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Neuroendocrinology 2014All reproductively competent adults have gone through puberty. While key genes and signaling pathways that lead to the onset of sexual maturation are known, the... (Review)
Review
All reproductively competent adults have gone through puberty. While key genes and signaling pathways that lead to the onset of sexual maturation are known, the molecular mechanisms that determine when an individual enters puberty are only beginning to be understood. Both genetic and environmental factors determine the timing of puberty. New advances in understanding how environmentally sensitive, yet highly heritable developmental processes are regulated have come from the field of epigenetics. Of note, studies investigating the epigenetic control of the onset of puberty suggest that epigenetic repression of key inhibitory loci may play a fundamental role in the initiation of puberty. Current technologies that not only read out the DNA sequence, but also determine how the DNA is modified in response to the environment, promise new insight into how puberty is regulated, including the identification and understanding of gene regulatory networks that control the biological pathways affecting pubertal timing. Here we review the findings to date and discuss how epigenetic investigation can further our understanding of this fundamental aspect of human development.
Topics: Animals; Epigenesis, Genetic; Epigenomics; Humans; Puberty; Sexual Maturation
PubMed: 24718029
DOI: 10.1159/000362559 -
Nutrients Jan 2021Puberty is a crucial developmental stage in the life span, necessary to achieve reproductive and somatic maturity. Timing of puberty is modulated by and responds to... (Review)
Review
Puberty is a crucial developmental stage in the life span, necessary to achieve reproductive and somatic maturity. Timing of puberty is modulated by and responds to central neurotransmitters, hormones, and environmental factors leading to hypothalamic-pituitary-gonadal axis maturation. The connection between hormones and nutrition during critical periods of growth, like fetal life or infancy, is fundamental for metabolic adaptation response and pubertal development control and prediction. Since birth weight is an important indicator of growth estimation during fetal life, restricted prenatal growth, such as intrauterine growth restriction (IUGR) and small for gestational age (SGA), may impact endocrine system, affecting pubertal development. Successively, lactation along with early life optimal nutrition during infancy and childhood may be important in order to set up timing of sexual maturation and provide successful reproduction at a later time. Sexual maturation and healthy growth are also influenced by nutrition requirements and diet composition. Early nutritional surveillance and monitoring of pubertal development is recommended in all children, particularly in those at risk, such as the ones born SGA and/or IUGR, as well as in the case of sudden weight gain during infancy. Adequate macro and micronutrient intake is essential for healthy growth and sexual maturity.
Topics: Child; Child Nutritional Physiological Phenomena; Fetus; Humans; Infant; Nutritional Status; Puberty; Sexual Maturation; Time Factors
PubMed: 33525559
DOI: 10.3390/nu13020419 -
American Journal of Physiology. Renal... Oct 2002Puberty accelerates microvascular complications of diabetes mellitus, including nephropathy. Animal studies confirm a different renal hypertrophic response to diabetes... (Review)
Review
Puberty accelerates microvascular complications of diabetes mellitus, including nephropathy. Animal studies confirm a different renal hypertrophic response to diabetes before and after puberty, probably due to differences in the production of transforming growth factor-beta (TGF-beta). Many of the complex physiological changes during puberty could affect potentially pathogenic mechanisms of diabetic kidney disease. Increased blood pressure, activation of the growth hormone-insulin-like growth factor I axis, and production of sex steroids could all play a role in pubertal susceptibility to diabetic renal hypertrophy and nephropathy. These factors may influence the effects of hyperglycemia and several systems that ultimately control TGF-beta production, including the renin-angiotensin system, cellular redox systems, the polyol pathway, and protein kinase C. These phenomena may also explain gender differences in kidney function and incidence of end-stage renal disease. Normal changes during puberty, when coupled with diabetes and superimposed on a genetically susceptible milieu, are capable of accelerating diabetic hypertrophy and microvascular lesions. A better understanding of these processes may lead to new treatments to prevent renal failure in diabetes mellitus.
Topics: Adolescent; Diabetic Nephropathies; Female; Gonadal Steroid Hormones; Humans; Kidney; Male; Puberty
PubMed: 12217849
DOI: 10.1152/ajprenal.00368.2001 -
Reproduction (Cambridge, England) Mar 2014Kisspeptin is vital for the neuroendocrine regulation of GNRH secretion. Kisspeptin neurons are now recognized as a central pathway responsible for conveying key... (Review)
Review
Kisspeptin is vital for the neuroendocrine regulation of GNRH secretion. Kisspeptin neurons are now recognized as a central pathway responsible for conveying key homeostatic information to GNRH neurons. This pathway is likely to mediate the well-established link between energy balance and reproductive function. Thus, in states of severely altered energy balance (either negative or positive), fertility is compromised, as is Kiss1 expression in the arcuate nucleus. A number of metabolic modulators have been proposed as regulators of kisspeptin neurons including leptin, ghrelin, pro-opiomelanocortin (POMC), and neuropeptide Y (NPY). Whether these regulate kisspeptin neurons directly or indirectly will be discussed. Moreover, whether the stimulatory role of leptin on reproduction is mediated by kisspeptin directly will be questioned. Furthermore, in addition to being expressed in GNRH neurons, the kisspeptin receptor (Kiss1r) is also expressed in other areas of the brain, as well as in the periphery, suggesting alternative roles for kisspeptin signaling outside of reproduction. Interestingly, kisspeptin neurons are anatomically linked to, and can directly excite, anorexigenic POMC neurons and indirectly inhibit orexigenic NPY neurons. Thus, kisspeptin may have a direct role in regulating energy balance. Although data from Kiss1r knockout and WT mice found no differences in body weight, recent data indicate that kisspeptin may still play a role in food intake and glucose homeostasis. Thus, in addition to regulating reproduction, and mediating the effect of energy balance on reproductive function, kisspeptin signaling may also be a direct regulator of metabolism.
Topics: Animals; Energy Metabolism; Fertility; Homeostasis; Humans; Kisspeptins; Mice; Puberty; Reproduction; Sexual Maturation
PubMed: 24327738
DOI: 10.1530/REP-13-0509 -
International Journal of Epidemiology Jun 2020Early puberty is a risk indicator for adult diseases. Identification of modifiable causes of earlier puberty is, therefore, warranted. We estimate the association...
BACKGROUND
Early puberty is a risk indicator for adult diseases. Identification of modifiable causes of earlier puberty is, therefore, warranted. We estimate the association between childhood body mass index (BMI) and pubertal timing in a cohort study and in a sibling-matched study to adjust for unobserved time-stable confounders shared within families.
METHODS
For the cohort study, 11 046 of 22 439 (49%) invited children, born 2000-203, from the Danish National Birth Cohort (DNBC) had information on childhood BMI at 7 years and self-reported, half-yearly puberty information from 11 years on Tanner stages, menarche, voice break, first ejaculation, acne, and axillary hair. For the sibling-matched study, 1700 brothers and sisters were included among 86 820 live-born singletons from the DNBC.
RESULTS
Childhood overweight (85th ≤ BMI < 95th percentile) and obesity (BMI ≥ 95th percentile) were associated with earlier age attaining the pubertal milestones in a dose-dependent manner in boys and girls. When modelling all pubertal milestones simultaneously, the pubertal milestones were attained earlier in: overweight boys: -3.1 [95% confidence interval (CI): -4.5, -1.7] months, overweight girls: -5.5 (95% CI: -7.1, -3.9) months, obese boys: -3.5 (95% CI: -5.1, -2.0) months, obese girls: -5.2 (95% CI: -7.1, -3.4) months compared with normal weight (BMI < 85th percentile) children. In the sibling-matched study, higher BMI was associated with earlier age at attaining most pubertal milestones in girls, but only a tendency toward earlier pubertal timing was observed in boys.
CONCLUSIONS
Childhood overweight and obesity were associated with earlier pubertal timing even after adjustment for unobserved time-stable confounders shared within families.
Topics: Child; Cohort Studies; Denmark; Female; Humans; Male; Pediatric Obesity; Puberty; Siblings; Time Factors
PubMed: 32372073
DOI: 10.1093/ije/dyaa056 -
The Journal of Endocrinology Aug 2019Puberty is driven by sophisticated neuroendocrine networks that timely activate the brain centers governing the reproductive axis. The timing of puberty is genetically... (Review)
Review
Puberty is driven by sophisticated neuroendocrine networks that timely activate the brain centers governing the reproductive axis. The timing of puberty is genetically determined; yet, puberty is also sensitive to numerous internal and external cues, among which metabolic/nutritional signals are especially prominent. Compelling epidemiological evidence suggests that alterations of the age of puberty are becoming more frequent; the underlying mechanisms remain largely unknown, but the escalating prevalence of obesity and other metabolic/feeding disorders is possibly a major contributing factor. This phenomenon may have clinical implications, since alterations in pubertal timing have been associated to adverse health outcomes, including higher risk of earlier all-cause mortality. This urges for a better understanding of the neurohormonal basis of normal puberty and its deviations. Compelling evidence has recently documented the master role of hypothalamic neurons producing kisspeptins, encoded by Kiss1, in the neuroendocrine pathways controlling puberty. Kiss1 neurons seemingly participate in transmitting the regulatory actions of metabolic cues on pubertal maturation. Key cellular metabolic sensors, as the mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK) and the fuel-sensing deacetylase, SIRT1, have been recently shown to participate also in the metabolic modulation of puberty. Recently, we have documented that AMPK and SIRT1 operate as major molecular effectors for the metabolic control of Kiss1 neurons and, thereby, puberty onset. Alterations of these molecular pathways may contribute to the perturbation of pubertal timing linked to conditions of metabolic stress in humans, such as subnutrition or obesity and might become druggable targets for better management of pubertal disorders.
Topics: Animals; Energy Metabolism; Female; Humans; Hypothalamus; Malnutrition; Neurosecretory Systems; Obesity; Puberty; Sexual Maturation
PubMed: 31189134
DOI: 10.1530/JOE-19-0223 -
Human Brain Mapping Jun 2010Adolescence refers to the period of physical and psychological development between childhood and adulthood. The beginning of adolescence is loosely anchored to the onset... (Review)
Review
Adolescence refers to the period of physical and psychological development between childhood and adulthood. The beginning of adolescence is loosely anchored to the onset of puberty, which brings dramatic alterations in hormone levels and a number of consequent physical changes. Puberty onset is also associated with profound changes in drives, motivations, psychology, and social life; these changes continue throughout adolescence. There is an increasing number of neuroimaging studies looking at the development of the brain, both structurally and functionally, during adolescence. Almost all of these studies have defined development by chronological age, which shows a strong-but not unitary-correlation with pubertal stage. Very few neuroimaging studies have associated brain development with pubertal stage, and yet there is tentative evidence to suggest that puberty might play an important role in some aspects of brain and cognitive development. In this paper we describe this research, and we suggest that, in the future, developmental neuroimaging studies of adolescence should consider the role of puberty.
Topics: Adolescent; Animals; Brain; Cognition; Hormones; Humans; Magnetic Resonance Imaging; Puberty; Sexual Maturation
PubMed: 20496383
DOI: 10.1002/hbm.21052 -
Hormone Research Jan 2009Insulin is well known for its effects on carbohydrate metabolism, but this hormone also plays an important role in regulating ovarian function. Granulosa, theca and... (Review)
Review
Insulin is well known for its effects on carbohydrate metabolism, but this hormone also plays an important role in regulating ovarian function. Granulosa, theca and stromal ovarian cells may be affected by insulin deficiency or excess, which may be present in women with type 1 diabetes mellitus (T1D). Recent publications have shown that in spite of intensive insulin therapy, some delay in the age of thelarche, pubarche and menarche is still observed in girls with T1D. In addition, ovarian hyperandrogenism may be observed during late adolescence and an increased prevalence of hirsutism and polycystic ovarian syndrome (PCOS) has been described in adult women with T1D. These endocrine abnormalities may be related to nonphysiologic insulin replacement therapy and to hyperglycemia. This paper reviews the pubertal development and the clinical reproductive abnormalities observed in girls with type 1 diabetes mellitus, and shows that several significant clinical problems, such as pubertal delay, menstrual disturbances and hyperandrogenism which may ultimately lead to the development of PCOS in adulthood, may be observed in some of these patients.
Topics: Adolescent; Animals; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Insulin Resistance; Menarche; Ovary; Puberty
PubMed: 19039232
DOI: 10.1159/000173737 -
Environmental Health Perspectives Apr 2000The effects of toxicants depend on the dose and the time in the life span when exposure occurs. The biology of adolescence is distinctive and provides opportunities for... (Review)
Review
The effects of toxicants depend on the dose and the time in the life span when exposure occurs. The biology of adolescence is distinctive and provides opportunities for unique actions of toxicants both in terms of disruption of function and disruption of maturation. Maturation of a number of organ systems occurs during this period, including not only the reproductive system but also the respiratory, skeletal, immune, and central nervous systems. Adolescence is a time of increased risk for infectious disease and accidental injury, making the effects of toxicants on the immune and central nervous systems particularly harmful. Differences in blood volume, respiratory parameters, metabolic needs, and capacity all contribute to altered pharmacokinetics. Exposures can also change. Increased food intake associated with rapid adolescent growth alters exposure to food contaminants. Voluntary drug consumption increases, including drinking; smoking; substance abuse; and the use of over-the-counter, prescription, and performance-enhancing drugs. At the same time, adolescents are introduced to toxicants in the workplace. Basic research in the toxicology of adolescence needs to take into account the appropriateness of animal models for this distinctive human developmental stage; risk assessment must take into account pharmacokinetic and lifestyle factors. Screening methodologies that would identify toxic effects unique to adolescence would also be valuable.
Topics: Adolescent; Animals; Disease Models, Animal; Environmental Health; Female; Humans; Life Style; Male; Puberty; Substance-Related Disorders; Xenobiotics
PubMed: 10753095
DOI: 10.1289/ehp.00108355 -
Missouri Medicine 2015Sleep in women differs in many respects from that of men. In general, women appear to report a greater need for sleep and more subjective complaints of non-refreshing... (Review)
Review
Sleep in women differs in many respects from that of men. In general, women appear to report a greater need for sleep and more subjective complaints of non-refreshing sleep than men. Sleep in women is affected at least partially by hormonal factors, with women typically suffering from sleep disturbance in connection with the menstrual cycle, pregnancy, and menopause Menstrual cycles are associated with prominent changes in reproductive hormones that may influence sleep. Sleep apnea and restless legs syndrome may be aggravated by pregnancy. Women may also develop insomnia during pregnancy, childbirth and menopause.
Topics: Female; Humans; Male; Menopause; Menstrual Cycle; Pregnancy; Puberty; Sleep; Women's Health
PubMed: 26821442
DOI: No ID Found