-
Nature Nov 2021The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development....
The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development. The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure. Here we present evidence that MC3R regulates the timing of sexual maturation, the rate of linear growth and the accrual of lean mass, which are all energy-sensitive processes. We found that humans who carry loss-of-function mutations in MC3R, including a rare homozygote individual, have a later onset of puberty. Consistent with previous findings in mice, they also had reduced linear growth, lean mass and circulating levels of IGF1. Mice lacking Mc3r had delayed sexual maturation and an insensitivity of reproductive cycle length to nutritional perturbation. The expression of Mc3r is enriched in hypothalamic neurons that control reproduction and growth, and expression increases during postnatal development in a manner that is consistent with a role in the regulation of sexual maturation. These findings suggest a bifurcating model of nutrient sensing by the central melanocortin pathway with signalling through MC4R controlling the acquisition and retention of calories, whereas signalling through MC3R primarily regulates the disposition of calories into growth, lean mass and the timing of sexual maturation.
Topics: Adolescent; Aged, 80 and over; Animals; Child; Child Development; Estrous Cycle; Female; Homozygote; Humans; Hypothalamus; Insulin-Like Growth Factor I; Male; Melanocortins; Menarche; Mice; Nutritional Status; Phenotype; Puberty; Receptor, Melanocortin, Type 3; Sexual Maturation; Time Factors; Weight Gain
PubMed: 34732894
DOI: 10.1038/s41586-021-04088-9 -
Seminars in Reproductive Medicine Mar 2022Puberty is the process through which reproductive competence is achieved and comprises gonadarche and adrenarche. Breast development is the initial physical finding of... (Review)
Review
Puberty is the process through which reproductive competence is achieved and comprises gonadarche and adrenarche. Breast development is the initial physical finding of pubertal onset in girls and typically occurs between 8 and 13 years. Menarche normally occurs 2 to 3 years after the onset of breast development. Pubertal onset is controlled by the gonadotropin-releasing hormone pulse generator in the hypothalamus; however, environmental factors such as alterations in energy balance and exposure to endocrine-disrupting chemicals can alter the timing of pubertal onset. Improvement in nutritional and socioeconomic conditions over the past two centuries has been associated with a secular trend in earlier pubertal onset. Precocious puberty is defined as onset of breast development prior to 8 years and can be central or peripheral. Delayed puberty can be hypogonadotropic or hypergonadotropic and is defined as lack of breast development by 13 years or lack of menarche by 16 years. Both precocious and delayed puberty may have negative effects on self-esteem, potentially leading to psychosocial stress. Patients who present with pubertal differences require a comprehensive assessment to determine the underlying etiology and to devise an effective treatment plan.
Topics: Female; Gonadotropin-Releasing Hormone; Humans; Menarche; Puberty; Puberty, Delayed; Puberty, Precocious
PubMed: 34560809
DOI: 10.1055/s-0041-1735892 -
Journal of Cystic Fibrosis : Official... Oct 2019Historically, delayed puberty was considered a common clinical feature of cystic fibrosis (CF). More recent reports have documented normal pubertal progression in the... (Review)
Review
Historically, delayed puberty was considered a common clinical feature of cystic fibrosis (CF). More recent reports have documented normal pubertal progression in the majority of individuals with CF. However, youth with more severe disease are still at risk for delayed puberty. Careful evaluation of pubertal development in children and adolescents with CF is important as pubertal timing impacts linear growth, bone mineral accrual, body image and psychosocial wellbeing, all of which can also be impacted directly by CF. This article reviews the physiology of puberty, timing of puberty in CF, evaluation of pubertal development, and the differential diagnosis, evaluation, and management of delayed and precocious puberty in people with CF.
Topics: Adolescent; Child; Cystic Fibrosis; Diagnosis, Differential; Female; Humans; Male; Puberty; Puberty, Delayed
PubMed: 31679734
DOI: 10.1016/j.jcf.2019.08.013 -
Best Practice & Research. Clinical... Jan 2022Puberty marks the end of childhood and is a period when individuals undergo physiological and psychological changes to achieve sexual maturation and fertility. The onset... (Review)
Review
Puberty marks the end of childhood and is a period when individuals undergo physiological and psychological changes to achieve sexual maturation and fertility. The onset of puberty is first detected as an increase in pulsatile secretion of gonadotropin-releasing hormone (GnRH). Pubertal onset is regulated by genetic, nutritional, environmental, and socio-economic factors. Disturbances affecting pubertal timing result in adverse health conditions later in life. Human genetic studies show that around 50-80% of the variation in pubertal onset is genetically determined. The genetic control of pubertal timing has been a field of active investigation in attempt to better understand the neuroendocrine control of this relevant period of life. Large populational studies and patient cohort-based studies have provided insights into the genetic regulation of pubertal onset. In this review, we discuss these discoveries and discuss potential mechanisms for how implicated genes may affect pubertal timing.
Topics: Gonadotropin-Releasing Hormone; Humans; Puberty; Puberty, Delayed; Sexual Maturation
PubMed: 35183440
DOI: 10.1016/j.beem.2022.101618 -
Pediatrics in Review Sep 2022
Topics: Humans; Puberty; Puberty, Precocious
PubMed: 36045159
DOI: 10.1542/pir.2021-005059 -
Pediatrics in Review Aug 2022
Topics: Diagnosis, Differential; Humans; Puberty; Puberty, Delayed
PubMed: 35909138
DOI: 10.1542/pir.2020-005291 -
Current Opinion in Pediatrics Aug 2020Adrenarche is the pubertal maturation of the innermost zone of the adrenal cortex, the zona reticularis. The onset of adrenarche occurs between 6 and 8 years of age when... (Review)
Review
PURPOSE OF REVIEW
Adrenarche is the pubertal maturation of the innermost zone of the adrenal cortex, the zona reticularis. The onset of adrenarche occurs between 6 and 8 years of age when dehydroepiandrosterone sulfate (DHEAS) concentrations increase. This review provides an update on adrenal steroidogenesis and the differential diagnosis of premature development of pubic hair.
RECENT FINDINGS
The complexity of adrenal steroidogenesis has increased with recognition of the alternative 'backdoor pathway' and the 11-oxo-androgens pathways. Traditionally, sulfated steroids such as DHEAS have been considered to be inactive metabolites. Recent data suggest that intracellular sulfated steroids may function as tissue-specific intracrine hormones particularly in the tissues expressing steroid sulfatases such as ovaries, testes, and placenta.
SUMMARY
The physiologic mechanisms governing the onset of adrenarche remain unclear. To date, no validated regulatory feedback mechanism has been identified for adrenal C19 steroid secretion. Available data indicate that for most children, premature adrenarche is a benign variation of development and a diagnosis of exclusion. Patients with premature adrenarche tend to have higher BMI values. Yet, despite greater knowledge about C19 steroids and zona reticularis function, much remains to be learned about adrenarche.
Topics: Adrenal Glands; Adrenarche; Androgens; Child; Child Development; Dehydroepiandrosterone Sulfate; Female; Humans; Pregnancy; Puberty; Puberty, Precocious; Steroids; Zona Reticularis
PubMed: 32692055
DOI: 10.1097/MOP.0000000000000928 -
Obesity Reviews : An Official Journal... Jun 2020In this review, we discuss the role of adipokines in the onset of puberty in children with obesity during adrenarche and gonadarche and provide a clear and detailed... (Review)
Review
In this review, we discuss the role of adipokines in the onset of puberty in children with obesity during adrenarche and gonadarche and provide a clear and detailed overview of the biological processes of two major players, leptin and adiponectin. Adipokines, especially leptin and adiponectin, seem to induce an early onset of puberty in girls and boys with obesity by affecting the hypothalamic-pituitary-gonadal (HPG) axis. Moreover, adipokines and their receptors are expressed in the gonads, suggesting a role in sexual maturation and reproduction. All in all, adipokines may be a clue in understanding mechanisms underlying the onset of puberty in childhood obesity and puberty onset variability.
Topics: Adipokines; Adolescent; Child; Female; Humans; Male; Pediatric Obesity; Puberty
PubMed: 32003144
DOI: 10.1111/obr.13005 -
Molecular Reproduction and Development May 2020Lin28a and Lin28b, homologs of the Caenorhabditis elegans Lin28 gene, play important roles in cell pluripotency, reprogramming, and tumorigenicity. Recently, genome-wide... (Review)
Review
Lin28a and Lin28b, homologs of the Caenorhabditis elegans Lin28 gene, play important roles in cell pluripotency, reprogramming, and tumorigenicity. Recently, genome-wide association and transgenic studies showed that Lin28a and/or Lin28b gene were involved in the onset of mammalian puberty, the stage representing the attainment of reproduction capacity; however, the detailed mechanism of these genes in mammalian puberty remains largely unknown. The present paper reviews the research progress on the roles of Lin28a/b genes in the onset of mammalian puberty by analyzing the results coming from gene expression patterns, mutations, and transgenic studies, and put forward possible pathways for further studies on their roles in animal reproduction.
Topics: Animals; Animals, Genetically Modified; Female; Genome-Wide Association Study; Humans; Male; Mammals; Puberty; RNA-Binding Proteins; Sexual Maturation
PubMed: 32363678
DOI: 10.1002/mrd.23347 -
Reproduction (Cambridge, England) Feb 2023Sex differences in the gut microbiome may impact multiple aspects of human health and disease. In this study, we review the evidence for microbial sex differences in... (Review)
Review
IN BRIEF
Sex differences in the gut microbiome may impact multiple aspects of human health and disease. In this study, we review the evidence for microbial sex differences in puberty and adulthood and discuss potential mechanisms driving differentiation of the sex-specific gut microbiome.
ABSTRACT
In humans, the gut microbiome is strongly implicated in numerous sex-specific physiological processes and diseases. Given this, it is important to understand how sex differentiation of the gut microbiome occurs and how these differences contribute to host health and disease. While it is commonly believed that the gut microbiome stabilizes after 3 years of age, our review of the literature found considerable evidence that the gut microbiome continues to mature during and after puberty in a sex-dependent manner. We also review the intriguing, though sparse, literature on potential mechanisms by which host sex may influence the gut microbiome, and vice versa, via sex steroids, bile acids, and the immune system. We conclude that the evidence for the existence of a sex-specific gut microbiome is strong but that there is a dearth of research on how host-microbe interactions lead to this differentiation. Finally, we discuss the types of future studies needed to understand the processes driving the maturation of sex-specific microbial communities and the interplay between gut microbiota, host sex, and human health.
Topics: Female; Humans; Male; Adult; Gastrointestinal Microbiome; Bile Acids and Salts; Puberty
PubMed: 36445259
DOI: 10.1530/REP-22-0303