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Hormone Research in Paediatrics 2022Spanning from bench to bedside, the history of normal and precocious puberty is characterized by a series of remarkable advances that have illuminated reproductive... (Review)
Review
Spanning from bench to bedside, the history of normal and precocious puberty is characterized by a series of remarkable advances that have illuminated reproductive physiology and profoundly impacted clinical care. Early recognition of the hypothalamic and pituitary control of ovarian and testicular function led to the identification of GnRH as the key driver of pubertal onset. Decades later, discovery of the kisspeptin system further refined our understanding of human reproductive neuroendocrinology. Development of long-acting analogs of GnRH revolutionized the treatment of precocious puberty worldwide and ushered in the current era of an ever-expanding therapeutic armamentarium. Identification of monogenic etiologies of precocious puberty has further illustrated the exquisite complexity that comprises neurosecretory modulation of the hypothalamic GnRH neuron and may well lead to exciting novel targeted therapies.
Topics: Humans; Gonadotropin-Releasing Hormone; Neuroendocrinology; Neurons; Puberty; Puberty, Precocious
PubMed: 36446322
DOI: 10.1159/000526464 -
British Journal of Nursing (Mark Allen... Mar 2021This article provides a brief overview of adolescence. It highlights the key physical changes related to puberty and identifies the latest understanding of neurological... (Review)
Review
This article provides a brief overview of adolescence. It highlights the key physical changes related to puberty and identifies the latest understanding of neurological development in young people. It is also recognised, within the article, that this period of rapid change can have an impact on social and emotional wellbeing. There are conditions that typically have an onset during adolescence, examples of this are offered. The term 'adolescence' is used to describe the stage of development and growth and 'young people' is used throughout to refer to the individuals.
Topics: Adolescent; Humans; Physical Examination; Puberty
PubMed: 33733842
DOI: 10.12968/bjon.2021.30.5.272 -
Sexual Development : Genetics,... 2022Puberty is a complex transitional phase in which reproductive capacity is achieved. There is a very wide variation in the age range of the onset of puberty, which... (Review)
Review
Puberty is a complex transitional phase in which reproductive capacity is achieved. There is a very wide variation in the age range of the onset of puberty, which follows a familial, ethnic, and sex pattern. The hypothalamic-pituitary-gonadal axis and several genetic, environmental, and nutritional factors play an important role in the onset of and throughout puberty. Recently, there has been significant progress in identifying factors that affect normal pubertal timing. Different studies have identified single nucleotide polymorphisms (SNPs) that affect pubertal timing in both sexes and across ethnic groups. Single genes are implicated in both precocious and delayed puberty, and epigenetic mechanisms have been suggested to affect the development and function of the GnRH neuronal network and responsiveness of end organs. All these factors can influence normal puberty timing, precocious puberty, and delayed puberty. The objective of this review is to describe recent findings related to the genetic and epigenetic control of puberty and highlight the need to deepen the knowledge of the regulatory mechanisms of this process in the normal and abnormal context.
Topics: Epigenesis, Genetic; Female; Gonadotropin-Releasing Hormone; Humans; Male; Puberty; Puberty, Precocious
PubMed: 34649256
DOI: 10.1159/000519039 -
European Journal of Pediatrics May 2021Gender incongruence (GI) is defined as a condition in which the gender identity of a person does not align with the gender assigned at birth. Awareness and more social... (Review)
Review
Gender incongruence (GI) is defined as a condition in which the gender identity of a person does not align with the gender assigned at birth. Awareness and more social acceptance have paved the way for early medical intervention about two decades ago and are now part of good clinical practice although much robust data is lacking. Medical and mental treatment in adolescents with GI is complex and is recommended to take place within a team of mental health professionals, psychiatrists, endocrinologists, and other healthcare providers. The somatic treatment generally consists of the use of GnRH analogues to prevent the progression of biological puberty and subsequently gender-affirming hormonal treatment to develop sex characteristics of the self-identified gender and surgical procedures. However to optimize treatment regimens, long-term follow-up and additional studies are still needed. What is known • The prevalence of gender dysphoria increased significantly in the past years and can lead to significant complaints and burdens especially during puberty. • Pubertal suppression and gender-affirmed treatment can be effectively used in adolescence with gender dysphoria. What is new • Transgender mental and medical healthcare is a long-lasting process during which not only the child/adolescent with GI but also their parents/family have to be counseled in making choices about their social, medical, and legal transitions. • There are an increasing number of transgender persons defining as nonbinary. Therefore, an individualized approach by an experienced team is necessary.
Topics: Adolescent; Child; Female; Follow-Up Studies; Gender Dysphoria; Gender Identity; Humans; Infant, Newborn; Male; Puberty; Transgender Persons
PubMed: 33337526
DOI: 10.1007/s00431-020-03906-y -
Frontiers in Endocrinology 2022Puberty is a critical phase of life associated with physiological changes related to sexual maturation, and represents a complex process regulated by multiple endocrine... (Review)
Review
Puberty is a critical phase of life associated with physiological changes related to sexual maturation, and represents a complex process regulated by multiple endocrine and genetic controls. Puberty is driven by hormones, and it can impact the gut microbiome (GM). GM differences between sex emerge at puberty onset, confirming a relationship between microbiota and sex hormones. In this narrative review, we present an overview of precocious pubertal development and the changes in the GM in precocious puberty (PP) in order to consider the role of the sex hormone-gut microbiome axis from the perspective of pediatric endocrinology. Bidirectional interactions between the GM and sex hormones have been proposed in different studies. Although the evidence on the interaction between microbiota and sex hormones remains limited in pediatric patients, the evidence that GM alterations may occur in girls with central precocious puberty (CPP) represents an interesting finding for the prediction and prevention of PP. Deepening the understanding of the connection between the sex hormones and the role of microbiota changes can lead to the implementation of microbiota-targeted therapies in pubertal disorders by offering a pediatric endocrinology perspective.
Topics: Female; Humans; Child; Puberty, Precocious; Gastrointestinal Microbiome; Gonadal Steroid Hormones; Puberty; Microbiota
PubMed: 36339428
DOI: 10.3389/fendo.2022.1000919 -
Cell Stem Cell Feb 2020The human testis undergoes dramatic developmental and structural changes during puberty, including proliferation and maturation of somatic niche cells, and the onset of...
The human testis undergoes dramatic developmental and structural changes during puberty, including proliferation and maturation of somatic niche cells, and the onset of spermatogenesis. To characterize this understudied process, we profiled and analyzed single-cell transcriptomes of ∼10,000 testicular cells from four boys spanning puberty and compared them to those of infants and adults. During puberty, undifferentiated spermatogonia sequentially expand and differentiate prior to the initiation of gametogenesis. Notably, we identify a common pre-pubertal progenitor for Leydig and myoid cells and delineate candidate factors controlling pubertal differentiation. Furthermore, pre-pubertal Sertoli cells exhibit two distinct transcriptional states differing in metabolic profiles before converging to an alternative single mature population during puberty. Roles for testosterone in Sertoli cell maturation, antimicrobial peptide secretion, and spermatogonial differentiation are further highlighted through single-cell analysis of testosterone-suppressed transfemale testes. Taken together, our transcriptional atlas of the developing human testis provides multiple insights into developmental changes and key factors accompanying male puberty.
Topics: Adult; Humans; Infant; Male; Puberty; Sertoli Cells; Spermatogenesis; Spermatogonia; Testis
PubMed: 31928944
DOI: 10.1016/j.stem.2019.12.005 -
The Lancet. Diabetes & Endocrinology Mar 2023Puberty is a major maturational event; its mechanisms and timing are driven by genetic determinants, but also controlled by endogenous and environmental cues.... (Review)
Review
Puberty is a major maturational event; its mechanisms and timing are driven by genetic determinants, but also controlled by endogenous and environmental cues. Substantial progress towards elucidation of the neuroendocrine networks governing puberty has taken place. However, key aspects of the mechanisms responsible for the precise timing of puberty and its alterations have only recently begun to be deciphered, propelled by epidemiological data suggesting that pubertal timing is changing in humans, via mechanisms that are not yet understood. By integrating basic and clinical data, we provide a comprehensive overview of current advances on the physiological basis of puberty, with a particular focus on the roles of kisspeptins and other central transmitters, the underlying molecular and endocrine mechanisms, and the pathways involved in pubertal modulation by nutritional and metabolic cues. Additionally, we have summarised molecular features of precocious and delayed puberty in both sexes, as revealed by clinical and genetic studies. This Review is a synoptic up-to-date view of how puberty is controlled and of the pathogenesis of major pubertal alterations, from both a clinical and translational perspective. We also highlight unsolved challenges that will seemingly concentrate future research efforts in this active domain of endocrinology.
Topics: Male; Female; Humans; Puberty; Kisspeptins; Puberty, Precocious
PubMed: 36620967
DOI: 10.1016/S2213-8587(22)00339-4 -
Frontiers in Endocrinology 2022Gonadotrophin dependent sexual precocity, commonly referred to as central precocious puberty (CPP), results from a premature reactivation of the... (Review)
Review
Gonadotrophin dependent sexual precocity, commonly referred to as central precocious puberty (CPP), results from a premature reactivation of the hypothalamic-pituitary-gonadal (HPG) axis before the normal age of pubertal onset. CPP is historically described as girls who enter puberty before the age of eight, and boys before the age of nine. Females are more likely to be diagnosed with idiopathic CPP; males diagnosed with CPP have a greater likelihood of a defined etiology. These etiologies may include underlying CNS congenital defects, tumors, trauma, or infections as well as environmental, genetic, and epigenetic factors. Recently, genetic variants and mutations which may cause CPP have been identified at both the level of the hypothalamus and the pituitary. Single nucleotide polymorphisms (SNPs), monogenetic mutations, and modifications of the epigenome have been evaluated in relationship to the onset of puberty; these variants are thought to affect the development, structure and function of GnRH neurons which may lead to either precocious, delayed, or absent pubertal reactivation. This review will describe recent advances in the field of the genetic basis of puberty and provide a clinically relevant approach to better understand these varying etiologies of CPP.
Topics: Humans; Male; Female; Puberty, Precocious; Gonadotropin-Releasing Hormone; Epigenesis, Genetic; Puberty; Epigenomics
PubMed: 36531492
DOI: 10.3389/fendo.2022.1029137 -
Italian Journal of Pediatrics Mar 2022Constitutional delay of growth and puberty (CDGP) is classified as the most frequent cause of delayed puberty (DP). Finding out the etiology of DP during first... (Review)
Review
BACKGROUND
Constitutional delay of growth and puberty (CDGP) is classified as the most frequent cause of delayed puberty (DP). Finding out the etiology of DP during first evaluation may be a challenge. In details, pediatricians often cannot differentiate CDGP from permanent hypogonadotropic hypogonadism (PHH), with definitive diagnosis of PHH awaiting lack of puberty by age 18 yr. Neverthless, the ability in providing a precise and tempestive diagnosis has important clinical consequences.
MAIN TEXT
A growth failure in adolescents with CDGP may occur until the onset of puberty; after that the growth rate increases with rapidity. Bone age is typically delayed. CDGP is generally a diagnosis of exclusion. Nevertheless, other causes of DP must be evaluated. A family history including timing of puberty in the mother and in the father as well as physical examination may givee information on the cause of DP. Patients with transient delay in hypothalamic-pituitary-gonadal axis maturation due to associated conditions, such as celiac disease, inflammatory bowel diseases, kidney insufficiency and anorexia nervosa, may experience a functional hypogonadotropic hypogonadism. PHH revealing testosterone or estradiol low serum values and reduced FSH and LH levels may be connected to abnormalities in the central nervous system. So, magnetic resonance imaging is required in order to exclude either morphological alterations or neoplasia. If the adolescent with CDGP meets psychological difficulties, treatment is recommended.
CONCLUSION
Even if CDGP is considered a variant of normal growth rather than a disease, short stature and retarded sexual development may led to psychological problems, sometimes associated to a poor academic performance. A prompt and precise diagnosis has an important clinical outcome. Aim of this mini-review is throwing light on management of patients with CDGP, emphasizing the adolescent diagnosis and trying to answer all questions from paediatricians.
Topics: Adolescent; Female; Growth Disorders; Humans; Hypogonadism; Klinefelter Syndrome; Puberty; Puberty, Delayed
PubMed: 35331309
DOI: 10.1186/s13052-022-01242-5 -
Clinical Endocrinology Oct 2021Central precocious puberty (CPP) results from early activation of the hypothalamic-pituitary-gonadal (HPG) axis. The current state of knowledge of the complex neural... (Review)
Review
Central precocious puberty (CPP) results from early activation of the hypothalamic-pituitary-gonadal (HPG) axis. The current state of knowledge of the complex neural network acting at the level of the hypothalamus and the GnRH neuron to control puberty onset has expanded, particularly in the context of molecular interactions. Along with these advances, the knowledge of pubertal physiology and pathophysiology has also increased. This review focuses on regulatory abnormalities occurring at the hypothalamic level of the HPG axis to cause CPP. The clinical approach to diagnosis of puberty and pubertal disorders is also reviewed, with a particular focus on aetiologies of CPP. The recent identification of mutations in MKRN3 and DLK1 in familial as well sporadic forms of CPP has changed the state of the art of the approach to patients with CPP. Genetic advances have also had important repercussions beyond consideration of puberty alone. Syndromic disorders and central nervous system lesions associated with CPP are also discussed. If untreated, these conditions may lead to adverse physical, psychosocial and medical outcomes.
Topics: Gonadotropin-Releasing Hormone; Humans; Mutation; Puberty; Puberty, Precocious; Ubiquitin-Protein Ligases
PubMed: 33797780
DOI: 10.1111/cen.14475