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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 -
Best Practice & Research. Clinical... Dec 2023The worldwide epidemic of obesity appears to be one of the crucial health problems. One-third of children and adolescents in the United States are classified as either... (Review)
Review
The worldwide epidemic of obesity appears to be one of the crucial health problems. One-third of children and adolescents in the United States are classified as either overweight or obese and 6% of adolescents are severely obese. With the development of high technology, children, and adolescents, spend more time in sedentary life. Together with the availability of consuming fast caloric food, it is almost unavoidable to get an imbalance between caloric intake and caloric expenditure of energy, resulting in the accumulation of fat-energy stores. Obesity has an enormous impact on physical and psychological health and is associated with more than 29 adverse health consequences previously identified in the adult population only, such as type 2 diabetes mellitus, hypertension, metabolic syndrome, postmenopausal breast cancer, and others. In addition, excess adiposity may exert a harmful effect on the reproductive system, resulting in precocious puberty, irregular menstrual cycle, polycystic ovary syndrome, and high-risk sexual behavior. Intervention programs for healthy lifestyle modification, consisting of caloric restriction together with physical activity did not gain the expected efficacy. Other approaches as medical and surgical therapies are currently not evidence-based for the young population. The obesity crisis in children and adolescents requires a better understanding of etiology, pathophysiology, and management of obesity in this unique population. Researchers and physicians must "turn over every stone" to find a solution for deviating obesity ascent.
Topics: Child; Adult; Adolescent; Female; Humans; United States; Diabetes Mellitus, Type 2; Obesity; Overweight; Exercise; Puberty
PubMed: 37708835
DOI: 10.1016/j.bpobgyn.2023.102400 -
Child and Adolescent Psychiatric... Oct 2023As a child and adolescent psychiatrist, I am aware that puberty is a challenging experience for many adolescents and parents. As a parent of a transgender adolescent, I... (Review)
Review
As a child and adolescent psychiatrist, I am aware that puberty is a challenging experience for many adolescents and parents. As a parent of a transgender adolescent, I have seen the ways in which the experience of puberty is similar to and different from that of cisgender adolescents. In this article, I describe my thought process behind going forward with several medical interventions for my transgender child and relate this to broader observations about parents and puberty.
Topics: Adolescent; Child; Humans; Transgender Persons; Parents; Puberty
PubMed: 37739640
DOI: 10.1016/j.chc.2023.05.005 -
Endocrinology and Metabolism Clinics of... Jun 2024Premature pubarche (PP) is a common and usually benign variant of normal puberty most often seen in 5-year-old to 9-year-old children. Some providers routinely order... (Review)
Review
Premature pubarche (PP) is a common and usually benign variant of normal puberty most often seen in 5-year-old to 9-year-old children. Some providers routinely order laboratory testing and a bone age to try to rule out other diagnoses including nonclassic congenital adrenal hyperplasia and gonadal or adrenal tumors. I review the natural history of PP and studies which suggest that without clinical features such as rapid growth and progression or genital enlargement, it is unlikely that a treatable condition will be found. Therefore it is recommended that patients with PP not undergo testing unless there are red flags at the time of the initial visit.
Topics: Humans; Puberty, Precocious; Child; Female; Child, Preschool
PubMed: 38677863
DOI: 10.1016/j.ecl.2024.02.001 -
Nutrients Oct 2023The prevalence of central precocious puberty (CPP) in girls has increased worldwide and is often associated with obesity in childhood as well as high fat/high glycemic... (Review)
Review
The prevalence of central precocious puberty (CPP) in girls has increased worldwide and is often associated with obesity in childhood as well as high fat/high glycemic index diets. Evidence suggests that subjects with obesity present with alterations in appetite-regulating hormones. The arcuate and paraventricular nuclei of the hypothalamus are the centers of action of appetite hormones, as well as the location of gonadotropin-releasing hormone (GnRH) neurons, the activation of which results in the onset of puberty. This anatomical proximity raises the question of possible alterations in appetite-regulating hormones in patients with CPP. Furthermore, diet-induced hypothalamic inflammation constitutes a probable mechanism of the pathophysiology of CPP, as well as alterations in appetite-regulating hormones in young children. In this article, we summarize the evidence investigating whether girls with CPP present with alterations in appetite-regulating hormones. We present evidence that leptin concentrations are elevated in girls with CPP, ghrelin concentrations are lower in girls with CPP, nesfatin-1 and orexin-A concentrations are elevated among girls with premature thelarche, and insulin concentrations are increased in girls with early menarche.
Topics: Female; Child; Humans; Child, Preschool; Puberty, Precocious; Luteinizing Hormone; Appetite; Pediatric Obesity; Gonadotropin-Releasing Hormone; Follicle Stimulating Hormone
PubMed: 37836591
DOI: 10.3390/nu15194306 -
The Journal of Clinical Endocrinology... Aug 2023Endocrine complications are common in pediatric brain tumor patients.
CONTEXT
Endocrine complications are common in pediatric brain tumor patients.
OBJECTIVE
To describe hypothalamic-pituitary-gonadal axis (HPGA) function in patients treated in childhood for a primary brain tumor more than 5 years earlier, in order to identify risk factors for HPGA impairment.
METHODS
We retrospectively included 204 patients diagnosed with a primary brain tumor before 18 years of age and monitored at the pediatric endocrinology unit of the Necker Enfants-Malades University Hospital (Paris, France) between January 2010 and December 2015. Patients with pituitary adenoma or untreated glioma were excluded.
RESULTS
Among patients with suprasellar glioma not treated by radiotherapy, the prevalence of advanced puberty was 65% overall and 70% when the diagnosis occurred before 5 years of age. Medulloblastoma chemotherapy caused gonadal toxicity in 70% of all patients and in 87.5% of those younger than 5 years at diagnosis. In the group with craniopharyngioma, 70% of patients had hypogonadotropic hypogonadism, which was consistently accompanied by growth hormone deficiency.
CONCLUSION
Tumor type, location, and treatment were the risk main factors for HPGA impairment. Awareness that onset can be delayed is essential to guide information of parents and patients, patient monitoring, and timely hormone replacement therapy.
Topics: Child; Humans; Hypothalamic-Pituitary-Gonadal Axis; Retrospective Studies; Brain Neoplasms; Glioma; Puberty
PubMed: 36810692
DOI: 10.1210/clinem/dgad097 -
European Journal of Endocrinology Sep 2023Early puberty suppression (ePS; Tanner stages 2 and 3) through gonadotropin-releasing hormone agonists (GnRHas) and gender-affirming hormones (GAHs) interferes with...
BACKGROUND
Early puberty suppression (ePS; Tanner stages 2 and 3) through gonadotropin-releasing hormone agonists (GnRHas) and gender-affirming hormones (GAHs) interferes with growth and may impact final height (FH).
AIM
To investigate the impact of ePS and GAH on FH in trans boys and trans girls.
METHODS
Retrospective study, including 10 trans boys and 22 trans girls at FH. Bone age (BA) was determined at the start of ePS and at the start of GAH according to Greulich and Pyle; predicted adult height (PAH) was calculated according to Bayley and Pinneau's tables; target height (TH) was calculated as adjusted mean of maternal and paternal height. Target height, PAH, and BA were determined according to sex registered at birth (SRAB) and experienced gender (EG).
RESULTS
The age at the start of PS was 12.37 ± 0.74 years in trans boys and 13.10 ± 1.12 years in trans girls. Total height gain since the start of ePS in trans boys was 14.62 ± 4.08 cm, with 70% achieved before the start of GAH. In trans girls, it was 20.68 ± 7.66 cm, with 61% achieved before GAH. Target height for SRAB was the most accurate predictor for FH in both trans boys and girls: the difference with FH was 1.57 cm ± 3.1 (P = .168) and -0.98 cm ± 4.17 (P = .319), respectively. Also the difference between FH and PAH at the start of PS for SRAB was nonsignificant in both trans boys and girls (2.62 cm ± 3.79, P = .056 and -2.35 cm ± 5.2, P = .051, respectively).
CONCLUSION
Early puberty suppression and GAH do not impact FH, supporting the safety of the treatment; however, trans adolescents achieve a FH in line with SRAB, rather than EG.
Topics: Adult; Infant, Newborn; Male; Female; Adolescent; Humans; Transgender Persons; Retrospective Studies; Family; Puberty, Precocious; Puberty
PubMed: 37703317
DOI: 10.1093/ejendo/lvad125 -
Brain Research Bulletin Aug 2023Illness is often predicated long before the manifestation of its symptoms. Exposure to stressful experiences particularly during critical periods of development, such as... (Review)
Review
Illness is often predicated long before the manifestation of its symptoms. Exposure to stressful experiences particularly during critical periods of development, such as puberty and adolescence, can induce various physical and mental illnesses. Puberty is a critical period of maturation for neuroendocrine systems, such as the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes. Exposure to adverse experiences during puberty can impede normal brain reorganizing and remodelling and result in enduring consequences on brain functioning and behaviour. Stress responsivity differs between the sexes during the pubertal period. This sex difference is partly due to differences in circulating sex hormones between males and females, impacting stress and immune responses differently. The effects of stress during puberty on physical and mental health remains under-examined. The purpose of this review is to summarize the most recent findings pertaining to age and sex differences in HPA axis, HPG axis, and immune system development, and describe how disruption in the functioning of these systems can propagate disease. Lastly, we delve into the notable neuroimmune contributions, sex differences, and the mediating role of the gut microbiome on stress and health outcomes. Understanding the enduring consequences of adverse experiences during puberty on physical and mental health will allow a greater proficiency in treating and preventing stress-related diseases early in development.
Topics: Adolescent; Humans; Male; Female; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Puberty; Sex Characteristics; Brain
PubMed: 37422090
DOI: 10.1016/j.brainresbull.2023.110701 -
Frontiers in Endocrinology 2023Noonan syndrome (NS) is a genetic multisystem disorder characterised by variable clinical manifestations including dysmorphic facial features, short stature, congenital...
BACKGROUND
Noonan syndrome (NS) is a genetic multisystem disorder characterised by variable clinical manifestations including dysmorphic facial features, short stature, congenital heart disease, renal anomalies, lymphatic malformations, chest deformities, cryptorchidism in males.
METHODS
In this narrative review, we summarized the available data on puberty and gonadal function in NS subjects and the role of the RAS/mitogen-activated protein kinase (MAPK) signalling pathway in fertility. In addition, we have reported our personal experience on pubertal development and vertical transmission in NS.
CONCLUSIONS
According to the literature and to our experience, NS patients seem to have a delay in puberty onset compared to the physiological timing reported in healthy children. Males with NS seem to be at risk of gonadal dysfunction secondary not only to cryptorchidism but also to other underlying developmental factors including the MAP/MAPK pathway and genetics. Long-term data on a large cohort of males and females with NS are needed to better understand the impact of delayed puberty on adult height, metabolic profile and well-being. The role of genetic counselling and fertility related-issues is crucial.
Topics: Male; Child; Adult; Female; Humans; Noonan Syndrome; Cryptorchidism; Gonads; Puberty; Mitogen-Activated Protein Kinases
PubMed: 37576960
DOI: 10.3389/fendo.2023.1213098 -
Biology Letters Sep 2023There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One...
There is considerably greater variation in metabolic rates between men than between women, in terms of basal, activity and total (daily) energy expenditure (EE). One possible explanation is that EE is associated with male sexual characteristics (which are known to vary more than other traits) such as musculature and athletic capacity. Such traits might be predicted to be most prominent during periods of adolescence and young adulthood, when sexual behaviour develops and peaks. We tested this hypothesis on a large dataset by comparing the amount of male variation and female variation in total EE, activity EE and basal EE, at different life stages, along with several morphological traits: height, fat free mass and fat mass. Total EE, and to some degree also activity EE, exhibit considerable greater male variation (GMV) in young adults, and then a decreasing GMV in progressively older individuals. Arguably, basal EE, and also morphometrics, do not exhibit this pattern. These findings suggest that single male sexual characteristics may not exhibit peak GMV in young adulthood, however total and perhaps also activity EE, associated with many morphological and physiological traits combined, do exhibit GMV most prominently during the reproductive life stages.
Topics: Adolescent; Young Adult; Female; Humans; Male; Adult; Puberty; Sexual Behavior; Reproduction; Energy Metabolism; Phenotype
PubMed: 37727077
DOI: 10.1098/rsbl.2023.0152