microscopy to quantify IGF‐I transport and measured bone elongation rate in weanling mice given a high‐fat diet.MethodsFemale 3‐week old C57BL/6 mice (N=26 total) were fed semi‐purified control (10% kcal fat) or high‐fat (60% kcal fat) diets for 14 days. Body mass, tail length and food intake were recorded (N=8/group). Bone elongation rate was measured from live x‐rays and fluorochrome labeled (oxytetracycline, 7.5 mg/kg IP) tibial slab sections. Femoral length was measured from digitized bone images at the 5‐week endpoint. For in vivo imaging (N=5/group), fluorescently‐labeled IGF‐I (~6 μg/g body wt) was quantified in warmed (34–36C) proximal tibial growth plates and vasculature by multiphoton microscopy at standardized depths and times as we have previously detailed. Statistical analyses were performed in SPSS using t‐tests. Significance was accepted at α = 0.05 (one‐tailed).ResultsMice on a high‐fat diet ate less than controls (2.7 vs 3.3 g/day; t = 6.3, p < 0.001), but their caloric intake was greater (13.9 vs 12.6 kcal/day; t = 2.8, p < 0.01). There were no significant differences in body mass at the start or end of the experiments; however, mice on a high‐fat diet were slightly larger and we qualitatively noted that they had more body fat. Femora (t = 4.6, p < 0.001) and tails (t = 2.9, p < 0.01) were 3% and 14% longer, respectively, in the high‐fat diet group and tibial elongation rate was over 16% greater (t = 4.1, p = 0.001). Multiphoton imaging revealed over twice as much IGF‐I in the vasculature surrounding the proximal tibial growth plates of mice on a high‐fat diet relative to chow‐fed controls (13% kcal fat), which were previously collected (t = 4.1, p < 0.01).DiscussionThese results support the hypothesis that a high‐fat diet increases bone elongation rate and IGF‐I delivery to the growth plate before the overt onset of obesity. This model is important for understanding the role of local IGF‐I transport in obesity‐induced linear growth acceleration, particularly because we show that bone length is increased without a significant change in body mass.Support or Funding InformationSupported by NIH National Institute of General Medical Sciences (1P20GM121299‐01) and National Institute of Arthritis and Musculoskeletal and Skin Diseases (1R15AR067451‐01).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effects of postweaning calorie restriction on accelerated growth and adiponectin in nutritionally programmed microswine offspring.

Poor prenatal development, followed by rapid childhood growth, conveys greater cardiometabolic risk in later life. Microswine offspring exposed to perinatal maternal protein restriction [MPR; "low protein offspring" (LPO)] grow poorly in late-fetal/neonatal stages. After weaning to an ad libitum (AL) diet, LPO-AL exhibit accelerated growth and fat deposition rates with low adiponectin mRNA, despite low-normal body fat and small intra-abdominal adipocytes. We examined effects of caloric restriction (CR) on growth and metabolic status in LPO and normal protein offspring (NPO) randomized to AL or CR diets from weaning. CR transiently reduced growth in both LPO and NPO, delaying recovery in female LPO-CR. Over 7.5-12.5 weeks, linear growth rates in LPO-CR were slower than LPO-AL ( P < 0.001) but exceeded NPO-AL; body weight growth rates fell but were lower in LPO-CR versus NPO-CR. Linear acceleration ceased after 12 weeks. At 16 weeks, percent catch-up in LPO-CR was reduced versus LPO-AL ( P < 0.001). Plasma growth hormone was low in LPO ( P < 0.02). CR normalized fat deposition rate, yet adiponectin mRNA remained low in LPO-CR ( P < 0.001); plasma adiponectin was low in all LPO-AL and in female LPO-CR. Insulin sensitivity improved during CR. We conclude that in LPO: 1) CR delays onset of, but does not abolish, accelerated linear growth, despite low growth hormone; 2) CR yields stunting via delayed onset, plus a finite window for linear growth acceleration; 3) MPR lowers adiponectin mRNA independently of growth, adiposity, or adipocyte size; and 4) MPR reduces circulating adiponectin in LPO-AL and female LPO-CR, potentially enhancing cardiometabolic risk.

The TALLYHO Mouse as a Model of Obesity‐Induced Linear Growth Acceleration

INTRODUCTIONObesity affects over 30% of adults in the United States and contributes to development of painful conditions such limb bowing, joint instability, increased risk of fractures, and early onset osteoarthritis. Nearly one third of American children are now classified as overweight or obese and are at risk of developing musculoskeletal complications because of stress from excess weight on their growing skeleton. Obese children have higher rates of linear growth and accelerated skeletal maturation when compared to their non‐obese peers. They tend to reach maturity earlier and thus typically attain normal adult height, but with diminished bone quality. It is unclear why obese children exhibit increased growth velocity. Among the animal models used in obesity research, the TALLYHO/Jng (TH) mouse is an inbred polygenic model that exhibits moderate obesity by 4‐weeks age and many of the traits consistent with human type 2 diabetes. While the physiology and genomics of the TH strain are well documented, little is known about its skeletal phenotype.OBJECTIVEThe goal of this project was to characterize skeletal growth rate of the TH mouse as a model of obesity‐induced linear growth acceleration. We tested the HYPOTHESIS that TH mice have increased bone lengths when compared to non‐obese controls on both high‐fat and standard chow diets.METHODSWe measured body mass and bone elongation rate in juvenile female TH obese and C57BL/6 (B6) non‐obese mice on standard chow during the active growth period between 3‐and 5‐weeks after birth (N=5 per group). Body mass was recorded daily and tibial elongation rate was measured using fluorochrome labeling. Femoral and humeral lengths were measured from digitized images at the study endpoint. To assess the impact of diet, we examined adult bone lengths in 20‐week‐old TH and B6 mice that were fed high‐fat (58% kcal from fat) or standard chow (13% kcal from fat) diets beginning at 4‐weeks age (N=8–10 per group).RESULTSAt 3‐weeks, TH mice on chow were over 25% larger than B6 mice and grew at an accelerated rate. By 5‐weeks, TH mice were over 31% larger and tibial elongation rates were nearly 9% greater. Tail and femoral lengths were increased by 8% and 3%, respectively, in TH mice at the 5‐week endpoint (p&lt;0.05 by independent samples t‐test). Humeral length was 2% greater, but the difference at 5‐weeks was not significant. After 16 weeks on a high‐fat diet, TH mice were twice as large in body mass than TH standard chow controls, while B6 mice on a high‐fat diet were over 20% larger than their respective controls. Femoral and humeral lengths were approximately 2% longer in the high‐fat diet groups than the chow controls within each genotype (p&lt;0.05 by one‐way ANOVA), but femoral length did not differ between genotypes at 20‐weeks age.CONCLUSIONThese data demonstrate that the TH mouse is a good model of obesity‐induced linear growth acceleration. Results from the adult study are consistent with the early maturation and attainment of normal adult height typical of obese children. Future studies utilizing the TH mouse will be important for determining mechanisms underlying obesity‐enhanced bone elongation and for potentially preventing devastating skeletal consequences of obesity.Support or Funding InformationSupported by pilot funding from the Appalachian Clinical and Translational Science Institute at the Marshall University Joan C. Edwards School of Medicine

Effect of Protein Intake from 6 to 24 Months on Insulin-Like Growth Factor 1 (IGF-1) Levels, Body Composition, Linear Growth Velocity, and Linear Growth Acceleration: What are the Implications for Stunting and Wasting?

Effect of Protein Intake from 6 to 24 Months on Insulin-Like Growth Factor 1 (IGF-1) Levels, Body Composition, Linear Growth Velocity, and Linear Growth Acceleration: What are the Implications for Stunting and Wasting?

Effect of growth hormone therapy on Taiwanese children with growth hormone deficiency

Human growth hormone (GH) has been successfully used in children with GH deficiency (GHD). However, there are few published data on the effect of GH in Taiwanese children with GHD. We performed a retrospective cohort study to identify factors influencing the effect of GH therapy on ethnic Chinese children with GHD in Taiwan. Idiopathic GHD can be classified into isolated GHD (IGHD) and multiple pituitary hormone deficiency (MPHD). The study looked at the effect of GH on the auxological, biochemical, and imaging parameters of 51 patients (13 girls and 38 boys) in three different diagnostic groups: MPHD (n = 12), IGHD (n = 8), and transient GHD (TGHD; n = 31). TGHD is defined as a GH peak >10 μg/L in re-evaluation by two GH stimulation tests approximately 6 months after discontinuation of GH therapy. The height velocity for first-year GH therapy was 7.61 ± 1.46, 8.14 ± 1.92, and 9.99 ± 2.75 cm/y in the TGHD, IGHD, and MPHD groups, respectively. After post hoc comparison, the MPHD group had a significantly accelerated height velocity in the first year compared to the TGHD group. Correlation analysis showed that a change in height standard deviation score (SDS) in the first year had a significant negative correlation with the following variables: peak GH (r = -0.52, p < 0.001), pretreatment height SDS (r = -0.49, p < 0.001), and height-target height (Ht-TH) SDS (r = -0.49, p < 0.001). Change in height SDS in the first 2 years had a significantly negative correlation with peak GH (r = -0.51, p < 0.001), insulin-like growth factor-1 SDS (r = -0.35, p = 0.022), height SDS (r = -0.60, p < 0.001), difference between bone age and chronological age (r = -0.46, p = 0.001), and Ht-TH SDS (r = -0.50, p = 0.001). After using multiple linear regression, the pretreatment GH peak value was found to be significantly associated with height increments after 1 year of GH treatment (B = -0.07, p = 0.014). The administration of GH to children with GHD results in a pronounced acceleration in linear growth during the first year of treatment, especially in those with MPHD. The diagnosis of GHD requires comprehensive auxological, biochemical, and brain magnetic resonance imaging assessment. We also suggest that patients with GHD, specifically IGHD, must undergo a re-evaluation of GH secretion after completion of GH therapy.

Accelerated growth without prepubertal obesity in nutritionally programmed microswine offspring.

Poor fetal growth and associated prepubertal growth acceleration are linked to increased risk of cardiometabolic dysfunction in later life, but whether obesity is integral to 'catch-up' growth and its ensuing risks are unknown. In microswine offspring exposed to perinatal maternal protein restriction (MPR), we measured body and organ sizes (during MPR); linear growth and weight gain (birth to 5 months of age); feed intake and utilization efficiency (5-14 weeks); and body composition at 6 and 11 weeks of age (by dual-energy X-ray absorptiometry, DEXA). During MPR, low protein offspring (LPO) showed asymmetric growth restriction with reduced body weight (Wt):length (Lth) at birth and elevated heart Wt:liver Wt ratio by 2 weeks of age. In LPO, after slow early postnatal growth (0-5 weeks), subsequent linear growth on ad libitum normal feed was absolutely accelerated (cm/week; P < 0.001) over 6-11 weeks but normal thereafter, whereas absolute weight gain (kg/week) was similar to controls but accelerated relative to lower LPO nadir weights. Concurrently, rates of fat and lean tissue accrual in LPO over 6-11 weeks were similar to normal protein offspring in absolute terms (g/5 weeks) but increased relative to lower mass at 6 weeks, yielding normal lean:Lth but reduced fat:Lth ratios at 11 weeks. LPO had higher relative feed intake (g/kg/meal) in both sexes and higher feed efficiency in females over 5-11 weeks of age. Findings suggest that postnatal linear growth acceleration preserved thinness in juvenile LPO. Given separately reported abnormalities of vascular (Bagby et al., 2011) and adipocyte function in juvenile LPO, (DuPriest et al., 2011) findings demonstrate that perinatal MPR programs catch-up growth and cardiovascular abnormalities independently of obesity.

Patterns of linear growth and skeletal maturation from birth to 18 years of age in overweight young adults

To estimate differences in skeletal maturity and stature from birth to age 18 years between individuals who are overweight vs normal weight in young adulthood. Weight, length and height, and relative skeletal age (skeletal-chronological age) were assessed annually from birth to age 18 years in 521 subjects (255 women) in the Fels Longitudinal Study who were overweight or obese (body mass index (BMI) >25 kg m(-2), n=131) or normal weight (n=390) in young adulthood (18-30 years). Generalized estimating equations were used to test for skeletal maturity and stature differences by young adult BMI status. Differences in height increased during puberty, being significant for girls at ages 10 to 12 years, and for boys at ages 11 to 13 years (P-values<0.001), with overweight or obese adults being ∼3 cm taller at those ages than normal weight adults. These differences then diminished so that by age 18 years, overweight or obese adults were not significantly different in stature to their normal weight peers. Differences in skeletal maturity were similar, but more pervasive; overweight or obese adults were more skeletally advanced throughout childhood. Skeletal maturity differences peaked at chronological age 12 in boys and 14 in girls (P-values<0.001), with overweight or obese adults being ∼1 year more advanced than normal weight adults. This descriptive study is the first to track advanced skeletal maturity and linear growth acceleration throughout infancy, childhood and adolescence in individuals who become overweight, showing that differences occur primarily around the time of the pubertal growth spurt. Increased BMI in children on a path to becoming overweight adults precedes an advancement in skeletal development and subsequently tall stature during puberty. Further work is required to assess the predictive value of accelerated pubertal height growth for assessing obesity risk in a variety of populations.

Cow milk consumption, insulin‐like growth factor‐I, and human biology: A life history approach

To assess the life history consequences of cow milk consumption at different stages in early life (prenatal to adolescence), especially with regard to linear growth and age at menarche and the role of insulin-like growth factor I (IGF-I) in mediating a relationship among milk, growth and development, and long-term biological outcomes. United States National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004 and review of existing literature. The literature tends to support milk's role in enhancing growth early in life (prior to age 5 years), but there is less support for this relationship during middle childhood. Milk has been associated with early menarche and with acceleration of linear growth in adolescence. NHANES data show a positive relationship between milk intake and linear growth in early childhood and adolescence, but not middle childhood, a period of relatively slow growth. IGF-I is a candidate bioactive molecule linking milk consumption to more rapid growth and development, although the mechanism by which it may exert such effects is unknown. Routine milk consumption is an evolutionarily novel dietary behavior that has the potential to alter human life history parameters, especially vis-à-vis linear growth, which in turn may have negative long-term biological consequences.

Graves' Disease - Acceleration of Linear Growth

Graves' Disease - Acceleration of Linear Growth

Weight loss and the Effect on Stature in Children During a Residential Intervention Program

Weight loss is generally high in residential weight-loss programs but the effect of a large weight loss on linear growth is not known. We report the weight loss and the influence on linear growth in a large group of children during a residential weight-loss program focusing on nutrition and physical activity. In a longitudinal noncontrolled intervention study of 990 overweight children (540 girls) attending the weight reduction program from 1990 to 2001 for about 11 weeks (age: 10-14 years, mean BMI-standard deviation score (SDS) at enrollment: 2.83) weight and height were measured initially and after end of treatment. Weekly measurements of height and weight were performed on 138 children. The children lost on average 9.4 kg, reduced their BMI by 4.5 kg/m(2) and BMI-SDS by 0.98. In a multiple regression analysis (P < or = 0.001) weight loss was higher in boys than girls (1.7 kg), higher if the weight was higher at admission (-0.192 kg/kg at baseline) and was positively associated with duration of stay (-80 g/day). Initially the boys' BMI-SDS was higher than the girls' BMI-SDS (P < or = 0.05) but after 8 weeks of treatment the boys had lower BMI-SDS than the girls. There was no negative effect on linear growth during the treatment; on the contrary, linear growth accelerated during the stay as the average increase in height was 2.38 cm corresponding to 11.4 cm/year. In conclusion the children lost close to 1 kg/week during the stay without any negative effect on linear growth. The cause of the linear growth acceleration needs further investigation.

Measuring the benefits of growth hormone therapy in children: a role for preference-based approaches?

Recombinant human growth hormone has revolutionised the management of children with growth hormone deficiency, chronic renal insufficiency, Turner syndrome, Prader-Willi syndrome, small-for-gestational-age status, idiopathic short stature and other growth disorders...

Growth hormone axis in chronic kidney disease

Chronic kidney disease (CKD) in children is associated with dramatic changes in the growth hormone (GH) and insulin-like growth factor (IGF-1) axis, resulting in growth retardation. Moderate-to-severe growth retardation in CKD is associated with increased morbidity and mortality. Renal failure is a state of GH resistance and not GH deficiency. Some mechanisms of GH resistance are: reduced density of GH receptors in target organs, impaired GH-activated post-receptor Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling, and reduced levels of free IGF-1 due to increased inhibitory IGF-binding proteins (IGFBPs). Treatment with recombinant human growth hormone (rhGH) has been proven to be safe and efficacious in children with CKD. Even though rhGH has been shown to improve catch-up growth and to allow the child to achieve normal adult height, the final adult height is still significantly below the genetic target. Growth retardation may persist after renal transplantation due to multiple factors, such as steroid use, decreased renal function and an abnormal GH–IGF1 axis. Those below age 6 years are the ones to benefit most from transplantation in demonstrating acceleration in linear growth. Newer treatment modalities targeting the GH resistance with recombinant human IGF-1 (rhIGF-1), recombinant human IGFBP3 (rhIGFBP3) and IGFBP displacers are under investigation and may prove to be more effective in treating growth failure in CKD.

SEXUAL PRECOCITY: A HISTORICAL PERSPECTIVE AND UPDATE

Puberty is the interval in the life cycle during which the child becomes an adult. It is heralded by physical changes such as acceleration of linear growth and appearance of secondary sexual characteristics, capped by attainment of reproductive capability, and orchestrated by increases in the secretion of hypothalamic, pituitary, and gonadal hormones. This article discusses selected historical and contemporary aspects of isosexual precocious puberty, i.e., the development of sexual characteristics prior to the usual age of pubertal onset.

Growth Hormone Treatment in Short Japanese Children Born Small for Gestational Age

Recent reports have shown that high-dose growth hormone (GH) treatment in short children born with small for gestational age (SGA) resulted in a pronounced acceleration of linear growth. We describe the results of multicenter trials of recombinant human GH (rhGH) treatment in short SGA children in Japan. Two clinical studies were performed and the results were combined. Study 1 comprised 104 SGA children and study 2 comprised 61 SGA children. The patients were divided into three groups: group 1 consisted of 20 patients (13 boys and 7 girls) who received rhGH 25 µg/kg per day six or seven times per week in the first year and 50 µg/kg per day in the second year and thereafter; group 2 consisted of 48 patients (28 boys, 20 girls) who received rhGH 45/50 µg/kg per day; group 3 consisted of 44 patients (28 boys, 16 girls) who received 90/100 µg/kg per day. The mean increments in height SDS were 0.46, 0.67 and 0.94 SD in boys and 0.49, 0.79 and 0.93 SD in girls in groups 1, 2 and 3, respectively. The mean increment in height SDS at 2 years in group 3 was significantly greater than that in group 1, but it was not significantly different from that in group 2 in boys and girls. Our data demonstrated that high-dose GH administration significantly improved height velocity and height SDS in short SGA children. Additional studies are necessary to optimize a long-term GH treatment regimen and combined luteinizing hormone releasing hormone analog treatment for final height. Careful observation is also necessary to assess the metabolic effects of high-dose GH, especially on carbohydrate metabolism.

Physiological issues surrounding the performance of adolescent athletes.

More than ever, many young athletes are being encouraged to train intensely for sporting competitions from an early age. Compared with studies in adults, less is known about the physiological trainability of adolescents. The velocity of physical growth during the adolescent years makes research with a group of young athletes particularly difficult. The purpose of this review is to discuss a number of physiological issues that surround the performances of the adolescent athlete. Research has highlighted the role of growth hormone (GH) in the abrupt acceleration of linear growth that occurs during adolescence. In addition, GH has been shown to be sensitive to exercise following short term intervention studies. The reduced anaerobic power of the adolescent athlete compared with that of an adult athlete has been attributed to the intrinsic properties of the muscle that are yet to be fully understood. Resistance training studies in male adolescents, and to a lesser extent female adolescents, highlight the substantial relative strength gains that can be obtained. Aerobic trainability in young boys appears to improve markedly during the adolescent years. One of the most plausible explanations for this observation is the 'trigger hypothesis' which links increased aerobic improvements in adolescence with hormonal changes and substantial growth of the cardiorespiratory and musculoskeletal systems. Studies of aerobic trainability in adolescent girls are too scarce to be conclusive. An understanding of the impact of long term intensive training on adolescent athletes is difficult to ascertain because physical stresses vary both between and within sports. There is, however, limited evidence to suggest that 'intense' training does not impair normal growth, development or maturation. Adolescent athletes who experience rapid growth as well as large increases in training volumes may be vulnerable to overuse injuries.