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Publicado por Pulso ediciones, S. Todos los derechos reservados. Tendencia secular, pubertad normal Correspondencia: The intimate phenomenon that favors the onset Pubertad precoz isosexual definicion puberty is the increase in the number and amplitude of gonadotropin-releasing hormone secretion peaks GnRH by hypothalamic GnRH-producing neurons which in turn is regulated by a complex network of genes that encodes proteins capable of producing transynaptic changes that may act
Pubertad precoz isosexual definicion kisspeptin or inhibiting MKRN3 GnRH synthesis.
In spite of the Pubertad precoz isosexual definicion trend of decreasing age of onset of puberty showed between the nineteenth century and the mid-twentieth century, it seems that in the last 3 decades it has been seen some stabilization in a way that is considered normal pubertal development that will take place between Pubertad precoz isosexual definicion and 13 years in girls and between 9 and 14 years in children.
Estas interacciones se inician en etapas tempranas del desarrollo, por lo que la pubertad debe considerarse la parte final de un proceso madurativo complejo regulado por las interacciones de genes y ambiente.
Seguidamente, de forma progresiva, se desarrollan el resto de
Pubertad precoz isosexual definicion sexuales secundarios. Asimismo, durante el periodo puberal se objetiva un incremento de velocidad de crecimiento.
Retraso constitucional del crecimiento y pubertad: No obstante, en este grupo se incluye variante de la normalidad: The timing of normal puberty and the age
Pubertad precoz isosexual definicion of sexual precocity: Endocr Rev ; Pubertad precoz isosexual definicion SR. Desarrollo sexual y Pubertad.
Pubertad normal y sus variantes En: Pubertad normal y variantes de la normalidad.
Pubertad precoz isosexual definicion networks and the neuroendocrine regulation of puberty. Mol Cell Endocrinol ; Epigenetic regulation of female puberty.
Front Neuroendocrinol ; 36C: Lomniczi A,
Pubertad precoz isosexual definicion SR. The emerging role of epigenetics in the regulation of female puberty. Endocr Dev ; Link between body fat and the timing of puberty. Metabolic signals in human puberty: Recent secular trends in pubertal timing: Horm Res Paediatr ; 77 3: Variations in the pattern of pubertal changes in girls.
Arch Dis Child ; Variations in the pattern of pubertal changes
Pubertad precoz isosexual definicion boys.
Secondary sexual characteristics and menses in young girls seen in office practice: N Engl J Med ; Causes, diagnosis, and treatment of central precocious puberty. Lancet Diabetes Endocrinol ; 4 3: Editorial Mc Graw Hill, 2nd Edition, ; p. From a neurobiological perspective, this process is incumbent to the timed activation of the population of hypothalamic neurons producing gonadotropin-releasing hormone GnRH ; the enhancement of GnRH neurosecretory activity being ultimately responsible for the triggering of puberty.
In the last decade, kisspeptins have emerged as pivotal upstream regulators of GnRH neurons, with prominent roles in their activation during the pubertal transition and its direct or indirect Pubertad precoz isosexual definicion by different regulatory signals, including metabolic cues. We will briefly review herein the major features of kisspeptins and their producing neurons, the socalled Kiss1 neurons, as major gatekeepers and fine regulators of reproductive maturation and puberty onset in mammals.
Introduction Puberty is major event in the lifespan of Pubertad precoz isosexual definicion individual, which culminates with the attainment of sexual somatic, psychological maturity and reproductive capacity 1. This intricate maturational phenomenon is grounded on early differentiation events starting in uteroand involves a complex series morphological, functional, Correspondencia: Accordingly, puberty is regarded not only as a specific, relatively narrow stage of development, but rather considered as the final output of a maturational continuum that leads to Pubertad precoz isosexual definicion competence.
The tempo of puberty is dictated by the dynamic interplay between genetic environmental factors 1so that perturbation of such dialogue often results in the
Pubertad precoz isosexual definicion development of the reproductive axis that commonly leads to alterations of the timing of puberty precocious, delayed or absent.
In this sense, beyond its paramount biological relevance, puberty may be considered as putative sentinel for perturbations of the gene-environment interactions along early stages of development, whose alterations may lead to deregulation of key homeostatic systems. In fact, changes in the timing of puberty, especially earlier puberty, might impact important development events, including somatic and psychological maturation, and appear to be linked to numerous adverse health outcomes 2as well as reduced life expectancy Pubertad precoz isosexual definicion. This is specially worrying given the reported trends for changes in the age of puberty mostly earlierwhich seem to be more frequent in girls but appear to occur also in boys These observations urge for a better understanding of the physiological control of puberty, and of the pathophysiological basis of its alterations.
This neurohormonal system primarily in- 8.
In addition, the HPG axis Pubertad precoz isosexual definicion also modulated by other endogenous factors, e. From its reproductive perspective, the initiation of puberty is founded on the heightening of the pulsatile release of hypothalamic GnRH 9. Yet, the intimate whereby this increase Pubertad precoz isosexual definicion remain ill defined. The current view, articulated in the so-called central drive hypothesis, concurs that the increase in the pulsatile GnRH secretion leading
Pubertad precoz isosexual definicion the onset of puberty is the result of changes in the activity of the Pubertad precoz isosexual definicion pathways controlling GnRH neurons, with a switch in the balance between excitatory inputs which increase and inhibitory signals which decrease at the time of pubertythus causing the drive for the pubertal activation of the HPG axis 9.
Notably, the activator afferents of GnRH neurons include not only transsynaptic inputs but also glial-born factors Kisspeptins and the central control of puberty While the control of GnRH neurons is multifactorial, and Pubertad precoz isosexual definicion neuropeptides and transmitters have been shown in the last decades to regulate GnRH secretion, kisspeptins have emerged in recent years as fundamental regulatory signals, with an essential role in the control of puberty Kisspeptins are a family of structurally related peptides, encoded by the Kiss1
Pubertad precoz isosexual definicion, which act via the G protein-coupled receptor, Gpr54, also termed Kiss1R or kisspeptin receptor 11, Pubertad precoz isosexual definicion reproductive facet of kisspeptins, and their role in the precise control of puberty, was surfaced by seminal observations, back inthat inactivating mutations of GPR54 were linked to absence of puberty and hypogonadism of central origin aka, hypogonadotropic hypogonadism in humans 13, Such reproductive role was further demonstrated by the observation of similar phenotypes in patients with inactivating mutations of KISS1 and null mice for Gpr54 or Kiss1 These findings boosted enormous interest and prompted the analysis of the physiological roles of Kiss1 neurons in the regulation of GnRH neurosecretion and puberty onset.
While detailed recapitulation of the results of these studies clearly exceeds the scope of this review, it is important to stress that such analyses have unambiguously documented a sophisticated developmental program of Kiss1 neurons, responsible for their activation during the pubertal maturation 11, This complex and multifaceted phenomenon includes, at least, the following major components: In good agreement, pharmacological blockade of kisspeptin signaling has been reported to delay the onset of puberty in female rats 25whereas ablation of Kiss1 neurons in the juvenile period prevented pubertal Pubertad precoz isosexual definicion in female mice Despite the solid clinical and experimental evidence suggesting a role of kisspeptins Pubertad precoz isosexual definicion the timing of puberty, one study using functional genomics to Pubertad precoz isosexual definicion precoz isosexual definicion ablate Kiss1 neurons suggested that kisspeptin signaling seems to be dispensable for the attainment of female fertility Thus, these findings would not refute the essential role of hypothalamic kisspeptins in the timing of puberty, but rather suggest that redundancy in signaling may help to safeguard
Pubertad precoz isosexual definicion in relatively Pubertad precoz isosexual definicion conditions, at least Pubertad precoz isosexual definicion rodents.
Putative regulators of
Pubertad precoz isosexual definicion One is located in
Pubertad precoz isosexual definicion rostral hypothalamus, mainly at the antero-ventral periventricular nucleus AVPVwhile the other is placed in the arcuate nucleus ARC or its equivalent infundibular region in humans 28, The latter, which is primarily involved in the tonic control of pulsatile 9.
Admittedly, the level of co-expression of these neuropeptides varies depending on the species, the sex and the state of the HPG axis 32, In any event, compelling evidence suggest that NKB may operate as a major stimulatory signal for the auto-regulation of kisspeptin release by KNDy neurons, and hence an important component of the machinery responsible for pulsatile GnRH secretion.
In turn, Dyn would conduct an opposite role, by inhibiting kisspeptin output from KNDy neurons, and thereby suppressing GnRH neurosecretion. Suggestive, as yet incomplete evidence suggests a role of NKB in the control of puberty onset. Thus, it has been shown that central injection of the NKB agonist, senktide, in prepubertal female rats stimulates LH secretion 34while the
Pubertad precoz isosexual definicion expression of NKB gene increases before the rise of Kiss1 mrna in female rodents In the same line, central blockade Pubertad precoz isosexual definicion NKB signaling caused a moderate delay of puberty onset in female rats Recent evidence has shown that the stimulation of NKB signaling or the inhibition of Dyn induces early puberty onset in female rats These
Pubertad precoz isosexual definicion are compatible with the view that the inhibitory effect of Dyn on kisspeptin neurosecretion decreases at the time of puberty, while the stimulatory effect of NKB gradually augments during this period.
Another group of putative modulators of kisspeptin signaling are the metabolic factors, which are known to be potent modifiers of puberty onset. Among them, a major player is the adipose hormone, leptin The unequivocal essential role of leptin in the control of puberty attested by the alterations in pubertal timing observed in conditions of leptin deficiency or morbid
Pubertad precoz isosexual definicion excess, which are often associated with delayed or advanced puberty, respectively 39, In this context, experimental evidence has suggested that leptin is a positive modulator of Kiss1 Pubertad precoz isosexual definicion precoz isosexual definicion a phenomenon that can contribute to transmitting the metabolic modulation puberty onset.
In addition, expression of the gene encoding the leptin receptor has been documented in a fraction of ARC kisspeptin neurons in mice and ewes 42, Nonetheless, whether leptin modulated Kiss1 neurons directly or indirectly has been the subject of intense debate, and studies involving selective elimination of leptin receptors from Kiss1 neurons congenitally, using the Cre-loxP technology, suggest that leptin signaling in this neuronal population dispensable for attainment of reproductive competence 48while other studied have failed to detect a significant amount of functional leptin receptors in Kiss1 neurons before puberty 49, These findings, together with the observations that leptin does influence Kiss1 neurons, would suggest a predominantly indirect mode of action, in which intermediary pathways and signals would play a
Pubertad precoz isosexual Pubertad precoz isosexual definicion role.
Among these, neuronal pathways originating from the ventral pre-mammillary nucleus PMV 51and others using nitric oxide as major transmitter And Future Directions Puberty, as fascinating developmental phenomenon, has drawn considerable attention, and numerous clinical and Pubertad precoz isosexual definicion studies, conducted in different mammalian species during the last decades, have contributed to substantially expand our understanding of the physiology of puberty and the basis of some of its major alterations.
In this context, the
Pubertad precoz isosexual definicion of kisspeptins, as essential regulatory elements for the central control of puberty in mammals, including humans, has revolutionized our knowledge about the intimate mechanisms Pubertad precoz isosexual definicion puberty, allowing to surface novel regulatory pathways whereby different factors, from environmental cues to endogenous hormones, contribute to the precise timing of puberty. While the progress has
Pubertad precoz isosexual definicion astonishing, important aspects of and pubertal physiology remain ill defined and will likely focus considerable attention in the coming years.
Disclosure No potential conflict of interest in relation to this presentation. Endocr Rev 24, Day, F. Sci Rep 5, Lakshman, R. Pediatricse Aksglaede, L.
Parthenon Publishing, New York. Int J Androl 29, ; discussion Pinilla, L. Physiol Rev 92, Oakley, A. Endocr Rev 30, Seminara, S. EndocrinologyNavarro, V. J PhysiolPlant, T. EndocrinologyShahab, M. Mol Cell EndocrinolHan, S.
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A microrna switch regulates the rise in hypothalamic GnRH production before puberty. Hospital Infantil Universitario Miguel Servet. Various malformations affecting the development of the prosencephalon may cause GnRH deficiency combined with deficiency of any or all other pituitary hormones. Menopause and the human hypothalamus: While detailed recapitulation of the results of these studies clearly exceeds the scope of this review, it is important to stress that such analyses have unambiguously documented a sophisticated developmental program of Kiss1 neurons, responsible for their activation during the pubertal maturation 11,
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