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Children (Basel, Switzerland) Oct 2023Nutrients have an enormous impact on many hormonal systems and aspects of health, and nutrition status is a crucial regulator of growth and pubertal development in... (Review)
Review
Nutrients have an enormous impact on many hormonal systems and aspects of health, and nutrition status is a crucial regulator of growth and pubertal development in children and adolescents. In this narrative review, we explore the connection between these feeding methods and the timing of puberty to provide a clearer understanding of how infant nutrition might contribute to the early development of puberty. Puberty is a key stage in the transition from childhood to adulthood and the timing of puberty represents a significant biological milestone of growth. Breast milk seems to have a pivotal role in puberty onset, mainly due to its dynamism, which shape indirectly the gut microbiota in early life, besides direct exposure of the baby to the milk microbiota through gut-breast axis. Concerning breast and formula milk and their effects on the onset of puberty, a protective role of the former occurs. As for the potential harmful effects of soy-based formulas and the isoflavones that they contain, the studies reported demonstrate conflicting opinions, underlining the need for further research on this topic. A healthy and well-nourished diet from the earliest stages of life has significant preventive potential for overall well-being, reducing the risk of many health problems later in life.
PubMed: 37892349
DOI: 10.3390/children10101686 -
Nature Communications Dec 2023Innervation of the hypothalamic median eminence by Gonadotropin-Releasing Hormone (GnRH) neurons is vital to ensure puberty onset and successful reproduction. However,...
Innervation of the hypothalamic median eminence by Gonadotropin-Releasing Hormone (GnRH) neurons is vital to ensure puberty onset and successful reproduction. However, the molecular and cellular mechanisms underlying median eminence development and pubertal timing are incompletely understood. Here we show that Semaphorin-6A is strongly expressed by median eminence-resident oligodendrocytes positioned adjacent to GnRH neuron projections and fenestrated capillaries, and that Semaphorin-6A is required for GnRH neuron innervation and puberty onset. In vitro and in vivo experiments reveal an unexpected function for Semaphorin-6A, via its receptor Plexin-A2, in the control of median eminence vascular permeability to maintain neuroendocrine homeostasis. To support the significance of these findings in humans, we identify patients with delayed puberty carrying a novel pathogenic variant of SEMA6A. In all, our data reveal a role for Semaphorin-6A in regulating GnRH neuron patterning by tuning the median eminence vascular barrier and thereby controlling puberty onset.
Topics: Humans; Gonadotropin-Releasing Hormone; Median Eminence; Capillary Permeability; Neurons; Puberty; Semaphorins
PubMed: 38062045
DOI: 10.1038/s41467-023-43820-z -
Journal of Clinical Medicine Nov 2023A cough is one of several defensive responses that protect and clear the airways of inhaled, aspirated or locally produced chemicals and matter. The neural components... (Review)
Review
A cough is one of several defensive responses that protect and clear the airways of inhaled, aspirated or locally produced chemicals and matter. The neural components needed to initiate a cough begin to develop in utero, and at birth the airways and lungs already have a rich supply of sensory and motor-neural innervation. However, a cough is not always the primary defensive response to airway challenge in very young infants, but instead develops in the first postnatal months and matures further into puberty. Consequently, the clinical presentation of a troublesome cough in children may not be the same as in adults, exemplified by important differences in cough sensitivity and hypersensitivity between children and adults. This review will summarise key anatomical and functional concepts in airway neurobiology that may improve understanding of coughs in children.
PubMed: 38068335
DOI: 10.3390/jcm12237285 -
Current Opinion in Endocrinology,... Feb 2024Primary mitochondrial diseases are one of the most prevalent groups of multisystem genetic disorders. Endocrinopathies associated with mitochondrial diseases may have... (Review)
Review
PURPOSE OF REVIEW
Primary mitochondrial diseases are one of the most prevalent groups of multisystem genetic disorders. Endocrinopathies associated with mitochondrial diseases may have clinical features that are distinct from the more common forms. We provide an overview of mitochondrial disorder genetics and phenotypes, focusing on recent studies regarding identification and treatment of associated endocrinopathies.
RECENT FINDINGS
Known endocrine phenotypes of mitochondrial disorders continue to expand, and now include growth hormone deficiency, hypogonadism, precocious puberty, hypoparathyroidism, hypo- and hyperthyroidism, diabetes, and adrenal insufficiency. Recent studies suggest several genotype-phenotype correlations, including those related to nuclear variants. Diagnosis is important, as special considerations should be made in the management of endocrinopathies in mitochondrial patients. Finally, new mitochondrial replacement strategies may soon be available for women interested in preventing mitochondrial disease transmission to offspring.
SUMMARY
Patients with multiple endocrinopathies or atypical endocrinopathies should be evaluated for primary mitochondrial disease, as a diagnosis may impact management of these individuals.
Topics: Humans; Female; Endocrine System Diseases; Diabetes Mellitus; Puberty, Precocious; Mitochondrial Diseases; Hyperthyroidism; Adrenal Insufficiency
PubMed: 38047549
DOI: 10.1097/MED.0000000000000848 -
Cancer Epidemiology Aug 2023Several studies have linked increased risk of osteosarcoma with tall stature, high birthweight, and early puberty, although evidence is inconsistent. We used genetic...
INTRODUCTION
Several studies have linked increased risk of osteosarcoma with tall stature, high birthweight, and early puberty, although evidence is inconsistent. We used genetic risk scores (GRS) based on established genetic loci for these traits and evaluated associations between genetically inferred birthweight, height, and puberty timing with osteosarcoma.
METHODS
Using genotype data from two genome-wide association studies, totaling 1039 cases and 2923 controls of European ancestry, association analyses were conducted using logistic regression for each study and meta-analyzed to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were conducted by case diagnosis age, metastasis status, tumor location, tumor histology, and presence of a known pathogenic variant in a cancer susceptibility gene.
RESULTS
Genetically inferred higher birthweight was associated with an increased risk of osteosarcoma (OR =1.59, 95% CI 1.07-2.38, P = 0.02). This association was strongest in cases without metastatic disease (OR =2.46, 95% CI 1.44-4.19, P = 9.5 ×10). Although there was no overall association between osteosarcoma and genetically inferred taller stature (OR=1.06, 95% CI 0.96-1.17, P = 0.28), the GRS for taller stature was associated with an increased risk of osteosarcoma in 154 cases with a known pathogenic cancer susceptibility gene variant (OR=1.29, 95% CI 1.03-1.63, P = 0.03). There were no significant associations between the GRS for puberty timing and osteosarcoma.
CONCLUSION
A genetic propensity to higher birthweight was associated with increased osteosarcoma risk, suggesting that shared genetic factors or biological pathways that affect birthweight may contribute to osteosarcoma pathogenesis.
PubMed: 37596165
DOI: 10.1016/j.canep.2023.102432 -
Journal of Pediatric Endocrinology &... Oct 2023Artificial Intelligence (AI) is integrating itself throughout the medical community. AI's ability to analyze complex patterns and interpret large amounts of data will... (Review)
Review
Artificial Intelligence (AI) is integrating itself throughout the medical community. AI's ability to analyze complex patterns and interpret large amounts of data will have considerable impact on all areas of medicine, including pediatric endocrinology. In this paper, we review and update the current studies of AI in pediatric endocrinology. Specific topics that are addressed include: diabetes management, bone growth, metabolism, obesity, and puberty. Becoming knowledgeable and comfortable with AI will assist pediatric endocrinologists, the goal of the paper.
Topics: Child; Humans; Artificial Intelligence; Endocrinology
PubMed: 37589444
DOI: 10.1515/jpem-2023-0287 -
International Journal of Molecular... Nov 2023Human sexual and reproductive development is regulated by the hypothalamic-pituitary-gonadal (HPG) axis, which is primarily controlled by the gonadotropin-releasing... (Review)
Review
Human sexual and reproductive development is regulated by the hypothalamic-pituitary-gonadal (HPG) axis, which is primarily controlled by the gonadotropin-releasing hormone (GnRH) acting on its receptor (GnRHR). Dysregulation of the axis leads to conditions such as congenital hypogonadotropic hypogonadism (CHH) and delayed puberty. The pathophysiology of GnRHR makes it a potential target for treatments in several reproductive diseases and in congenital adrenal hyperplasia. GnRHR belongs to the G protein-coupled receptor family and its GnRH ligand, when bound, activates several complex and tissue-specific signaling pathways. In the pituitary gonadotrope cells, it triggers the G protein subunit dissociation and initiates a cascade of events that lead to the production and secretion of the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) accompanied with the phospholipase C, inositol phosphate production, and protein kinase C activation. Pharmacologically, GnRHR can be modulated by synthetic analogues. Such analogues include the agonists, antagonists, and the pharmacoperones. The agonists stimulate the gonadotropin release and lead to receptor desensitization with prolonged use while the antagonists directly block the GnRHR and rapidly reduce the sex hormone production. Pharmacoperones include the most recent GnRHR therapeutic approaches that directly correct the misfolded GnRHRs, which are caused by genetic mutations and hold serious promise for CHH treatment. Understanding of the GnRHR's genomic and protein structure is crucial for the most appropriate assessing of the mutation impact. Such mutations in the GNRHR are linked to normosmic hypogonadotropic hypogonadism and lead to various clinical symptoms, including delayed puberty, infertility, and impaired sexual development. These mutations vary regarding their mode of inheritance and can be found in the homozygous, compound heterozygous, or in the digenic state. GnRHR expression extends beyond the pituitary gland, and is found in reproductive tissues such as ovaries, uterus, and prostate and non-reproductive tissues such as heart, muscles, liver and melanoma cells. This comprehensive review explores GnRHR's multifaceted role in human reproduction and its clinical implications for reproductive disorders.
Topics: Female; Male; Humans; Receptors, LHRH; Puberty, Delayed; Hypogonadism; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Follicle Stimulating Hormone; Klinefelter Syndrome
PubMed: 37958948
DOI: 10.3390/ijms242115965 -
Frontiers in Pediatrics 2023The aim of this study was to evaluate the potential association between early onset puberty and the risk of different forms of obesity in children. (Review)
Review
OBJECTIVES
The aim of this study was to evaluate the potential association between early onset puberty and the risk of different forms of obesity in children.
METHODS
The databases PubMed, EMBASE, Web of Science and Cochrane Library were systematically searched for relevant studies. The odds ratio (OR) and 95% confidence interval (CI) of obesity in precocious puberty were calculated using Stata software 14.0. A fixed-effects model was used if > 0.1 and ≤ 50%. Otherwise, a random-effects model was used. Publication bias was assessed using funnel plots and Egger's test.
RESULT
The pooling analysis showed that precocious puberty in girls was associated with a higher risk of obesity (OR = 1.98; 95% CI: 1.76-2.24; = 0.00%, < 0.001). Girls with a history of precocious puberty were found to have an increased risk of general obesity (OR = 2.03; 95% CI: 1.62-2.55; = 22.2%, < 0.001), central obesity (OR = 1.96; 95% CI: 1.70-2.26; = 0.00%, < 0.001), and overweight (OR = 2.03; 95% CI: 1.68-2.46; = 5.1%, < 0.001). The pooled analysis showed that precocious puberty in boys was not associated with an increased risk of obesity (OR = 1.14; 95% CI: 0.86-1.51; = 50.6%, = 0.369). In boys, the occurrence of precocious puberty was not associated with an elevated risk of general obesity (OR = 0.96; 95% CI: 0.40-2.27; = 79.6%, = 0.922), central obesity (OR = 1.17; 95% CI: 0.96-1.43; = 0.00%, = 0.125), or overweight (OR = 1.03; 95% CI: 0.56-1.88; = 74.4%, = 0.930).
CONCLUSION
This meta-analysis suggests that the onset of puberty at an early age in girls is associated with an increased risk of obesity, however precocious puberty in boy was not associated with an increased risk of obesity. These findings highlight that precocious puberty should be considered an independent risk factor for obesity in girls.
SYSTEMATIC REVIEW REGISTRATION
CRD42023404479.
PubMed: 37635793
DOI: 10.3389/fped.2023.1226933