Osteoprotegerin and receptor activator of the nuclear factor kappa B ligand (RANKL) in healthy pubertal girls - relationships with physical growth and classical bone turnover markers.

Osteoprotegerin (OPG) is a trap receptor for the receptor activator of the nuclear factor kappa B ligand (RANKL). We aimed to determine the OPG and free soluble RANKL (sRANKL) concentrations in girls during puberty and their relationships with pubertal stage, growth rate and serum concentrations of estradiol, as well as classical bone formation (N-terminal propeptide of type I collagen (PINP), bone-specific alkaline phosphatase (BALP), osteocalcin (OC)) and bone resorption (C-terminal telopeptide of type I collagen (CTX)) markers. The semi-longitudinal study involved 88 healthy girls, aged 11.8-13.2 years. Their weight and height were measured twice at one-year intervals. Pubertal stages were assessed using the Tanner (T) scale. Blood samples were taken at the first examination. Serum concentrations of OPG, sRANKL, CTX and BALP were determined by enzyme-linked immunosorbent assay, estradiol and PINP by radioimmunoassay and osteocalcin by immunoradiometric assay. The one-year increase in height and weight of girls in the T2 and T3 pubertal stages was greater than that of girls in the T4 stage (p=0.000, p<0.03). OPG concentrations (T2: 4.04±0.62; T3: 4.31±0.79; T4: 4.46±0.84 pmol/L) sRANKL concentrations (T2: 0.22 (IQR 0.09-0.54); T3: 0.42 (IQR 0.22-0.79); T4: 0.35 (IQR 0.16-1.04) pmol/L) and sRANKL/OPG ratios (T2: 0.05 (IQR 0.03-0.13); T3: 0.11 (IQR 0.05-0.19); T4: 0.09 (IQR 0.05-0.19) did not differ significantly between pubertal stages. Concentrations of PINP, CTX, BALP and OC were higher in girls at T3 stage than at the T4 stage (p=0.000, p=0.001, p=0.046, p=0.038; respectively). Concentrations of sRANKL and OPG did not correlate with body weight, height, growth rate, or concentrations of estradiol, PINP, CTX, BALP and OC. There were correlations between the increase in height over one year and the concentrations of PINP (r=0.499, p=0.000), CTX (r=0.311, p=0.003) and BALP (r=0.224, p=0.036), as well as of estradiol (r=-0.473, p=0.000). Unlike PINP, OC, BALP, CTX or estradiol concentrations, sRANKL and OPG concentrations do not change in girls during puberty. Neither OPG nor sRANKL concentrations correlate with somatic characteristics and classical bone turnover markers concentrations.

Height at menarche is influenced by estrogen receptor alpha gene polymorphisms.

BACKGROUND: It has been suggested that polymorphic variations in estrogen receptors (ERs) genes may have an impact on linear growth of girls during puberty. AIM: The aim of the study was to investigate whether height at menarche is influenced by PvuII and XbaI polymorphisms of the ERalpha gene. SUBJECTS AND METHODS: The study population consisted of 127 healthy girls, who were observed from premenarcheal period at six monthly intervals, until menarche occurred in all participants. Anthropometric measurements were taken at each visit and their values at menarche were calculated using centile curves drawn individually for each subject. PvuII and XbaI ERalpha gene polymorphisms were evaluated with RLFP-PCR. RESULTS: The age at menarche was not related to ERalpha gene polymorphisms. Girls with pp genotype were at menarche on average 3.2 cm shorter than PP homozygotes and in addition xx homozygotes were shorter than subjects with XX and Xx genotypes: 3.0 cm and 3.9 cm respectively. Subjects with px haplotype were, at the onset of the first menstrual period, from 2.3 cm to 3.1 cm shorter than carriers of other haplotypes. The leg length-to-height ratio at menarche was lower in xx homozygotes than in Xx heterozygotes and lower in px haplotype in comparison to Px and pX haplotypes carriers. Corresponding associations were observed at the final visit. CONCLUSIONS: Height at menarche is influenced by the ERalpha gene polymorphism.

Leptin gene expression in subcutaneous adipose tissue in girls before and during puberty.

OBJECTIVES: Leptin functions as a neuroendocrine hormone and it is related to the onset of puberty in animal models. Its role in normal human sexual maturation is still incompletely defined. The aim of the study was to assess the relationships between leptin mRNA (gene) expression, thickness of subcutaneous fat tissue and the serum concentration of leptin in girls before and during puberty. STUDY DESIGN: Twenty-nine lean girls were studied (mean age 10.8+/-1.9 years). The subjects were divided into two groups according to pubertal status. The first group consisted of 14 prepubertal girls and second group of 15 girls who were in puberty. Body height, weight, arm circumference, skin fold thickness at abdominal, triceps and subscapular sites were measured. Serum leptin was assessed by RIA method. Leptin mRNA was measured in subcutaneous abdominal adipose tissue by semi-quantitative assays based on reverse transcription (RT) of the mRNA and polymerase chain reaction (PCR) amplification of the cDNA. RESULTS: Girls in pubertal stages had higher serum leptin concentration than prepubertal girls. The mean values of leptin mRNA level in subcutaneous abdominal adipose tissue were not statistically different between groups. There was also no difference between the thickness of skin folds in investigated girls. A positive correlation between leptin mRNA expression and skin fold thickness, BMI and arm circumference as well as between the leptin concentration and skin fold thickness, BMI and arm circumference were observed. CONCLUSIONS: The level of leptin gene expression and serum leptin concentrations depend on the amount of fat tissue. We can propose that initiation of pubertal events does not result from increased of leptin mRNA expression in subcutaneous abdominal fat cells or from its increased concentration in blood.

Association between leptin, markers of bone formation and physical growth of newborns.

BACKGROUND: The increase of body size and weight depends on metabolism in the bone tissue and accumulation of fat, but the role of many hormones and enzymatic systems that may influence these processes significantly has not been recognized. AIM: An attempt to assess the correlation between the leptin hormone taking part in the regulation of fat tissue reserves, markers of bone formation and selected anthropometric traits in newborns was made. SUBJECTS AND METHODS: Levels of leptin, osteocalcin and C-terminal propeptide type I procollagen (PICP) in the serum of 64 Appropriate for Gestational Age newborns (AGA newborns) with gestational age between 27 and 42 weeks were assessed. In parallel, 15 anthropometric traits were measured and the Quetelet Index was calculated for all the newborns. Statistical analysis was performed using the Student's t-test, Mann-Whitney U test, Pearson's correlation and Spearman's correlation rank test. p < 0.05 was regarded as significant. RESULTS: Statistically significant correlations between leptin, osteocalcin, PICP and selected anthropometric traits in newborns were found. There were no statistically significant correlations between serum levels of leptin and markers of bone formation in the investigated group of children. CONCLUSION: In our study, we documented the association of leptin, osteocalcin and PICP with overall physical growth of AGA newborns. We did not confirm the relationship between leptin and bone formation in this stage of ontogenesis.

[Leptin as a trigger for puberty in girls]. / Leptyna jako czynnik wywolujacy pokwitanie u dziewczat.

UNLABELLED: The influence of leptin on the serum levels of follicle stimulating hormone (FSH) and estradiol in girls during puberty was longitudinally studied. Two hundred and twenty-seven healthy girls aged from 8.8 to 15.4 years were included in the study. After physical examination, girls were divided into four groups according to pubertal development. Body fat was assessed using body mass index and the sum of three skin folds: at the triceps site, subscapular site and on abdomen. Serum concentration of leptin, FSH and estradiol were assessed by RIA methods. RESULTS: The mean serum concentration of leptin, FSH and estradiol increase progressively throughout puberty. Leptin strongly correlates with the thicknesses of the skin folds and BMI but small significant positive correlations were found between leptin and FSH as well between leptin and estradiol.

[Child abuse as a problem of the family physician]. / Krzywdzenie dziecka jako problem lekarza rodzinnego.

There are four major forms of child abuse: physical abuse, emotional abuse, sexual abuse and neglect. Various combination of these four aspects often exists in the individual child and clinical manifestation can not be so clear-cut. In this paper the authors present some problems of child abuse syndrome (taking into consideration risk factors, clinical symptoms, recognition and methods of treatment) whose knowledge may be helpful for the family doctor who comes into contact with such children.

[The role of dehydroepiandrosterone sulfate during puberty in girls]. / Rola siarczanu dehydroepiandrosteronu w pokwitaniu u dziewczat.

OBJECTIVES: The serum concentration of dehydroepiandrosterone sulfate (DHEAS) in relation to serum levels of follicle stimulating hormone, estradiol, insulin-like growth factor I (IGF-I) and height and weight velocity in girls during puberty were studied. MATERIAL AND METHODS: One hundred and forty nine healthy girls aged from 9.8 to 14.7 years were divided, after physical examination, into four groups according to pubertal development. Serum concentration of DHEAS, FSH, estradiol, cortisol and IGF-I were assessed by RIA methods. One hundred and thirteen girls were examined anthropometrically again and annual increases of body height and weight were analysed concomitantly with DHEAS concentration. RESULTS: The mean serum concentration of DHEAS, FSH, estradiol and IGF-I increase progressively throughout puberty, while cortisol concentration remains constant. Positive correlation was found between DHEAS and FSH as well as between DHEAS and estradiol and IGF-I concentration. No correlation was found between DHEAS and growth velocity. CONCLUSIONS: DHEAS might play an important role during girls puberty although its exact role is very difficult to establish because this steroid works mainly as a precursor for both estrogen and androgen formation.

[The influence of IGF-1 on the biosynthesis of type I and III colagen during puberty]. / Wplyw IGF-I na synteze kolagenu typu I i III w okresie pokwitania.

OBJECTIVES: The influence of insulin-like growth factor I (IGF-I) on the biosynthesis of type I and III collagen during puberty was studied. MATERIAL AND METHODS: Eighty-four healthy girls aged from 9.8 to 14.7 years were included into this study. After careful physical examination all girls were divided into three groups according to pubertal development. To assess pubertal stage we performed breast examination according to Tanner (bd). Group I consisted of 26 girls in prepubertal stage (1 of bd); group II (stage 2 and 3 of bd) 29 girls, and group III (stage 4 and 5 of bd)--27 girls. Serum concentration of PICP (C-terminal propeptide of type I collagen), PIIINP (N-terminal propeptide of type III collagen, as well as IGF-I were assessed by RIA methods. RESULTS: The highest mean values of serum PICP and PIIINP were found in girls in the second group (stage 2 and 3 of bd) whereas the lowest values were observed in group III (stage 4 and 5 of bd). The mean serum concentration of IGF-I presented a steady increase as puberty advanced being highest in girls in group III. No correlation was found between IGF-I and PICP and IGF-I and PIIINP. A positive correlation were observed between mean serum concentration of IGF-I and age (R = 0.52; p < 0.0001), height (R = 0.51; p < 0.0001), and body weight (R = 0.47; p < 0.0001) in investigated groups. CONCLUSIONS: Although IGF-I showed a steady increase during puberty no correlation was observed between its serum concentration and markers of collagen biosynthesis (PICP and PIIINP).

Serum leptin concentrations in women taking oral contraceptives.

OBJECTIVES: To investigate serum leptin concentrations in women taking oral contraceptives containing the same gestagen and different doses of ethinyl estradiol. STUDY DESIGN: 30 women received tablets containing 20 microg of ethinyl estradiol (EE) and 150 microg of desogestrel (DSG) (Mercilon) whereas another group of 30 women received 30 microg of EE and 150 microg of DSG (Marvelon). Serum leptin concentrations were estimated using a Leptin RIA kit (Linco Research USA) after an overnight fast on the first day of the cycle prior to the onset of therapy as well as after the 3rd and 6th treated cycles. RESULTS: In both groups a positive correlation between serum leptin and body mass index (BMI) was found (r=0.56; P<0.001 and r=0.67; P<0.001). The initial serum leptin concentration in the Mercilon group was 7.62+/-8.46 ng/ml. This value was not statistically different from values after 3 months (9.31 8.23 ng/ml) and after 6 months (10.53+/-8.03 ng/ml) of treatment. Very similar results were found in patients receiving Marvelon: 8.81+/-6.56 ng/ml initially; 11.62+/-11.16 ng/ml at 3 months, and 10.38+/-7.32 ng/ml at 6 months. The statistical analysis did not reveal any significant difference at each investigated time point in either study group. CONCLUSIONS: Modern low dose OC containing third generation gestagen and low dose of ethinyl estradiol, does not have any influence on serum leptin or BMI, and therefore does not exert a significant influence on body energy metabolism.

[Serum leptin ++ concentration in fetal and maternal compartments]. / Stezenie leptyny w krwi matczynej i plodowej w ciazy donoszonej.

OBJECTIVES: Presumable role of leptin, the product of ob gene, is signalling the energy stores to the brain. Moreover, leptin is also responsible for the food intake through the influence on the appetite. Since the fetal energy metabolism is strongly dependent on maternal nutritional health, leptin should be of peculiar importance during pregnancy. MATERIAL AND METHODS: Fifteen full-term pregnant women (mean age 27.5 +/- 6.4 years; mean gestational age 39.2 +/- 2.5 weeks; mean parity 2.1 +/- 0.9) were enrolled into the study. Immediately after delivery blood was taken from mother antecubital vein and from the umbilical cord vessels (vein and artery). Leptin concentrations in the sera were estimated by the RIA method using Linco Research Human Kit-USA. RESULTS: The highest mean serum leptin concentration was found in maternal compartment (21.9 +/- 12.9 ng/ml) and this value was significantly higher than observed in umbilical artery 4.36 +/- 2.65 ng/ml; p < 0.001). The leptin concentration in umbilical vein was 13.1 +/- 10.7 ng/ml and this value was not statistically different than concentration found in umbilical artery (p = 0.054) and mother antecubital vein (p = 0.1). A strong positive correlation was found between maternal serum leptin concentration and maternal body mass (r = 0.5; p < 0.001) and between fetal umbilical artery leptin concentration and newborn body mass (r = 0.7; p < 0.0001). CONCLUSIONS: Among full term pregnant women strong positive correlation between serum leptin concentration and body mass was found. Even better correlation was observed between umbilical artery leptin concentration and newborn body mass. Relatively big serum leptin concentration gradient between mother and umbilical vessels indicates that placenta might play an important role in leptin production.