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European Journal of Endocrinology Mar 2020Pregnancy-associated plasma protein-A2 (PAPP-A2) is a metalloproteinase that cleaves IGFBP-3 and IGFBP-5. Human mutations in PAPPA2 result in short stature with a low...
OBJECTIVE
Pregnancy-associated plasma protein-A2 (PAPP-A2) is a metalloproteinase that cleaves IGFBP-3 and IGFBP-5. Human mutations in PAPPA2 result in short stature with a low percentage of free IGF-I. Little is known about PAPP-A2 levels and the regulation of free IGF-I throughout childhood. We examined PAPP-A2 and intact IGFBP-3 levels in childhood and explored associations between PAPP-A2, free and total IGF-I, and total and intact IGFBP-3 and their relationship to the percentage of free to total IGF-I and anthropometric factors.
DESIGN
Cross-sectional study at a single center.
METHODS
PAPP-A2, free IGF-I, and intact IGFBP-3 levels were measured in childhood (3-18 years old) and an evaluation of the relationship between these proteins and anthropometric factors.
RESULTS
In 838 children, PAPP-A2 consistently decreased throughout childhood. In contrast, free IGF-I increased. A pubertal peak in free IGF-I was present in females but was less evident in males. Intact and total IGFBP-3 increased throughout childhood; however, intact IGFBP-3 had a more marked rise than total IGFBP-3. Percent free IGF-I decreased with no distinct pubertal peak. PAPP-A2 levels positively correlated with the percent free IGF-I (Male, Female; r = 0.18, 0.38; P < 0.001) and negatively with intact IGFBP-3 (Male, Female; r = -0.58, -0.65; P < 0.0001).
CONCLUSIONS
This is the first study to describe serum PAPP-A2 and intact IGFBP-3 in children between 3 and 18 years of age. Our correlative findings suggest that PAPP-A2 is an important regulator of the percent free IGF-I which can be a marker of perturbations in the GH/IGF-I axis.
Topics: Adolescent; Adolescent Development; Anthropometry; Body Height; Body Weight; Child; Child Development; Child, Preschool; Female; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Male; Pregnancy-Associated Plasma Protein-A; Puberty; Reference Values
PubMed: 31961798
DOI: 10.1530/EJE-19-0859 -
Jornal de Pediatria 2022Endocrine disrupting chemicals (EDCs) are present in many areas and materials of the common life, and exposure to these chemicals can occur from products to personal... (Review)
Review
OBJECTIVE
Endocrine disrupting chemicals (EDCs) are present in many areas and materials of the common life, and exposure to these chemicals can occur from products to personal care, from air and food. This review aims to summarize the more recent epidemiological findings for the impact of EDCs on endocrine system health in children, including effects in growth, metabolism, sexual development, and reproduction.
SOURCES
The MEDLINE database (PubMed) was searched on August 24th, 2021, filtering for EDCs, endocrine disruptors, children, and humans.
SUMMARY OF THE FINDINGS
Intrauterine exposure of EDCs can have transgenerational effects, thus laying the foundation for disease in later life. The dose-response relationship may not always be predictable as even low-level exposures that may occur in everyday life can have significant effects on a susceptible individual. Although individual compounds have been studied in detail, the effects of a combination of these chemicals are yet to be studied to understand the real-life situation where human beings are exposed to a "cocktail effect" of these EDCs. Epidemiological studies in humans suggest EDCs' effects on prenatal growth, thyroid function, glucose metabolism, obesity, puberty, and fertility mainly through epigenetic mechanisms.
CONCLUSIONS
EDCs cause adverse effects in animals, and their effects on human health are now known and irrefutable. Because people are typically exposed to multiple endocrine disruptors, assessing public health effects is difficult. Legislation to ban EDCs and protect especially pregnant women and young children is required and needs to be revised and adjusted to new developments on a regular basis.
Topics: Animals; Child, Preschool; Endocrine Disruptors; Epigenesis, Genetic; Female; Humans; Obesity; Pregnancy; Puberty
PubMed: 34921754
DOI: 10.1016/j.jped.2021.11.003 -
Fertility and Sterility Nov 2022To study whether the timing of puberty in adolescents who reported gender incongruence (incongruence between birth-assigned sex and self-identified gender) was different...
OBJECTIVE
To study whether the timing of puberty in adolescents who reported gender incongruence (incongruence between birth-assigned sex and self-identified gender) was different from those adolescents who reported gender congruence.
DESIGN
Population-based cohort study using data from the Danish National Birth Cohort.
SETTING
Not applicable.
PATIENT(S)
Birth-assigned boys and girls born between 2000 and 2003, who self-reported gender incongruence at 11 years (N = 10,046) and their pubertal developmental stages from age 11 years to every 6 months throughout puberty were included.
INTERVENTION(S)
Not applicable.
MAIN OUTCOME MEASURE
Mean age differences in months at reaching Tanner stages 2-5 for breast or genital development and pubic hair, voice break, first ejaculation, menarche, axillary hair, acne, and the average difference at attaining all pubertal milestones (primary outcome).
RESULT(S)
In total, 549 (5.5% ) adolescents reported part or full gender incongruence at 11 years. Tendencies toward earlier timing of puberty were observed in adolescents who reported part gender incongruence (average difference, birth-assigned boys: -3.2 months [95% confidence interval {CI}: -6.7; 0.3]; birth-assigned girls: -2.0 months [95% CI: -3.9; -0.1]). Tendencies toward earlier timing of puberty were observed in adolescents who reported full gender incongruence (average difference, birth-assigned boys: -2.4 months [95% CI: -5.0; 0.4]; birth-assigned girls: -1.9 months [95% CI: -5.1; 1.2]).
CONCLUSIONS
The results from this study indicated that birth-assigned boys and girls who reported either part or full gender incongruence tended to reach puberty slightly earlier than those adolescents who reported gender congruence at 11 years of age. Knowledge on the timing of puberty among adolescents who experience gender incongruence is essential to inform mutual decision-making in clinical settings.
Topics: Adolescent; Male; Female; Humans; Child; Cohort Studies; Puberty; Menarche
PubMed: 36163086
DOI: 10.1016/j.fertnstert.2022.07.018 -
Developmental Cognitive Neuroscience Dec 2022Adolescence is defined by puberty and represents a period characterized by neural circuitry maturation (e.g., fronto-striatal systems) facilitating cognitive...
Adolescence is defined by puberty and represents a period characterized by neural circuitry maturation (e.g., fronto-striatal systems) facilitating cognitive improvements. Though studies have characterized age-related changes, the extent to which puberty influences maturation of fronto-striatal networks is less known. Here, we combine two longitudinal datasets to characterize the role of puberty in the development of fronto-striatal resting-state functional connectivity (rsFC) and its relationship to inhibitory control in 106 10-18-year-olds. Beyond age effects, we found that puberty was related to decreases in rsFC between the caudate and the anterior vmPFC, rostral and ventral ACC, and v/dlPFC, as well as with rsFC increases between the dlPFC and nucleus accumbens (NAcc) across males and females. Stronger caudate rsFC with the dlPFC and vlPFC during early puberty was associated with worse inhibitory control and slower correct responses, respectively, whereas by late puberty, stronger vlPFC rsFC with the dorsal striatum was associated with faster correct responses. Taken together, our findings suggest that certain fronto-striatal connections are associated with pubertal maturation beyond age effects, which, in turn are related to inhibitory control. We discuss implications of puberty-related fronto-striatal maturation to further our understanding of pubertal effects related to adolescent cognitive and affective neurodevelopment.
Topics: Adolescent; Male; Female; Humans; Adolescent Development; Magnetic Resonance Imaging; Corpus Striatum; Puberty; Nucleus Accumbens
PubMed: 36495791
DOI: 10.1016/j.dcn.2022.101183 -
Puberty Timing and Sex-Specific Trajectories of Systolic Blood Pressure: a Prospective Cohort Study.Hypertension (Dallas, Tex. : 1979) Aug 2022Sex differences in systolic blood pressure (SBP) emerge during adolescence but the role of puberty is not well understood. We examined sex-specific changes in SBP...
BACKGROUND
Sex differences in systolic blood pressure (SBP) emerge during adolescence but the role of puberty is not well understood. We examined sex-specific changes in SBP preceding and following puberty and examined the impact of puberty timing on SBP trajectories in females and males.
METHODS
Trajectories of SBP before and after puberty and by timing of puberty in females and males in a contemporary birth cohort study were analyzed. Repeated measures of height from age 5 to 20 years were used to identify puberty timing (age at peak height velocity). SBP was measured on ten occasions from 3 to 24 years (N participants, 4062; repeated SBP measures, 29 172). Analyses were performed using linear spline multilevel models based on time before and after puberty and were adjusted for parental factors and early childhood factors.
RESULTS
Mean age at peak height velocity was 11.7 years (SD, 0.8) for females and 13.6 years (SD, 0.9) for males. Males had faster rates of increase in SBP before puberty leading to 10.19 mm Hg (95% CI, 6.80-13.57) higher mean SBP at puberty which remained similar at 24 years (mean difference, 11.43 mm Hg [95% CI, 7.22-15.63]). Puberty timing was associated with small transient differences in SBP trajectories postpuberty in both sexes and small differences at 24 years in females only.
CONCLUSIONS
A large proportion of the higher SBP observed in males compared with females in early adulthood is accrued before puberty. Interventions targeting puberty timing are unlikely to influence SBP in early adulthood.
Topics: Adolescent; Adult; Blood Pressure; Body Height; Child; Child, Preschool; Cohort Studies; Female; Humans; Male; Prospective Studies; Puberty; Risk Factors; Young Adult
PubMed: 35587023
DOI: 10.1161/HYPERTENSIONAHA.121.18531 -
Indian Pediatrics Nov 2023Linear growth, onset of and progress through puberty are all adversely affected by chronic diseases during childhood and adolescence. Peak bone mass accrual by the end...
Linear growth, onset of and progress through puberty are all adversely affected by chronic diseases during childhood and adolescence. Peak bone mass accrual by the end of adolescence determines adult fracture risk. Given that half of total lifetime bone mass is accrued during the pubertal years under the influence of sex hormones, normal timing of pubertal onset, with attention to completion of feminization for girls or virilization in boys is integral to achievement of optimal bone mass, which in turn will reduce adult fracture risk for those who have a chronic relapsing, remitting or persistent illness.
Topics: Male; Adult; Adolescent; Female; Humans; Bone Density; Bone and Bones; Puberty; Chronic Disease; Recurrence
PubMed: 37260064
DOI: No ID Found -
The Journal of Clinical Endocrinology... Nov 2023The melanocortin 3 receptor (MC3R) has recently emerged as a critical regulator of pubertal timing, linear growth, and the acquisition of lean mass in humans and mice....
CONTEXT
The melanocortin 3 receptor (MC3R) has recently emerged as a critical regulator of pubertal timing, linear growth, and the acquisition of lean mass in humans and mice. In population-based studies, heterozygous carriers of deleterious variants in MC3R report a later onset of puberty than noncarriers. However, the frequency of such variants in patients who present with clinical disorders of pubertal development is currently unknown.
OBJECTIVE
This work aimed to determine whether deleterious MC3R variants are more frequently found in patients clinically presenting with constitutional delay of growth and puberty (CDGP) or normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
METHODS
We examined the sequence of MC3R in 362 adolescents with a clinical diagnosis of CDGP and 657 patients with nIHH, experimentally characterized the signaling properties of all nonsynonymous variants found and compared their frequency to that in 5774 controls from a population-based cohort. Additionally, we established the relative frequency of predicted deleterious variants in individuals with self-reported delayed vs normally timed menarche/voice-breaking in the UK Biobank cohort.
RESULTS
MC3R loss-of-function variants were infrequent but overrepresented in patients with CDGP (8/362 [2.2%]; OR = 4.17; P = .001). There was no strong evidence of overrepresentation in patients with nIHH (4/657 [0.6%]; OR = 1.15; P = .779). In 246 328 women from the UK Biobank, predicted deleterious variants were more frequently found in those self-reporting delayed (aged ≥16 years) vs normal age at menarche (OR = 1.66; P = 3.90E-07).
CONCLUSION
We have found evidence that functionally damaging variants in MC3R are overrepresented in individuals with CDGP but are not a common cause of this phenotype.
Topics: Adolescent; Humans; Female; Animals; Mice; Receptor, Melanocortin, Type 3; Prevalence; Hypogonadism; Puberty, Delayed; Puberty; Growth Disorders
PubMed: 37339320
DOI: 10.1210/clinem/dgad373 -
American Journal of Medical Genetics.... Jun 2020Klinefelter syndrome is highly underdiagnosed and diagnosis is often delayed. With the introduction of non-invasive prenatal screening, the diagnostic pattern will... (Review)
Review
Klinefelter syndrome is highly underdiagnosed and diagnosis is often delayed. With the introduction of non-invasive prenatal screening, the diagnostic pattern will require an updated description of the clinical and biochemical presentation of infants with Klinefelter syndrome. In the first months of life, the hypothalamic-pituitary-gonadal (HPG)-axis is transiently activated in healthy males during the so-called minipuberty. This period represents a "window of opportunity" for evaluation of the HPG-axis before puberty and without stimulation tests. Infants with Klinefelter syndrome present with a hormonal surge during the minipuberty. However, only a limited number of studies exist, and the results are contradictory. Further studies are needed to clarify whether infants with Klinefelter syndrome present with impaired testosterone production during the minipuberty. The aim of this review is to describe the clinical and biochemical characteristics of the neonate and infant with Klinefelter syndrome with special focus on the minipuberty and to update the clinical recommendations for Klinefelter syndrome during infancy.
Topics: Humans; Hypothalamo-Hypophyseal System; Infant, Newborn; Klinefelter Syndrome; Male; Noninvasive Prenatal Testing; Puberty
PubMed: 32476267
DOI: 10.1002/ajmg.c.31794 -
Frontiers in Endocrinology 2022Bone age (BA) is a clinical marker of bone maturation which indicates the developmental stage of endochondral ossification at the epiphysis and the growth plate.... (Review)
Review
Bone age (BA) is a clinical marker of bone maturation which indicates the developmental stage of endochondral ossification at the epiphysis and the growth plate. Hormones that promote the endochondral ossification process include growth hormone, insulin-like growth factor-1, thyroid hormone, estrogens, and androgens. In particular, estrogens are essential for growth plate fusion and closure in both sexes. Bone maturation in female children is more advanced than in male children of all ages. The promotion of bone maturation seen in females before the onset of puberty is thought to be an effect of estrogen because estrogen levels are higher in females than in males before puberty. Sex hormones are essential for bone maturation during puberty. Since females have their pubertal onset about two years earlier than males, bone maturation in females is more advanced than in males during puberty. In the present study, we aimed to review the factors affecting prepubertal and pubertal BA progression, BA progression in children with hypogonadism, and bone maturation and deformities in children with Turner syndrome.
Topics: Bone Development; Child; Estrogens; Female; Human Growth Hormone; Humans; Male; Puberty
PubMed: 36072933
DOI: 10.3389/fendo.2022.967711 -
Experimental Physiology Jul 2021What is the central question of this study? To what extent does testosterone influence haemoglobin formation during male puberty? What is the main finding and its...
NEW FINDINGS
What is the central question of this study? To what extent does testosterone influence haemoglobin formation during male puberty? What is the main finding and its importance? In boys, testosterone might be responsible for about 65% of the increase in haemoglobin mass during puberty. The underlying mechanisms are assumed to be twofold: (i) indirectly, mediated by the increase in lean body mass, and (ii) directly by immediate testosterone effects on erythropoiesis. Thereby, an increase in testosterone of 1 ng/ml is associated with an increase in haemoglobin mass of ∼65 g. These processes are likely to determine endurance performance in adulthood.
ABSTRACT
The amount of haemoglobin during puberty is related to endurance performance in adulthood. During male puberty, testosterone stimulates erythropoiesis and could therefore be used as a marker for later endurance performance. This cross-sectional study aimed to determine the relationship between serum testosterone concentration and haemoglobin mass (Hbmass) in both male and female children and adolescents and to evaluate the possible influences of altitude and training. Three-hundred and thirteen differentially trained boys and girls aged from 9 to 18 years and living at altitudes of 1000 and 2600 m above sea level entered the study. The stage of sexual maturation was determined according to the classification of Tanner. Testosterone was measured by ELISA. Hbmass was determined by CO-rebreathing. Haemoglobin concentration did not change during maturation in girls and was 11% higher during puberty in boys, while Hbmass was elevated by 33% in Tanner stage V compared to stage II in girls (498 ± 77 vs. 373 ± 88 g) and by 95% in boys (832 ± 143 vs. 428 ± 95 g). This difference can most likely be attributed to indirect testosterone influences through an increase in lean body mass (LBM) and to direct testosterone effects on erythropoiesis, which increase the Hbmass by ∼65 g per 1 ng/ml. Altitude and training statuses were not associated with testosterone, but with an increase in Hbmass (altitude by 1.1 g/kg LBM, training by 0.8 g/kg LBM). Changes in Hbmass are closely related to testosterone levels during male puberty. Further studies will show whether testosterone and Hbmass during childhood and adolescence can be used as diagnostic tools for endurance talents.
Topics: Adolescent; Adult; Body Composition; Child; Cross-Sectional Studies; Erythropoiesis; Female; Humans; Male; Puberty; Testosterone
PubMed: 33945170
DOI: 10.1113/EP089433