-
Italian Journal of Pediatrics Mar 2020Pubertal timing is known to be influenced by interactions among various genetic, nutritional, environmental and socio-economic factors, although the ultimate mechanisms...
BACKGROUND
Pubertal timing is known to be influenced by interactions among various genetic, nutritional, environmental and socio-economic factors, although the ultimate mechanisms underlying the increase in pulsatile GnRH secretion at puberty have yet to be fully elucidated. The aim of our research was to verify the role of KISSR1 (previously named GPR54) and MKRN3 genes on pubertal timing.
METHODS
We analyzed the DNA sequence of these genes in 13 girls affected by central precocious puberty (CPP) who showed onset of puberty before 8 years of age, and in 6 girls affected by early puberty (EP) between 8 and 10 years of age.
RESULTS
Direct sequencing of the KISS1R (GPR54) gene revealed two SNPs. One SNP is a missense variant (rs 350,132) that has been previously reported in connection to CPP in Korean girls. The other variant that we found in the GPR54 gene (rs764046557) was a missense SNP located in exon 5 at position 209 of the aminoacid. We identified this variant in only one CPP patient. Automatic sequencing of MKRN3 in all patients revealed three variants in eight subjects. In 6 out of 19 (31.5%) patients (3/13 CPP patients and 3/6 EP patients) we found the synonymous variant c.663C > T (rs2239669). Another synonymous variant (rs140467331) was found in one of our CPP patients, as well as one missense variant (rs760981395) in another CPP patient.
CONCLUSION
In conclusion, we identified sequence variations of the KISS1R and MKRN3 genes, two of the most frequent genetic causes of ICPP. Our results suggest that these variants might be inducible factors in the pathogenesis of CPP.
Topics: Age Factors; Child; Female; Humans; Italy; Mutation, Missense; Polymorphism, Single Nucleotide; Puberty, Precocious; Receptors, Kisspeptin-1; Sexual Development; Ubiquitin-Protein Ligases
PubMed: 32228714
DOI: 10.1186/s13052-020-0808-6 -
Italian Journal of Pediatrics Apr 2022Increased incidence of central precocious puberty (CPP) after coronavirus infectious disease-19 lockdown has been reported. Our study aims in investigating changes in...
BACKGROUND
Increased incidence of central precocious puberty (CPP) after coronavirus infectious disease-19 lockdown has been reported. Our study aims in investigating changes in CPP rates and in sleep patterns in CPP and healthy controls.
METHODS
CPP were retrospectively evaluated from April 2020 to April 2021. Parents of girls diagnosed with CPP during lockdown and of matched healthy controls filled out a questionnaire about sleep disturbances (SDSC questionnaire) and sleep schedules.
RESULTS
Thirty-five CPP and 37 controls completed the survey. Incidence of new CPP cases significantly increased in 2020-2021 compared to 2017-2020 (5:100 vs 2:100, p = 0.02). Sleep disturbance rates did not differ between CPP and healthy controls before lockdown. During lockdown, CPP reported higher rates of sleep disturbs for total score (p = 0.005), excessive somnolence (p = 0.049), sleep breathing disorders (p = 0.049), and sleep-wake transition disorders (p = 0.005). Moreover, CPP group more frequently shifted toward later bedtime (p = 0.03) during lockdown compared to controls. Hours of sleep and smartphone exposure around bedtime did not differ between groups.
CONCLUSIONS
Our study confirms the observation of increased incidence of CPP after lockdown measures. Additionally, CPP showed higher rates of sleep disturbances and later bedtime compared to controls. The causality link between sleep disturbances and CPP should be further investigated to gain knowledge in this association.
Topics: COVID-19; Communicable Disease Control; Female; Humans; Pandemics; Puberty, Precocious; Retrospective Studies; Sleep; Sleep Wake Disorders
PubMed: 35461296
DOI: 10.1186/s13052-022-01256-z -
Human Reproduction (Oxford, England) Feb 2021Is in utero exposure to mercury associated with the risk of precocious puberty?
STUDY QUESTION
Is in utero exposure to mercury associated with the risk of precocious puberty?
SUMMARY ANSWER
Prenatal exposure to high levels of mercury was associated with increased risk of precocious puberty, which was strengthened by concomitant maternal cardiometabolic conditions and adverse birth outcomes.
WHAT IS KNOWN ALREADY
The developing fetus is sensitive to mercury, a well-known endocrine disruptor which impacts the endocrine and reproductive system.
STUDY DESIGN, SIZE, DURATION
This study included 1512 mother-child pairs from the Boston Birth Cohort, a longitudinal cohort which recruited at birth and followed prospectively up to 21 years of age.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Mother-child pairs, from a predominantly urban minority population, were enrolled from 2002 to 2013. Prenatal exposure was assessed by maternal mercury concentration in red blood cells (RBCs) collected at 1-3 days after delivery. Precocious puberty was defined based on International Classification of Disease codes. Cox proportional hazards models were applied to the association between maternal mercury concentrations and the risk of precocious puberty.
MAIN RESULTS AND THE ROLE OF CHANCE
The median (interquartile range) of maternal mercury concentrations among children with and without precocious puberty were 3.4 (1.9-4.6) µg/l and 2.0 (1.0-3.7) µg/l, respectively. Compared to those in the lowest tertile for mercury, the highest tertile was associated with increased risk of precocious puberty, with an adjusted hazard ratio (HR) of 2.41, 95% CI: 1.16-5.03. In addition, concomitant maternal cardiometabolic conditions and adverse birth outcomes strengthened the effects of mercury on the risk of precocious puberty. The highest risk of precocious puberty was observed among children who had adverse birth outcomes and whose mothers had high RBC-mercury concentrations along with cardiometabolic conditions, with an HR of 4.76 (95% CI: 1.66-13.60) compared to children with favorable profiles of all three risk factors.
LIMITATIONS, REASONS FOR CAUTION
Precocious puberty was defined based on medical records, not on a direct assessment, which may have led to underdiagnosis and the inability to make a subclassification. The study included a predominately urban, low-income, minority population and as such our findings may not be widely generalizable.
WIDER IMPLICATIONS OF THE FINDINGS
Prenatal Hg exposure was associated with an increased risk of precocious puberty. This risk was strengthened by concomitant maternal cardiometabolic conditions during pregnancy and adverse birth outcomes.
STUDY FUNDING/COMPETING INTEREST(S)
This study was funded by the NIH/National Institute of Environmental Health Sciences, NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Health Resources and Services Administration of the U.S. Department of Health and Human Services. The authors declare no conflicts of interest.
TRIAL REGISTRATION NUMBER
N/A.
Topics: Boston; Child; Cohort Studies; Female; Humans; Infant, Newborn; Mercury; Pregnancy; Prenatal Exposure Delayed Effects; Prospective Studies; Puberty, Precocious
PubMed: 33367618
DOI: 10.1093/humrep/deaa315 -
Frontiers in Endocrinology 2022In the last decade, deep learning methods have garnered a great deal of attention in endocrinology research. In this article, we provide a summary of current deep... (Review)
Review
In the last decade, deep learning methods have garnered a great deal of attention in endocrinology research. In this article, we provide a summary of current deep learning applications in endocrine disorders caused by either precocious onset of adult hormone or abnormal amount of hormone production. To give access to the broader audience, we start with a gentle introduction to deep learning and its most commonly used architectures, and then we focus on the research trends of deep learning applications in thyroid dysfunction classification and precocious puberty diagnosis. We highlight the strengths and weaknesses of various approaches and discuss potential solutions to different challenges. We also go through the practical considerations useful for choosing (and building) the deep learning model, as well as for understanding the thought process behind different decisions made by these models. Finally, we give concluding remarks and future directions.
Topics: Humans; Puberty, Precocious; Deep Learning; Thyroid Gland; Hormones
PubMed: 36339395
DOI: 10.3389/fendo.2022.959546 -
BMC Genetics Jul 2018The present study aimed to investigate the association between MKRN3 and LIN28B gene polymorphisms and precocious puberty in Korean boys and girls.
BACKGROUND
The present study aimed to investigate the association between MKRN3 and LIN28B gene polymorphisms and precocious puberty in Korean boys and girls.
RESULTS
Children 7 to 9 years of age in 2011 to 2012 who were part of the Ewha Birth & Growth Cohort Study were recruited for this study. A total of 103 girls and 70 boys were included in the analyses. Seven girls and 26 boys were identified to have precocious puberty. Among four single nucleotide polymorphisms (SNPs) of MKRN3 and two SNPs of LIN28B examined, three SNPs (rs2239669, rs6576457, and rs12441827) showed significant associations with precocious puberty in additive models in boys but no significance was found in any SNPs in girls. From the logistic regression analysis, boys with TT alleles in rs12441827 had about a four-times greater risk for precocious puberty when compared to C allele carriers (OR = 3.95, 95% CI = 1.27-12.32 in model 1). eQTL analysis revealed that SNPs of statistical significance from our study did not show the variation in expression profiles nor found in the database.
CONCLUSIONS
This study supports the impact of MKRN3 SNP rs12441827 on precocious puberty in Korean boys. The results add a further aspect to genetic association in precocious puberty along with complex interactions of environmental, nutritional and socioeconomic factors.
Topics: Child; Cohort Studies; Female; Humans; Male; Polymorphism, Single Nucleotide; Puberty, Precocious; RNA-Binding Proteins; Republic of Korea; Ribonucleoproteins; Sex Factors; Ubiquitin-Protein Ligases
PubMed: 30053798
DOI: 10.1186/s12863-018-0658-z -
Endocrine Development 2016There are many etiologies of peripheral precocious puberty (PPP) with diverse manifestations resulting from exposure to androgens, estrogens, or both. The clinical... (Review)
Review
There are many etiologies of peripheral precocious puberty (PPP) with diverse manifestations resulting from exposure to androgens, estrogens, or both. The clinical presentation depends on the underlying process and may be acute or gradual. The primary goals of therapy are to halt pubertal development and restore sex steroids to prepubertal values. Attenuation of linear growth velocity and rate of skeletal maturation in order to maximize height potential are additional considerations for many patients. McCune-Albright syndrome (MAS) and familial male-limited precocious puberty (FMPP) represent rare causes of PPP that arise from activating mutations in GNAS1 and the LH receptor gene, respectively. Several different therapeutic approaches have been investigated for both conditions with variable success. Experience to date suggests that the ideal therapy for precocious puberty secondary to MAS in girls remains elusive. In contrast, while the number of treated patients remains small, several successful therapeutic options for FMPP are available.
Topics: Adolescent; Female; Fibrous Dysplasia, Polyostotic; Humans; Male; Puberty, Precocious
PubMed: 26680582
DOI: 10.1159/000438895 -
Frontiers in Endocrinology 2022To compared the incidence rates and clinical features of precocious girls before and during the COVID-19 pandemic among Shanghai school-aged girls, and explored the...
OBJECTIVE
To compared the incidence rates and clinical features of precocious girls before and during the COVID-19 pandemic among Shanghai school-aged girls, and explored the potential mechanisms.
METHODS
This cross-sectional study collected medical data about precocious girls between 2016 and 2020 from Shanghai Children's Medical Center. Data of inpatient precocious girls from March to August in 2016-2019 (n=246) and 2020 (n=237) were collected. Subjects with abnormal brain and pituitary gland MRI reports, other endocrine diseases or chronic diseases were excluded. Finally, 209 precocious girls were included in the 2016-2019 group and 191 precocious girls were include in the 2020 group. Monthly incidence rates and clinical features were compared between before and during the COVID-19 pandemic. Linear regression models were used to examine the associations between biomarkers to explore the potential mechanisms.
RESULTS
Monthly incidence rates of precocious puberty in outpatient girls from March to December 2020 (0.44-1.36%) and in inpatient girls from March to August 2020 (27.04-47.83%) were higher than those in 2016-2019 (0.30-0.52% and 10.53-18.42%, respectively). Serum concentrations of GnRH were higher in the 2020 group than in the 2016-2019 group (2.81 vs 1.99 mg/L). Serum concentrations of MKRN3 (1.02 vs 1.93 ng/ml) and ghrelin (0.38 vs 0.88 ng/ml) were lower in the 2020 group than in the 2016-2019 group. Moreover, the serum concentration of ghrelin was positively associated with the serum concentration of MKRN3 [0.891 (, 0.612, 1.171); 0.001].
CONCLUSIONS
These findings suggest an increased incidence of precocious puberty during the COVID-19 pandemic among Shanghai school-aged girls, which may be associated with decreased serum concentrations of MKRN3 and ghrelin, and indicated ghrelin as a potential regulatory mechanism of puberty.
Topics: COVID-19; Child; China; Cross-Sectional Studies; Female; Ghrelin; Humans; Pandemics; Puberty, Precocious; Ubiquitin-Protein Ligases
PubMed: 35392135
DOI: 10.3389/fendo.2022.839895 -
British Medical Journal (Clinical... Feb 1983
Topics: Adolescent; Child; Cyproterone; Female; Humans; Male; Medroxyprogesterone; Pituitary Hormone-Releasing Hormones; Puberty, Precocious
PubMed: 6402194
DOI: 10.1136/bmj.286.6366.664 -
Frontiers in Endocrinology 2023(-)-Epigallocatechin-3-gallate (EGCG) has preventive effects on obesity-related precocious puberty, but its underlying mechanism remains unclear. The aim of this study... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
(-)-Epigallocatechin-3-gallate (EGCG) has preventive effects on obesity-related precocious puberty, but its underlying mechanism remains unclear. The aim of this study was to integrate metabolomics and network pharmacology to reveal the mechanism of EGCG in the prevention of obesity-related precocious puberty.
MATERIALS AND METHODS
A high-performance liquid chromatography-electrospray ionization ion-trap tandem mass spectrometry (LC-ESI-MS/MS) was used to analyze the impact of EGCG on serum metabolomics and associated metabolic pathways in a randomized controlled trial. Twelve weeks of EGCG capsules were given to obese girls in this trail. Additionally, the targets and pathways of EGCG in preventing obesity-related precocious puberty network pharmacology were predicted using network pharmacology. Finally, the mechanism of EGCG prevention of obesity-related precocious puberty was elucidated through integrated metabolomics and network pharmacology.
RESULTS
Serum metabolomics screened 234 endogenous differential metabolites, and network pharmacology identified a total of 153 common targets. These metabolites and targets mainly enrichment pathways involving endocrine-related pathways (estrogen signaling pathway, insulin resistance, and insulin secretion), and signal transduction (PI3K-Akt, MAPK, and Jak-STAT signaling pathways). The integrated metabolomics and network pharmacology indicated that AKT1, EGFR, ESR1, STAT3, IGF1, and MAPK1 may be key targets for EGCG in preventing obesity-related precocious puberty.
CONCLUSION
EGCG may contribute to preventing obesity-related precocious puberty through targets such as AKT1, EGFR, ESR1, STAT3, IGF1, and MAPK1 and multiple signaling pathways, including the estrogen, PI3K-Akt, MAPK, and Jak-STAT pathways. This study provided a theoretical foundation for future research.
Topics: Humans; Female; Network Pharmacology; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Puberty, Precocious; Tandem Mass Spectrometry; Metabolomics; Estrogens; ErbB Receptors
PubMed: 37334310
DOI: 10.3389/fendo.2023.1159657 -
Journal of Pediatric Endocrinology &... Nov 2016
Topics: Adolescent; Animals; Child; Chronic Disease; Disease Progression; Endocrine Disruptors; Environmental Pollutants; Family Health; Female; Genetic Variation; Humans; Male; Precision Medicine; Puberty, Delayed; Puberty, Precocious
PubMed: 27771625
DOI: 10.1515/jpem-2016-0394