leptin and Puberty--Precocious

The term precocious puberty encompasses a group of heterogeneous conditions that range from variants of normal to slowly progressive and rapidly progressive maturation of both sexes. It is defined as the appearance of secondary sex characteristics before the age of 8 in girls and 9 in boys. The clinician who is evaluating a child with precocious puberty should be aware of the normal events of puberty, the ages at which pubertal milestones are achieved and the tempo of pubertal progression. The mechanisms involved in the onset and progression of normal puberty are briefly discussed in this article. The diverse etiology of precocious puberty, the diagnostic evaluation of the patient including clinical, laboratory and radiological investigation as well as problems associated with precocious puberty and indications for treatment and treatment modalities are further discussed in the article.

Topics: Animals; Body Height; Bone and Bones; Child; Estrogen Receptor Modulators; Female; Gonadotropin-Releasing Hormone; Humans; Leptin; Male; Puberty, Precocious; Rats; Receptors, G-Protein-Coupled

The fundamental aspects of the hypothalamic luteinizing hormone-releasing hormone (LHRH)(1) [1]pulse generator-pituitary gonadotrophin-gonadal apparatus in mammals have striking commonalities. There are, however, critical, substantive differences in the neuroendocrinology of puberty among species. The onset of puberty in the human is marked by an increase in the amplitude of LH pulses, an indirect indicator of the increase in amplitude of LHRH pulses. The hypothalamic LHRH-pituitary gonadotrophin complex is functional by at least 0.3 gestation in the human foetus; the sex difference in the fetal and neonatal pattern of LH and FSH secretion is an apparent consequence of imprinting of the fetal hypothalamus-pituitary-gonadotropin apparatus by fetal testosterone. Until about 6 months of age in boys and 12-24 months in girls, the testes and ovaries respond to the increased LH in boys and follicle-stimulating hormone (FSH) in girls by secreting testosterone and oestradiol, respectively, reaching levels that are not again achieved before the onset of puberty. Striking features of the ontogeny of the human hypothalamic pulse generator are: (1) its development and function in the foetus; (2) the continued function of the hypothalamic LHRH pulse generator-pituitary gonadotrophin-gonadal axis in infancy; (3) the gradual damping of hypothalamic LHRH oscillator activity during late infancy; (4) its quiescence during childhood - the so-called juvenile pause; (5) during late childhood the gradual disinhibition and reactivation of the LHRH pulse generator, mainly at night; (6) the increasing amplitude of the LHRH pulses, which are reflected in the progressively increased and changing pattern of circulating LH pulses, with the approach of and during puberty. The intrinsic central nervous system (CNS) mechanisms responsible for the inhibition of the LHRH pulse generator during childhood (the juvenile phase) involve the major role of an inhibitory neuronal system - the CNS inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and GABAergic neurons, as revealed by studies in the rhesus monkey by Terasawa and her associates. With the onset of puberty, the disinhibition and reactivation of the LHRH pulse generator is associated with a fall in GABAergic neurotransmission and a concomitant increase in the input of excitatory amino acid neurotransmitters (including glutamate) and possibly astroglial-derived growth factors. Despite remarkable progress over the past three dec

Topics: Animals; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Gonads; Humans; Hypothalamo-Hypophyseal System; Leptin; Luteinizing Hormone; Male; Neurosecretory Systems; Neurotransmitter Agents; Pituitary-Adrenal System; Progesterone; Puberty; Puberty, Precocious; Testosterone; Turner Syndrome

To compare the serum inhibin B, anti-Müllerian hormone (AMH) and leptin concentrations in girls with idiopathic central precocious puberty (CPP) to their concomitant characteristics and evaluate the capacity of each of these hormones to predict the age at first menstruation in those who were untreated and who completed their puberty.. This single-center study included 94 girls selected from a cohort of 493 girls seen between 1981 and 2012 and diagnosed with idiopathic CPP for whom a remaining serum sample collected at the initial evaluation was available. Of these 25 were untreated and completed their puberty.. In the whole cohort the inhibin B concentration displayed significant positive correlations with the age at the onset of puberty and at initial evaluation; bone age; breast Tanner stage; serum basal estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and AMH concentrations, LH peak and LH/FSH peak ratio. The AMH concentration displayed a significant positive correlation with serum estradiol and a negative correlation with basal FSH concentration. The leptin concentration displayed significant positive correlations with the age at initial evaluation, bone age, and body mass index and a negative correlation with the FSH peak.. In 25 untreated girls, the inhibin B concentration was negatively correlated with the age at first menstruation (r = -0.61, p = 0.001) and the time between the onset of puberty and first menstruation (r = -0.59, p = 0.002). Inhibin B concentrations <30 pg/mL were associated with a time between the onset of puberty and first menstruation ≥3 years in 14/15 patients with a sensitivity of 0.67 and a specificity of 0.75. The age at first menstruation was estimated using a formula: min (11.15-0.510 LH/FSH peak ratio, 11.57-0.025 inhibin B)available at: http://www.kamick.org/lemaire/med/girls-cpp18.html.. We established formulas based on the serum inhibin B concentrations and LH/FSH peak ratio at the initial evaluation, alone or in combination, to predict the age at first menstruation in girls with CPP. These formulas can assist with determining the indications for treatment in CPP.

Topics: Child; Estradiol; Female; Follicle Stimulating Hormone; Humans; Inhibins; Leptin; Luteinizing Hormone; Menstruation; Puberty, Precocious; Retrospective Studies

Puberty is part of a critical window in which adiposity and its correlates can be fine-tuned toward reproduction, which implies that puberty provides an opportunity to reprogram a misprogramming that occurred in early life. We tested this hypothesis in low-birthweight (LBW) girls with precocious pubarche (PP), who are at risk for hyperinsulinemic body adiposity during and beyond puberty.. LBW girls with PP (n = 38; mean age 8 years) were randomized to remain untreated or to receive metformin across puberty (425 mg/d for 2 years, then 850 mg/d for 2 years); subsequently, all girls were monitored for 1 year without intervention. Here we report on the latter year.. The benefits of metformin were mostly maintained during the posttreatment year so that, after 5 years, metformin therapy was associated with more lean mass; with less total, visceral, and hepatic fat; with lower circulating levels of androgens and leptin; and with elevated levels of high-molecular-weight adiponectin and undercarboxylated osteocalcin.. In LBW girls with PP, pubertal metformin therapy was followed by a favorable adipokine profile and by a reduction of total, visceral, and hepatic adiposity beyond puberty.

Topics: Adiposity; Adolescent; Body Weight; Child; Comorbidity; Female; Follow-Up Studies; Humans; Hyperinsulinism; Hypoglycemic Agents; Infant, Low Birth Weight; Infant, Newborn; Intra-Abdominal Fat; Leptin; Liver; Magnetic Resonance Imaging; Metformin; Puberty, Precocious

Leptin can be regarded as a marker of the nutritional status of the body. This study was performed to determine the correlation of leptin levels with insulin (I) and androgens in girls with premature pubarche (PP) and prepubertal controls (C) with (OB) or without (nOB) obesity. We studied 25 girls with PP and 14 C; girls were dived into two subgroups according to body mass index (BMI): OB (18 PP and 8 C) and nOB (7 PP and 6 C). Obesity was defined as BMI >95th percentile for chronological age. Serum levels of leptin, I, glucose (G), DHEAS, testosterone, androstenedione (A), cortisol, SHBG, IGFBP-1 and lipid profile were measured. The fasting G to I ratio (FGIR) was calculated and FGIR <7 was considered as suggestive of I resistance (IR). Data were analyzed comparing PP vs C and OB vs nOB. Serum DHEAS (0.60 +/- 0.45 vs 0.18 +/- 0.22 microg/ml) and A (895.5 +/- 420.4 vs 457.0 +/- 352.1 pg/ml) levels were significantly higher in PP than C. Other hormonal and metabolic parameters were similar. Serum leptin (30.8 +/- 18.3 vs 8.1 +/- 5.9 ng/ml), A (841.8 +/- 471.1 vs 522.5 +/- 317.2 pg/ml), DHEAS (0.53 +/- 0.44 vs 0.31 +/- 0.39 microg/ml), G (88.4 +/- 8.8 vs 80.2 +/- 8.1 mg/dl), I (13.5 +/- 7.7 vs 5.1 +/- 3.7 microU/ml) and total cholesterol (TC) (180.5 +/- 30.9 vs 161.8 +/- 29.5 mg/dl) levels were greater in the OB than in the nOB group. IR was observed in 10 girls with OB and in one with nOB. Leptin was correlated with BMI (r = 0.83), SHBG (r = -0.44), IGFBP-1 (r = -0.47), I (r = 0.37), A (r = 0.48) and TC (r = 0.36), but in multiple regression analysis only with BMI (r2 = 0.72, p < 0.001). Girls with PP and prepubertal OB girls showed elevated leptin levels independent of I and androgen levels. Girls with OB had a greater degree of hyperandrogenism and IR. As obesity, IR and hyperandrogenism are common findings in polycystic ovary syndrome (PCOS), which is more prevalent in young women with a history of PP, a role of leptin in PCOS can be suggested. In addition, girls with PP could be considered a population at risk for plurimetabolic syndrome.

Topics: Androgens; Blood Glucose; Body Mass Index; Child; Dehydroepiandrosterone Sulfate; Female; Humans; Insulin; Insulin Resistance; Leptin; Lipids; Obesity; Puberty, Precocious; Reference Values

Since hyperandrogenism in simple obesity is assumed to arise from hyperinsulinism and/or increased insulin-like growth factor I (IGF-I) or leptin levels, we examined how in patients with Prader-Willi syndrome (PWS), the most frequent form of syndromal obesity, the accelerated adrenarche can be explained despite hypothalamic-pituitary insufficiency with low levels of insulin and IGF-I.. In 23 children with PWS and a mean age of 5.6 years, height, weight, fat mass, fasting insulin concentration, insulin resistance (by HOMA-R; see text), and leptin and IGF-I levels were determined to test whether they explain the variance of the levels of dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), of androstenedione, and of cortisol before and during 42 months of therapy with growth hormone.. The baseline DHEAS, DHEA, and androstenedione concentrations were increased as compared with age-related reference values, whereas the cortisol level was always normal. During growth hormone treatment, the DHEA concentration further rose, and the cortisol level decreased significantly. The insulin and IGF-I concentrations were low before therapy, while fat mass and leptin level were elevated. The hormonal covariates provided alone or together between 24 and 60% of the explanation for the variance of adrenal androgen levels, but the anthropometric variables did not correlate with them.. In children with PWS, elevated androgen levels correlate with hormones that are usually associated with adiposity. However, the lack of direct correlations between disturbed body composition and androgen levels as well as the increased sensitivity to insulin and IGF-I are abnormalities specific to PWS, potentially caused by the underlying hypothalamic defect.

Topics: Adolescent; Adrenal Glands; Analysis of Variance; Androgens; Androstenedione; Anthropometry; Body Composition; Child; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Growth Hormone; Hormone Replacement Therapy; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Male; Obesity; Prader-Willi Syndrome; Prospective Studies; Puberty, Precocious

Leptin is a metabolic signal that may be involved in signaling adequacy of energy metabolism for the onset of reproductive function. The aim of this study was to investigate the relationship between leptin serum levels and pubertal development in girls with progressive central precocious puberty (CPP). We investigated longitudinally 14 girls with CPP before and during treatment with depot leuprorelin acetate. Mean (+/-SEM) chronological age and bone age at start of therapy were 6.0+/-0.6 y and 9.5+/-0.7 y, respectively. Leptin was determined by RIA. Girls with CPP showed no significant difference in leptin levels at pretreatment and after 1 and 2 y of treatment compared with healthy girls of the same body mass index (BMI). Mean leptin SD score adjusted for BMI was 0.31+/-0.4, 0.24+/-0.2, and 0.49+/-0.3, respectively (not significant). In a stepwise regression analysis model with BMI, bone age, chronological age, basal and stimulated LH, estradiol, dehydroepiandrosterone, androstenedione, and clinical pubertal signs, BMI was the only parameter that showed a significant correlation with leptin (p = 0.006). In conclusion, these data suggest that serum leptin levels are not significantly elevated at the onset of CPP compared with normal girls. Treatment with depot gonadotropin releasing hormone agonist seems to have no influence on leptin concentrations. As in normal girls, serum leptin levels in girls with CPP are mainly determined by BMI. Thus, we have no evidence that alterations of leptin are related to premature onset of puberty.

Topics: Androstenedione; Body Height; Body Mass Index; Child; Child, Preschool; Dehydroepiandrosterone; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Leptin; Leuprolide; Luteinizing Hormone; Proteins; Puberty, Precocious; Radioimmunoassay; Reference Values

Precocious puberty (PP) has increasingly become a social concern. This study aimed to investigate the effect of timosaponin AIII (TAIII) on the precocious puberty and its possible mechanisms in mice. Four groups of mice consisting of controls that received saline or TAIII, a model that received leptin to induce precocious puberty (PP), and leptin+TAIII (the leptin model treated with TAIII) were used to determine the effect of TAIII on PP. Pathological and cytological examinations were conducted to investigate the signs and onset of PP and the development of reproductive organs. The level of serum luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E2) were determined using enzyme-linked immunosorbent assay (ELISA). The expression of genes related to the hypothalamic-pituitary-gonadal axis (HPGA) was assessed using qRT-PCR and Western blotting. Bone mineral density (BMD) was determined using high resolution peripheral quantitative computed tomography. In mice treated with leptin, earlier vaginal opening and estrus were observed, as well as the increased ovarian and uterine weight, total uterine cross-sectional size, number of corpora lutea, and elevated serum sex hormone levels and HPGA expression. On the other hand, TAIII treatment delayed the vaginal opening and vaginal estrus to 32.1 and 37.5 days after birth, and delayed the development of reproductive organs, leading to significantly smaller uterus and ovary size, less corpora lutea and low BMD (P<0.05). In addition, the serum levels of LH, FSH and E2 were significantly reduced (P<0.05) and so was the expression of HPGA and leptin genes (P<0.05). Our experimental data demonstrated that TAIII has activity against leptin-induced PP activity and may attenuate PP by reducing reproductive hormones and deactivating the hypothalamic-pituitary-gonadal axis through downregulating leptin expression.

Topics: Animals; Female; Follicle Stimulating Hormone; Hypothalamic-Pituitary-Gonadal Axis; Leptin; Luteinizing Hormone; Mice; Puberty, Precocious; Saponins

To determine if the leptin, adiponectin, and leptin/adiponectin ratio (LAR) can predict weight gain at the end of GnRH analogs (GnRHa) treatment in girls with central precocious puberty (CPP).. Study design: prospective cohort. Serum levels of leptin and adiponectin were determined at diagnosis of CPP. Anthropometry was performed at diagnosis of CPP and every six-months, until treatment with GnRHa was discontinued and they presented menarche. Patients were divided according to BMI<94 and BMI>95 percentile at diagnosis of CPP. The outcome was the increased in weight gain (e.g., from normal weight to overweight) at the end of follow-up. Statistical analysis: repeated measures ANOVA test and Student's t-test were used to compare groups. Logistic regression analysis was used to evaluate the association of leptin and adiponectin levels, as well as LAR values with increased weight gain.. In patients with CPP, leptin levels and higher LAR values appear to be associated with significantly greater weight gain during GhRHa treatment, particularly in girls starting with BMI < 94 percentile.

Topics: Adiponectin; Body Mass Index; Female; Humans; Leptin; Overweight; Prognosis; Prospective Studies; Puberty, Precocious; Weight Gain

The purpose of this study is to explore the related factors of precocious puberty in children.. 1239 children who underwent physical examination in our hospital from January 2020 to December 2022 were analyzed, including 198 precocious children and 1041 normal children. According to the age of 198 precocious children and 1041 normal children, 205 normal children were selected, and the remaining 836 normal children were excluded. They were divided into precocious group and normal group. The general data of the two groups were recorded. Logistic regression was used to analyze the influencing factors of precocious puberty in children.. There were statistically significant differences (P < 0.05) between the two groups in sex, bone age, daily exercise time, E2, FSH, LH, leptin, mother's menarche time, living environment, consumption of nutritional supplements, consumption of foods containing pigments and preservatives, consumption of high-protein foods, and sleeping time. The multifactor logistic regression analysis shows that the risk factors of children's precocious puberty included gender (female), bone age (> 10 years old), and daily exercise time (< 0.9 h), E2 (≥ 66.00pmol/L), FSH (≥ 6.00U/L), LH (≥ 3.50U/L), leptin (≥ 8.00 µ G/L), mother's menarche time (< 12 years old), living environment (chemical industry zone), consumption of nutritional supplements (often), consumption of high-protein food (often), and sleep time (< 10 h).. In conclusion, children's gender, bone age, exercise habits, E2, FSH, LH, leptin, mother's menarche time, living environment, eating habits, sleep time and other factors are closely related to precocious puberty in children. Reminding parents to actively prevent related factors in clinical work is helpful to prevent the occurrence of precocious puberty in children.

Topics: Child; Dietary Supplements; Female; Follicle Stimulating Hormone; Humans; Leptin; Puberty, Precocious; Risk Factors

This study was an attempt to examine the changes in serum levels of ghrelin and leptin after 12-weeks of aerobic training and gonadotropin releasing hormone agonist (GnRH) treatment in girls with central precocious puberty. Thirty girls (6-8 years old) with precocious puberty who had received Triptorelin were randomly divided in two groups (medication and medication + training). Fifteen age-matched healthy girls (without precocious puberty) were also included as the control group. The medication + training group submitted an aerobic training program for 3 days/week with 20-75 min per day and 45-75% of maximum heart rate for 12-weeks. Serum levels of leptin, ghrelin, cholesterol, triglycerides and body mass index (BMI) were determined at baseline and 48 h after the last training session. The results indicated that leptin significantly decreased (p = 0.001) and ghrelin significantly increased (p = 0.001) in the medication + training group but no significant difference was observed in the ghrelin (p = 1) and leptin (p = 0.78) in the medication group. Leptin to ghrelin ratio indicated a decrease in medicine + training group (p = 0.028). Ghrelin were negatively correlated with leptin and BMI. The data indicated that aerobic training increased ghrelin and reduced leptin and leptin to ghrelin ratio but GnRH agonist treatment had no effect on plasma leptin and ghrelin levels.

Topics: Body Mass Index; Child; Female; Ghrelin; Humans; Leptin; Puberty, Precocious; Triptorelin Pamoate

This paper aims to investigate the correlation between serum levels of luteinizing hormone (LH), insulin-like growth factor-1 (IGF-1) and leptin and the incidence of idiopathic central precocious puberty (ICPP) in girls, and to explore the clinical values in the diagnosis of ICPP.. A total of 48 girls with ICPP were selected in our hospital from March 2014 to March 2015 to serve as ICPP group. At the same time, 48 girls with the same age distribution were selected as control group. Bone age, body weight, Body Mass Index (BMI) and gender development index of girls in each group were recorded. Levels of LH, IGF-1 and leptin in serum were measured by chemiluminescence immunoassay. The correlations within levels of LH, IGF-1 and leptin, and the correlations between levels of LH, IGF-1 and leptin and body height, body weight and gender development index were analyzed.. Levels of LH, IGF-1 and leptin in ICPP group were significantly higher than those in control group (P<0.01). Body weight and BMI of ICPP group were significantly higher than those of control group (P<0.01), and were positively correlated with the expression level of leptin; ovarian volume and thickness of breast of ICPP group were significantly higher than those of control group (P<0.01), and were positively correlated with serum level of LH; serum level of IGF-1 was positively correlated with bone age. Levels of LH, IGF-1 and leptin in serum of ICPP girls were all increased compared with control group.. LH peak value and levels of IGF-1 and leptin in serum can be used as diagnostic indexes of ICPP.

Topics: Body Weight; Female; Humans; Insulin-Like Growth Factor I; Leptin; Luteinizing Hormone; Puberty, Precocious

The aim of this study was to examine the hormonal profile in early-pubertal girls with obesity. We hypothesized that these patients might already present hormonal alterations with POCS-like features.. Cross-sectional study in a sample of 283 peri-pubertal girls (prepubertal and early-puberty subgroups), aged 6.1-12.0 years, diagnosed with obesity (BMI-SDS > 2.0, 97th percentile), so-called obesity group. They all underwent clinical examination and blood testing for hormonal measurements (leptin, TSH, FT4, IGF-1, IGFBP3, prolactin, insulin, FSH, LH, estradiol, ACTH, cortisol, 17-OH-P, DHE-S, androstenedione, testosterone and free testosterone). A control group was recruited: 243 healthy girls, aged 6.3-12.1 years, with normal BMI status.. Prepubertal girls with obesity had significantly higher values (p < 0.05) for BMI-SDS, leptin, insulin and HOMA-IR levels than control group. Early-pubertal girls with obesity also had significantly higher values (p < 0.05) for BMI-SDS, leptin, IGF-1, IGFBP3, insulin and HOMA-IR, LH, ratio LH/FSH, ACTH, DHE-S, androstenedione, testosterone and free testosterone levels than control group. In early-pubertal girls with obesity (not prepubertal girls), there was a positive correlation (p < 0.01) between leptin levels with LH, androstenedione and testosterone, and HOMA-IR with LH and testosterone levels. There was also a positive correlation (p < 0.01) between IGF-1 levels with LH, androstenedione, DHE-S and testosterone; and LH levels with testosterone.. The results obtained support our hypothesis that an abnormal hormonal profile with POCS-like features can already be detected (insulin resistance and hyperinsulinemia, increased secretion of LH and ACTH, and overproduction of ovarian and adrenal androgens) in early-pubertal girls with obesity.

Topics: Adrenocorticotropic Hormone; Androgens; Androstenedione; Cross-Sectional Studies; Female; Follicle Stimulating Hormone; Humans; Insulin; Insulin-Like Growth Factor I; Leptin; Obesity; Puberty; Puberty, Precocious; Testosterone

Premature pubarche (PP) is a risk factor for metabolic syndrome (MS). The aim was to evaluate if glucose-insulin metabolism, cardiovascular risk factors, familial cardiovascular risk factors (FCVRF) created a risk for insulin resistance (IR) and if PP was a risk factor alone for MS in normal weight prepubertal girls with PP.. Thirty-five prepubertal, non-obese girls with PP with normal birth weight and 35 age-matched control girls were evaluated for FCVRF, anthropometric measurements, blood pressure, lipid profile, fasting blood glucose-insulin, hemoglobin A1c (HbA1c), sex hormone binding globulin (SHBG), leptin, adiponectin, tumor necrosis factor-alpha (TNF-α), androgen levels, and bone age. Oral glucose tolerance test was performed in PP participants. Homeostasis model of assessment of IR (HOMA-IR), fasting glucose/insulin ratio, atherogenic index (AI), and free androgen index (FAI) were calculated. PP participants were further stratified by FCVRF.. HbA1c, lipid profile, testosterone, leptin, adiponectin, TNF-α, HOMA-IR, glucose/insulin ratio, AI, and fasting glucose-insulin levels were similar. In the PP group FAI was significantly higher (p=0.001), whereas SHBG was significantly lower (p=0.010) than the control group. Leptin levels of FCVRF+ and FCVRF- subgroups were 15.2±9.1 and 9.7±7.2 ng/mL, respectively and the difference was significant (p=0.016).. As PP does not appear to be a risk factor alone for impaired glucose metabolism and IR in prepubertal non-obese girls with normal birth weight, it is our opinion that it is unnecessary to examine in detail such cases before puberty. Low SHBG levels in the PP group and high leptin levels in FCVRF+ subgroup might suggest that these may be predictive for MS in the future.

Topics: Adiponectin; Androgens; Birth Weight; Blood Glucose; Cardiovascular Diseases; Female; Glucose; Glycated Hemoglobin; Heart Disease Risk Factors; Humans; Insulin; Insulin Resistance; Leptin; Lipids; Metabolic Syndrome; Puberty, Precocious; Risk Factors; Tumor Necrosis Factor-alpha

To analyze the diagnostic value of luteinizing hormone (LH) peak value of the gonadotropin-releasing hormone (GnRH) stimulation test for girls with precocious puberty and its correlation with body mass index (BMI).. A total of 230 girls with precocious puberty who came to our hospital for testing from June 2019 to June 2021 were selected and divided into a true group (. There were no significant differences in age and breast stage between the true group and the sham group (. The LH peak value of the GnRH stimulation test has high diagnostic value for girls with precocious puberty, and BMI is negatively correlated with the LH peak value of CPP children.

Topics: Body Mass Index; Child; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Leptin; Luteinizing Hormone; Obesity; Overweight; Puberty, Precocious

Reducing the mean age of puberty onset in recent years has crucial public health, clinical, and social implications. This study aimed to evaluate the serum levels of appetite-related peptides (leptin, ghrelin, nesfatin-1, and orexin-A) and anthropometric data in girls with premature thelarche (PT).. We enrolled 44 girls aged 4-8 years diagnosed with PT and 33 age-matched healthy girls as controls. The demographic data of the girls were obtained using a questionnaire. Anthropometric data were measured and fasting blood samples were collected.. Body weight, height, body mass index (BMI), body fat mass, and basal metabolic rate (BMR) were higher in the PT group than in the control group (p < 0.05). Serum leptin (p < 0.001), nesfatin-1 (p = 0.001), and orxein-A (p < 0.001) levels were significantly higher in the PT group than in healthy controls. However, there were no significant differences in the serum ghrelin levels between the groups (p > 0.05). The results of multivariate logistic regression revealed that serum leptin level (OR (95% CI): 42.0 (10.91, 173.06), p < 0.001), orexin-A (OR (95% CI): 1.14 (1.04, 1.24), p = 0.006), and BMI for age z-score (OR (95% CI): 6.97 (1.47, 33.4), p = 0.014) elevated the risk of incidence of PT at 4-8 girls.. These results suggest that in addition to serum leptin levels, serum orexin-A and nesaftin-1 can take part in the initiation of PT. Few studies have investigated the relationship between nesfatin-1 and orexin-A levels and age at onset of puberty; hence, it should be a subject for future studies.

Topics: Body Mass Index; Female; Ghrelin; Humans; Leptin; Orexins; Puberty, Precocious

To determine appetite-regulating hormone levels in girls with central precocious puberty (CPP) before and after 20 weeks of gonadotropin-releasing hormone analogue (GnRH-A) treatment.. Eighteen newly diagnosed CPP girls were enrolled. Body composition measured by bioelectrical impedance analysis and GnRH-A test were performed with fasting serum leptin, ghrelin and peptide YY (PYY) measurements at baseline (before) and after 20 weeks of GnRH-A treatment.. Decreased estrogen following short-term GnRH-A treatment in CPP girls may cause an increase in appetite and consequently an elevation of FMI. Increased serum leptin may be a result of having increased FMI secondary to an increase in appetite.

Topics: Adiposity; Appetite; Body Composition; Body Mass Index; Child; Estradiol; Female; Ghrelin; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Leptin; Peptide YY; Puberty, Precocious

This study investigated the relationships of circulating leptin, kisspeptin, and neurokinin B (NKB) levels with precocious puberty (PP) in overweight/obese girls and evaluated the usefulness of these markers in the initiation of puberty. One hundred and twenty-eight girls aged 7.0-8.9 years with PP (group A, normal-weight; group B, overweight/obese) and 30 age-matched normal controls (NC) were enrolled. Serum levels of leptin, kisspeptin, and NKB were measured by commercial kits. Serum leptin levels were higher in group A (4.21 ng/mL) and B (5.64 ng/mL) compared to the NC (2.35 ng/mL, p < .001). Serum kisspeptin levels were lower in group A (0.59 ng/mL) than in group B (0.66 ng/mL, p = .018). Serum NKB levels were not different among the three groups. The predictive value of leptin (AUC =0.791) was lower than that of IGF-1 (AUC =0.917, p = .009), although both were significant markers for PP in the regression analysis. BMI z-score (AUC =0.806) was a predictive factor of PP. In conclusion, a higher level of leptin, IGF-1, and fatness in overweight/obese girls with PP compared to the NC confirms their roles in the regulation of puberty. Further research is needed if the effects of kisspeptin and NKB on puberty are limited at the levels of neurons or target tissue.

Topics: Biomarkers; Body Mass Index; Case-Control Studies; Child; Female; Humans; Kisspeptins; Leptin; Neurokinin B; Overweight; Pediatric Obesity; Predictive Value of Tests; Puberty, Precocious; Sexual Maturation

Background Adolescents having early puberty (EP) are more likely to have obesity and increased cardiometabolic and inflammatory markers and atherosclerosis risk. We aimed to assess the indirect and mediated effects of leptin and adiposity on the relation between EP and cardiometabolic and inflammatory markers in European adolescents. Methods A sample of 511 adolescents with EP (12.5-17.5 years) from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study was studied. To assess whether leptin levels and adiposity mediate the relation between EP and several biomarkers, linear regression models for mediation analyses were performed. Results EP was positively associated with the atherogenic index (Ath-I) (β=0.174; 95%CI 0.029-0.265) and negatively associated with the C-reactive protein (CRP) (β=-0.284; 95%CI -0.542 to -0.028) in girls. These associations were fully mediated by leptin levels (9.5%) and adiposity (44%), respectively. Moreover, EP has indirect effects on the apolipoprotein A-1 (ApoA-1) levels through adiposity in girls (for body mass index [BMI], β=0.014; 95%CI 0.005-0.028, and for waist circumference [WC], β=0.011; 95%CI 0.003-0.024), and on ApoA-1 (β=0.012; 95%CI 0.004-0.025), apolipoprotein B (ApoB) (β=-0.004; 95%CI -0.011 to -0.0004) and CRP (β=-0.265; 95%CI -0.819 to -0.047) through abdominal fat in boys. Conclusions Leptin levels and adiposity seem to play an important indirect and mediation role in the association between EP and cardiometabolic and inflammatory markers in adolescents. Weight control should be recommended in order to control the impaired cardiometabolic and inflammatory status arising in early pubertal adolescents.

Topics: Adiposity; Adolescent; Apolipoprotein A-I; Biomarkers; Body Mass Index; C-Reactive Protein; Child; Cross-Sectional Studies; Europe; Female; Humans; Leptin; Male; Puberty; Puberty, Precocious; Waist Circumference

The aim of the present study was to compare serum leptin, kisspeptin, total adiponectin, high molecular weight (HMW) adiponectin and neuropeptide Y (NPY) levels between girls with central precocious puberty (CPP; n=26, 7-9.5 years old) and age-matched controls (n=29) including or excluding obese girls. Leptin and NPY levels were comparable between CPP and control girls. Kisspeptin levels were lower in the CPP than control group, and were positively correlated with oestrogen in the control group and with systolic and diastolic blood pressure in the CPP group. Kisspeptin levels were negatively correlated with FSH and LH in the CPP group. Total adiponectin levels were lower in CPP than control girls, and were negatively correlated with Tanner stage and body mass index, but positively correlated with the quantitative insulin sensitivity check index in the control group. HMW adiponectin was higher in the CPP than control group, and was positively correlated with Tanner stage and LH in all girls. Total adiponectin had a strong positive correlation with HMW adiponectin in the CPP group (r=0.915) compared with the control group (r=0.371). In conclusion, kisspeptin may be associated with increased oestrogen in prepubertal girls, but with increased blood pressure in girls with CPP. In girls entering puberty, HMW adiponectin was increased and associated with reproductive parameters. Based on these observations, HMW adiponectin probably plays an essential role in the initiation of puberty and is a candidate marker for the prediction of CPP.

Topics: Adiponectin; Biomarkers; Case-Control Studies; Child; Female; Humans; Kisspeptins; Leptin; Molecular Weight; Neuropeptide Y; Puberty, Precocious

Patients with central precocious puberty (CPP) may have increased serum leptin levels; however, it is not well known whether this increase differs between patients with and without obesity. Our objectives were to describe the changes in serum leptin in girls with CPP in the first 12 months after diagnosis based on body mass index (BMI) and to explore whether serum leptin level at CPP diagnosis is related to BMI z-score (BMIz) after a 1-year follow-up.. A prospective cohort study was performed. We included 42 girls with idiopathic CPP in Tanner stages II and III. Anthropometric measurements were performed, and serum leptin was measured at study initiation and after 12 months. Patients were stratified according to BMI category (30 with a BMI in the <94th percentile and 12 with a BMI in the >95th percentile). Study variables were compared. Correlations among leptin, BMIz, and body fat were assessed.. Leptin increased gradually during the first year of treatment. In girls with a BMI in the <94th percentile at diagnosis, body fat percentage increased gradually during the first year of follow-up.. Girls with a BMI in the <94th percentile have a greater risk of weight increase. Leptin level >10.5 ng/dL at diagnosis is a risk factor for weight gain after 1 year.. BMI = body mass index BMIz = BMI z-score CPP = central precocious puberty GnRHa = gonadotropin-releasing hormone analogue.

Topics: Body Mass Index; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Leptin; Pediatric Obesity; Puberty, Precocious; Weight Gain

Precocious puberty which impacts children physically and psychologically has become one of the health problem over the world. However, the mechanism and preventive measures of precocious puberty is still not clear. Recent studies suggested that leptin may act as the 'permissive factor' to initiate the puberty by regulating gonadotrophin-releasing hormone secretion. Previous evidence from animal and human studies found that tea polyphenols can reduce serum leptin levels in vivo and inhibit the expression of leptin in adipose tissue. This article focus on whether tea polyphenols could delay the onset of puberty by reducing leptin levels. To verify the possibility of tea polyphenols on preventing precocious puberty, animal experiment can be used. Our hypothesis that tea polyphenols could prevent the precocious puberty may provide important potential way for the prevention and control of children precocious puberty.

Topics: Animals; Female; Gonadotropin-Releasing Hormone; Humans; Leptin; Luteinizing Hormone; Male; Mice; Polyphenols; Puberty, Precocious; Rats; Rats, Sprague-Dawley; Sexual Maturation; Tea; Vagina

The aim of the present study was to investigate the diagnostic role of serum neurokinin B level and its relationship with kisspeptin and leptin, which are known to be involved in the initiation of pubertal process. Girls who presented with breast development (<8 years) were included in the study. All patients underwent bone age assessment. Basal levels of serum follicle stimulating hormone and luteinizing hormone were measured and gonadotropin releasing hormone stimulation test was performed. Patients with a bone age/chronological age ratio >1 and a peak luteinizing hormone response in gonadotropin releasing hormone stimulation test >5mIU/L were included in the central precocious puberty group, while patients who did not meet these criteria were included in the premature thelarche group. Patients with organic pathologies were excluded. Healthy prepubertal girls with similar age were included as the control group. Leptin, kisspeptin and neurokinin B levels were measured by ELISA method. The study included 20 girls with idiopathic central precocious puberty 22 girls with premature thelarche and 24 prepubertal controls. While serum kisspeptin, leptin and neurokinin B levels were significantly higher in central precocious puberty and premature thelarche groups compared to controls, no significant difference was found between central precocious puberty and premature thelarche groups. Increased serum levels of leptin, kisspeptin and neurokinin B in patients with premature thelarche and central precocious puberty suggest that they take part during the initiation of pubertal process, however, these markers are not able to differentiate patients with central precocious puberty from premature thelarche.

Topics: Biomarkers; Child; Child, Preschool; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Female; Humans; Kisspeptins; Leptin; Neurokinin B; Puberty, Precocious

We aimed to investigate serum nesfatin-1 level in girls with premature thelarche (PT) and its relationship with anthropometric parameters and leptin, which are involved in the initiation of pubertal process.. Non-obese girls who presented with the complaint of early (2-8 years) and isolated breast development were included in the study. The control group consisted of age-matched healthy prepubertal girls. Auxological measurements were performed in all subjects. Gonadotropin-releasing hormone (GnRH) stimulation test and bone age assessment were conducted in subjects with early breast development. Girls with a bone age/chronologic age ratio <1.2 and a peak luteinizing hormone (LH) response to GnRH stimulation <5 mIU/L were included in the PT group.. The study included 22 non-obese girls with PT and 24 healthy prepubertal controls. Body mass index (BMI), BMI-standard deviation score (SDS) and height SDS were similar between the groups (p > 0.05). Serum leptin and nesfatin-1 levels were found significantly higher in the PT group compared to controls (p < 0.05). No correlation was detected between nesfatin-1 and basal LH, basal follicle stimulating hormone (FSH), stimulated peak LH, peak FSH, leptin levels and anthropometric parameters in the PT group (p > 0.05).. Results of the present study showed that serum nesfatin-1 and leptin levels are significantly higher in girls with PT than in prepubertal controls. This finding suggests that similar to leptin, nesfatin-1 may also have a central or peripheral role in the initiation of pubertal process and may be related to PT pathogenesis.

Topics: Biomarkers; Calcium-Binding Proteins; Child; Child, Preschool; DNA-Binding Proteins; Female; Humans; Leptin; Nerve Tissue Proteins; Nucleobindins; Obesity; Puberty, Precocious

To explore the effects of obesity on the peak level of luteinizing hormone (LH) in the gonadotropin-releasing hormone (GnRH) agonist test and obesity-related hormones in girls with central precocious puberty (CPP).. Three hundred and thirty-three girls with CPP who underwent the GnRH agonist test between 2012 and 2014 were classified into three groups: normal weight (n=123), overweight (n=108), and obesity (n=102), according to body mass index (BMI). The sexual development indices were compared between the three groups. Twenty girls were randomly selected from each group for evaluation of the serum levels of leptin, sex hormone binding globulin (SHBG), neurokinin B, and kisspeptin. The correlation of BMI with the levels of various hormones was assessed using Pearson correlation analysis.. There was no significant difference in mean age at diagnosis between the three groups; however, the bone age was significantly higher in the overweight and obesity groups than in the normal weight group (P<0.05). The peak level of LH in the GnRH agonist test and SHBG level in the normal weight group were significantly higher than those in the overweight and the obesity groups, while the serum levels of leptin and neurokinin B were significantly lower in the normal weight group than in the overweight and the obesity groups (P<0.05). BMI was negatively correlated with the peak level of LH in the GnRH agonist test and SHBG level (P<0.05), and positively correlated with the levels of leptin and neurokinin B (P<0.05).. The effects of BMI on the result of the GnRH agonist test and levels of obesity-related hormones should be taken into account in girls with precocious puberty.

Topics: Body Mass Index; Child; Female; Gonadotropin-Releasing Hormone; Humans; Leptin; Luteinizing Hormone; Neurokinin B; Obesity; Puberty, Precocious; Sex Hormone-Binding Globulin

It has been reported that leptin receptors have been also shown in mammary epithelial cells, and it has been suggested that leptin is involved in the control of the proliferation of both normal and malignant breast cells. The aim of this study was to measure the leptin levels in girls with early breast development and to determine if leptin levels were associated with the clinic, anthropometric characteristics and other sex steroids in girls with premature thelarche (PT).. In this cross-sectional study; we examined 26 girls (mean age, 7.1 ± 0.8 years; and mean body mass index standard deviation score [BMI-SDS], 0.45 ± 0.9) referred for evaluation because of the appearance of breast buds before the age of 8 years and judged clinically to have PT, as well as 21 healthy age-matched prepubertal girls who served as controls. Breasts and pubic hair development were assessed by visual inspection and palpation using the rating scales of Tanner.. There were significant differences between the PT and control groups regarding leptin (2.7 ± 2.4 vs 1.1 ± 1.1 ng/mL; P: 0.007) and androstenedione (0.44 ± 0.2 vs 0.29 ± 1.1 ng/mL; P = 0.019) levels despite their similar age and BMI-SDS. Leptin measurements were positively correlated with BMI-SDS (r = 0.378; P = 0.03) and androstenedione (r = 0.438; P = 0.025) levels.. Our study demonstrated that serum leptin levels were consistently higher in children with PT than in healthy children. Our findings also support an association between increased leptin levels in PT and adrenal androgens such as androstenedione. We suggest that the increased adrenal androstenedione, observed in our patients, may serve as a precursor for the peripheral conversion to estrogens by the stimulating effect of leptin on aromatase enzyme activity in breast tissues.

Topics: Biomarkers; Body Mass Index; Breast; Child; Cross-Sectional Studies; Female; Humans; Leptin; Puberty, Precocious

Three single-nucleotide polymorphisms (SNPs) in the leptin (LEP) or leptin receptor (LEPR) genes were assessed for their association with central precocious puberty (CPP).. The control group with the A/G SNP at LEPR 223 or A/G SNP at LEPR 109 exhibited significantly higher peak luteinizing hormone (LH) levels. The leptin level in the CPP group was significantly higher than that in the control group, but SNPs in either LEP or LEPR gene could not explain this observation.. In conclusion, SNPs at LEPR 223 and LEPR 109 were significantly associated with higher levels of LH in girls without CPP, but none of the genotypes at these SNPs were significantly associated with CPP.. The SNP genotypes of LEP (polymorphism at promoter at nt-2548) and LEPR (223A/G, 109A/G) of 219 healthy girls and 249 girls diagnosed with CPP were compared. Allele frequencies in SNPs were compared with anthropometric measures, circulating leptin, hormones (estradiol, follicle-stimulating hormone, and LH), and lipid concentrations for CPP risk.

Topics: Alleles; Anthropometry; Case-Control Studies; Child; Estradiol; Female; Follicle Stimulating Hormone; Gene Frequency; Genotype; Humans; Leptin; Luteinizing Hormone; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Puberty, Precocious; Receptors, Leptin; Risk

The system KISS1-KISS1R is one of the main regulators of the hypothalamic-pituitary-gonadal axis and constitutes a link between metabolism and reproduction through its interaction with leptin. The aim of this study was to clarify the possible utility of kisspeptin as a pubertal marker and/or the possible influence of nutritional status in kisspeptin levels. To this end, we have studied kisspeptin plasma levels throughout sexual development and in prepubertal obese girls and girls affected by idiopathic central precocious puberty (CPP). Plasma kisspeptin concentrations were analyzed by RIA. An increase in kisspeptin levels was observed in adult females compared to healthy prepubertal and pubertal girls (p<0.001) and to adult males (p<0.001). Additionally, kisspeptin was increased in prepubertal obese girls compared to healthy prepubertal girls (p<0.01) and girls with idiopathic CPP (p<0.05). As revealed by the regression analysis, in prepubertal healthy and obese girls and girls with idiopathic CCP, the parameters that influenced kisspeptin levels were BMI (R(2)=0.10, p<0.05) and leptin levels (R(2)=0.14, p<0.01). In conclusion, kisspeptin levels do not seem to be a good pubertal marker. The results obtained in prepubertal and idiopathic CCP girls point to a relationship between leptin, BMI and kisspeptin at least in this group, and suggest a possible role for adipose tissue in the modulation kisspeptin synthesis.

Topics: Adolescent; Adult; Biomarkers; Body Mass Index; Case-Control Studies; Child; Cross-Sectional Studies; Female; Humans; Kisspeptins; Leptin; Male; Obesity; Puberty; Puberty, Precocious; Regression Analysis; Young Adult

Premature thelarche in later childhood may progress to central precocious puberty (CPP), which does not spontaneously resolve. Thelarche variant (TV) is a slowly progressive variant of precocious puberty.. To determine and compare levels of insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3) and anthropomorphic measures in girls with TV and CPP.. Prepubertal controls and girls with TV and CPP.. Chronological and bone age, weight, height, BMI, height velocity (HV), and serum IGF-I, IGFBP-3, leptin, follicle-stimulating hormone (FSH) and lutenizing hormone (LH) levels were assessed.. Serum IGF-I levels, HV and IGF-I/ IGFBP-3 ratio were significantly higher in girls with CPP compared to both controls and girls with TV. IGFBP-3 values for bone age (IGFBP-3BA) were significantly higher in the TV group compared to both controls and girls with CPP. FSH and LH concentrations were significantly higher in the CPP group compared to TV.. HV, IGF-I, LH and FSH levels and IGF-I/IGFBP-3 ratio are elevated in girls with CPP compared to those with TV.

Topics: Age Determination by Skeleton; Anthropometry; Body Height; Body Weight; Breast; Child; Female; Follicle Stimulating Hormone; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Luteinizing Hormone; Puberty, Precocious

Girls with premature adrenarche (PA) are at risk for multiple problems related to exaggerated androgen synthesis. Whether PA carries a risk of psychopathology remains unknown. This study examined group differences in: (a) anthropometric and endocrine parameters, and (b) mood and behavior problems, in 6-8 year-old girls with PA (n = 40) compared to on-time adrenarche girls (n = 36). PA girls were taller (p < or =0.05) and heavier (p < or =0.01) than the on-time adrenarche girls but body mass index showed no difference. PA girls had significantly (p <0.05) higher adrenal androgen and testosterone concentrations but not cortisol or leptin. PA girls also had significantly more oppositional defiant disorder, and higher symptom counts reflecting anxiety, mood or disruptive behavior disorders. PA girls may be more vulnerable to psychopathology than on-time adrenarche girls. The challenge of future studies is to determine which PA girls are at risk for psychopathology and which are more resilient.

Topics: Adrenarche; Affect; Androgens; Anxiety; Body Height; Body Weight; Case-Control Studies; Child; Female; Humans; Hydrocortisone; Leptin; Puberty, Precocious; Testosterone

Menarche is a milestone of reproductive development, and its timing may be differentially influenced by the growth conditions before birth and those between birth and puberty. The present study explored the relationships among menarcheal timing and markers of prenatal and midchildhood growth in healthy Australian girls.. A total of 156 girls aged 8 yr from a birth cohort of full-term babies had height, weight, and waist circumference measured. One hundred three girls had dual x-ray absorptiometry performed and blood analyzed for insulin, leptin, IGF-I, estradiol, and dehydroepiandrosterone sulfate levels. Girls were followed up at age 15 yr and their age of menarche was recorded.. Measures included age of menarche; birth weight and birth length; height, weight, waist circumference, and body composition by dual x-ray absorptiometry; and plasma insulin, leptin, IGF-I, estradiol, and dehydroepiandrosterone sulfate at age 8 yr.. Girls with earlier menarche were light and long at birth and had higher total and central adiposity and IGF-I and estradiol levels in midchildhood, compared with those with later menarche. Age of menarche was best predicted by combining size at birth and body mass index z score at age 8 yr (r2 = 0.12; P < 0.001).. The timing of menarche appears to be influenced in opposing directions by pre- and postnatal growth. Menarche was found to occur earlier in girls who were long and light at birth and who had a higher fat mass and circulating IGF-I in childhood. These findings may partly explain ethnic differences and secular trends in the age of menarche.

Topics: Adolescent; Birth Weight; Body Fat Distribution; Body Height; Body Mass Index; Body Size; Body Weight; Child; Estradiol; Female; Fetal Development; Follow-Up Studies; Humans; Infant, Newborn; Insulin; Insulin-Like Growth Factor I; Leptin; Menarche; Puberty, Delayed; Puberty, Precocious; Regression Analysis

Polycystic ovary syndrome is considered to originate during puberty. The aim of this study was to investigate hormonal status in relationship to anthropometric data in girls with premature adrenarche and adolescent girls with hyperandrogenism, as these conditions are related to polycystic ovary syndrome in adulthood.. 20 girls with premature adrenarche (aged 4.9-10.2 years), 21 postmenarcheal girls with hirsutism (aged 13.3-17.8 years), 2 groups (n=13 in each) of healthy volunteers of similar age and body mass index participated in the study.. Serum testosterone and dehydroepiandrosterone sulphate levels were significantly higher in all patients than in controls. Free androgen index and leptin levels were significantly higher, and sex-hormone-binding globulin lower in hirsute adolescents vs. controls. Birth weight standard deviation scores were comparable in all 4 groups. Serum dehydroepiandrosterone sulphate negatively correlated with birth weight standard deviation scores in the group of girls with premature adrenarche (r=-0.57, p<0.001). By linear regression, 76% in variation of serum leptin levels could be explained by subscapular skinfold thickness standard deviation scores, and by serum sex-hormone-binding globulin, insulin, and dehydroepiandrosterone sulphate levels in all participants. Mean age of onset of menarche was younger in hirsute girls vs. controls (12.1+/-1.3 vs. 13.5+/-1.3 years, p=0.004).. Inverse correlation of dehydroepiandrosterone sulphate levels and weight at birth indicates relationship between premature adrenarche in girls and fetal growth. Higher leptin levels in adolescents with hyperandrogenism than in healthy girls show possible involvement of leptin in pathogenesis of hyperandrogenism.

Topics: Adolescent; Age Factors; Birth Weight; Body Height; Body Mass Index; Body Weight; Child; Child, Preschool; Dehydroepiandrosterone Sulfate; Female; Hirsutism; Humans; Hyperandrogenism; Insulin; Leptin; Linear Models; Menarche; Polycystic Ovary Syndrome; Puberty, Precocious; Risk Factors; Testosterone

A transient increase in height and bone age as well as hyperinsulinism is seen in patients with premature adrenarche (PA). In addition, the weights of these patients are more than those of healthy peers. The aim of this study was to evaluate the role of leptin, IGF-I and IGFBPs in hyperandrogenemia and increased body weight observed in girls with PA. In this study, IGF-I, IGFBP-3, IGFBP-1 and leptin levels were investigated in 27 children with PA aged 5.4-8.6 years and 13 healthy children aged 5.7-8.58 years. Twenty patients were lean. The bone ages and BMIs of the children with PA were significantly higher than those of the healthy controls (p < 0.05). IGF-I (p < 0.005), IGFBP-3 (p < 0.05) and leptin (p < 0.0001) levels of lean PA girls were higher than controls. The leptin level of the obese PA girls was higher than that of the lean PA girls (p < 0.05) and controls (p < 0.0001). The IGFBP-1 level of the PA girls with and without obesity was lower than controls (p < 0.05). A negative correlation was observed between IGFBP-1 and leptin levels of the girls with PA (r = -0.64, p < 0.05). Serum leptin levels were influenced by BMI (p = 0.001), basal 17-OHP (p = 0.002) and stimulated 17-OHP (p = 0.019) in patients with PA. In conclusion, we suggest that elevated IGF-I and insulin give rise to increased adrenal androgens and leptin levels. On the other hand, both insulin and leptin cause decreased levels of IGFBP-1 in girls with PA, even if they are lean.

Topics: Body Mass Index; Bone Development; Case-Control Studies; Child; Child, Preschool; Female; Humans; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Leptin; Obesity; Puberty, Precocious

Few data are available regarding leptin levels in children with different pubertal stages or with precocious puberty (PP). The aim of this study was to assess the changes in serum leptin levels in patients with PP. We studied 20 girls with PP, with Tanner stage II-III; the age at the beginning of pubertal signs ranged from 4.2 to 7.1 yr; all the girls had an advantaged bone age. Controls were subdivided in two groups: group 1: 20 pre-pubertal girls with the same chronological age of the patients, without any signs of pubertal development (Tanner stage I); group 2: 20 additional girls with the same bone age, pubertal stage and body mass index (BMI) of the girls with PP. Serum leptin levels in females with PP are similar to those found in subjects with normal puberty (9.0 +/- 0.8 vs 9.1 +/- 0.9 ng/ml; ns) and different from subjects with the same chronological age without activation of puberty (5.6 +/- 0.9 ng/ml, p < 0.001). In all groups leptin levels correlated significantly with BMI (girls with PP: r = 0.5 1, p < 0.02; control group 1 girls: r = 0.71; p < 0.0001; control group 2 girls: r = 0.49; p < 0.02), there was no significant relationship between leptin and activation of hypothalamic-pituitary-gonadal axis. Our results indicate that the serum leptin levels in the girls with PP are not significantly different from levels in healthy girls at a similar stage of pubertal development, suggesting that the relationship between serum leptin levels and BMI is also present in this pathological situation.

Topics: Age Determination by Skeleton; Body Composition; Body Mass Index; Case-Control Studies; Child; Female; Humans; Leptin; Puberty; Puberty, Precocious

Previous studies have examined the relationship between leptin, body mass, and pubertal status. The present study directly compares the relationship of leptin and estradiol in 5 groups of girls with different combinations of pubertal status and weight.. We studied girls with idiopathic precocious puberty, age-matched non-obese prepubertal girls, age-matched obese prepubertal girls, normal pubertal girls, and obese pubertal girls (n=12/group).. Leptin levels were significantly higher in obese pubertal girls (26.6+/-8.4 ng/mL) than in all others. Leptin levels were significantly higher in obese prepubertal girls (20.7+/-10.9 ng/mL) (mean+/-SD) compared to girls with precocious puberty (7.7+/-5.4 ng/mL, p<0.004), non-obese prepubertal girls (5.55+/-3.6 ng/mL, p<0.001), and normal pubertal girls (4.8+/-2.9 ng/mL, p<0.001). Leptin level did not correlate significantly with estradiol level. Leptin-SDS (standard deviation score), which corrects leptin level for gender, pubertal stage, and BMI, was significantly lower in the obese pubertal group than in the 3 non-obese groups.. These findings confirm previous studies that body mass, chronological age and pubertal stage are determinants of leptin level. However, these are not the only factors determining leptin level as evidenced by persistent differences in leptin level between obese and non-obese pubertal girls even when correcting for pubertal stage and BMI. While the present study provides no new answers to the question of pubertal regulation, it provides a direct comparison of combinations of weight, pubertal stage, and leptin level, as background for future studies.

Topics: Body Mass Index; Body Weight; Case-Control Studies; Child; Estradiol; Female; Humans; Leptin; Obesity; Puberty; Puberty, Precocious

Topics: Age of Onset; Child; Child, Preschool; Female; Humans; Hypothalamic Neoplasms; Hypothalamus; Incidence; Infant; Leptin; Luteinizing Hormone; Magnetic Resonance Imaging; Male; Puberty, Precocious; Risk Factors; Sex Factors; Tomography, X-Ray Computed

To determine whether the initial presentation of patients with central precocious puberty (CPP) varies according to the aetiology, whether this permits the differentiation between idiopathic and organic forms, and whether the body mass index (BMI) and plasma leptin concentrations are linked to gonadotrophin secretion.. The clinical and laboratory features of 256 patients (26 boys and 230 girls) with CPP were studied separately in boys and girls. We compared patients with idiopathic CPP (seven boys and 186 girls) to those with organic CPP, whose pubertal development revealed a central nervous system (CNS) lesion (five boys and 11 girls), and to patients with organic CPP associated with a previously treated CNS lesion (14 boys and 33 girls).. Boys with organic CPP, having revealed or treated CNS lesions, started their puberty earlier (3.0 +/- 1.0 years and 6.7 +/- 0.5 years) than boys with idiopathic CPP (8.5 +/- 0.2 years, P < 0.01 and < 0.05). Boys with organic CPP associated with a treated CNS lesion had lower luteinizing hormone (LH)/follicle stimulating hormone (FSH) peaks ratio after stimulation with gonadotrophin releasing hormone (GnRH) (1.6 +/- 0.5) than did boys with idiopathic CPP (2.2 +/- 0.3, P < 0.05). Girls with organic CPP revealing a CNS lesion started their puberty earlier (3.6 +/- 0.9 years) than girls with idiopathic CPP (6.6 +/- 0.1 years, P < 0.0 l) and had higher LH (P < 0.01) and FSH peaks (< 0.05). Girls with organic CPP associated with a treated CNS lesion had higher BMI (1.8 +/- 0.2 z-score) than did girls with idiopathic CPP (1.3 +/- 0.1 zs, P < 0.05), higher leptin concentrations (11.7 +/- 1.8 microg/l vs. 7.7 +/- 0.5 microg/l, P < 0.0 l), LH peak (P < 0.01), FSH peak (P < 0.05) and LH/FSH peaks ratio (1 +/- 0.1 vs. 0.8 +/- 0.1, P < 0.05). Only 12.4% of the girls with idiopathic CPP had BMI-zs < 0, and their plasma leptins were positively correlated with BMI (P < 0.0001).. The features of central precocious puberty vary according to the aetiology, but it is impossible to exclude a central nervous system lesion in a given patient with central precocious puberty without performing central nervous system imaging. This imaging remains necessary in all cases of central precocious puberty. Most of the girls with idiopathic central precocious puberty had increased BMI, but we found no correlation between plasma leptin concentrations and gonadotrophin secretion.

Topics: Age of Onset; Body Mass Index; Child; Child, Preschool; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hypothalamic Neoplasms; Leptin; Luteinizing Hormone; Male; Puberty, Precocious; Sex Factors; Testosterone

Hyperinsulinism and hyperandrogenism have the capacity to increase bone mineral density (BMD) and serum leptin, independently of body fat mass. We therefore assessed lumbar BMD and serum leptin in girls with the sequence of a low birthweight and precocious pubarche (PP) in childhood, in whom hyperinsulinism and hyperandrogenism have been described.. Fifty-two non-obese PP girls were studied (age range 6.9-14.9 years). Serum leptin was also measured in 42 control girls, matched for age, body mass index and pubertal stage.. BMD SDS, measured by dual-energy X-ray absorptiometry, was elevated in PP girls compared to the population reference (0.39 +/- 0.18 SDS; p = 0.03) and bone age, assessed from hand radiographs, was significantly advanced compared to chronological age (1.2 +/- 0.1 years; p < 0.0005).. Compared to control girls, PP girls had higher leptin levels for degree of body mass index (PP girls: 9.4 +/- 0.6 ng/ml; controls: 7.8 +/- 0.6 ng/ml; p = 0.01). In PP girls, serum leptin was inversely related to birthweight (r = -0.32, p = 0.01) and positively related to free androgen index (FAI) (r = 0.71, p < 0.0005). BMD SDS was also inversely related to birthweight (r = -0.26, p < 0.05) and positively related to serum leptin (r = 0.42, p < 0.05), FAI (r = 0.45, p < 0.05) and mean serum insulin during oral glucose tolerance testing (MSI) (r = 0.59, p < 0.0005). In multiple regression, MSI was the strongest determinant of BMD SDS (beta = 0.50, p = 0.002). In conclusion, elevated BMD and serum leptin in non-obese PP girls were related to degrees of low birthweight, hyperinsulinism and hyperandrogenism. The characteristic hyperinsulinism of PP girls is proposed to be the key variable in this constellation.

Topics: Adolescent; Age Determination by Skeleton; Androgens; Birth Weight; Body Mass Index; Bone Density; Child; Female; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Leptin; Puberty, Precocious; Reference Values

Serum leptin concentrations increase during childhood in both sexes. During sexual maturation, levels rise further in girls, but decrease in boys. These data suggest that testosterone either directly suppresses leptin levels or induces changes in body composition that result in lower leptin concentrations. To examine further the relationship between sex steroids and leptin, we performed a longitudinal study in children with central precocious puberty (28 girls and 12 boys) before, during, and after discontinuation of GnRH agonist-induced pituitary-gonadal suppression. Nighttime and daytime leptin levels were measured to determine whether the activity of the pituitary-gonadal axis affects their diurnal variation. In the boys, suppression of testosterone increased leptin levels, whereas resumption of puberty was associated with decreased leptin levels [3.5 +/- 0.8 vs. 9.5 +/- 3.1 ng/dL (P = 0.005) and 12.2 +/- 4.5 vs. 7.0 +/- 2.6 ng/dL (P = 0.012), respectively]. Serum leptin levels did not change in the girls with alteration of the pituitary-ovarian axis and consistently exceeded those in boys. Nighttime levels were consistently greater than daytime values by an average of 38.3% in the girls and 29.4% in the boys. These serial observations during reversible pituitary-gonadal suppression suggest that testosterone decreases leptin concentrations, but that estrogen, at least in this childhood model, has no discernible effect. In addition, our data indicate that the presence of the diurnal rhythm in leptin concentrations is independent of the state of the reproductive axis.

Topics: Adolescent; Child; Circadian Rhythm; Depression, Chemical; Estradiol; Female; Humans; Leptin; Male; Obesity; Proteins; Puberty, Precocious; Receptors, Leptin; Receptors, LHRH; Testosterone

Several studies have suggested that sufficient serum leptin levels may be involved in the initiation of puberty. To assess further the relationship between leptin and the onset of puberty in humans, we measured the serum leptin concentration in children with central precocious puberty (CPP). We studied 65 children with either idiopathic (IPP; n = 50 girls and 3 boys) or neurogenic central precocious puberty (NPP; n = 5 girls and 7 boys). The serum leptin levels in these patients were compared with normative data from healthy children and adolescents using SD scores that adjust for body mass index (BMI) and Tanner stage. The mean SD scores of IPP and NPP girls were +0.4 +/- 0.1 and +1.0 +/- 0.5, respectively, compared with that of age-matched prepubertal girls and +0.7 +/- 0.2 and +1.6 +/- 0.6 compared with that of girls matched for pubertal stage. The CPP girls with lower BMIs contributed larger SD scores, such that the leptin SD score was negatively correlated with BMI. A similar, modest increase in leptin levels in the CPP girls was evident when additional normative data were considered. The mean leptin SD scores of IPP and NPP boys were -0.9 +/- 0.5 and +0.7 +/- 0.3, respectively, compared with that of normal boys at Tanner stage 3-4. Serum leptin levels in the boys with CPP were not different from those in healthy boys in any of the normative studies. These data should be interpreted cautiously, but they suggest that girls with CPP have modestly elevated serum leptin concentrations compared with those in healthy children and adolescents. In addition, the negative correlation between the leptin SD score and BMI suggests that sufficient leptin levels may be associated with initiation of puberty in girls.

Topics: Body Mass Index; Case-Control Studies; Child; Female; Humans; Hypothalamo-Hypophyseal System; Leptin; Linear Models; Male; Obesity; Proteins; Puberty, Precocious; Signal Transduction