Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kisspeptins have recently emerged as essential regulators of gonadotropin secretion and puberty onset. These functions are primarily conducted by stimulation of hypothalamic gonadotropin-releasing hormone (GnRH) secretion. However, relevant aspects of KiSS-1 physiology, including the ontogeny and major signaling systems of its stimulatory action, remain to be fully elucidated. To cover these issues, the effects of kisspeptin-10 on GnRH and LH secretion were monitored at early stages of postnatal maturation, and potential changes in the sensitivity to kisspeptin were assessed along the pubertal transition in the rat. In addition, the signaling cascades involved in kisspeptin-induced GnRH secretion were explored by means of pharmacological blockade using rat hypothalamic explants. Despite sexual immaturity, kisspeptin-10 potently elicited GnRH release ex vivo and LH secretion in vivo at early stages (neonatal to juvenile) of postnatal development. Yet, LH responsiveness to low doses of kisspeptin was enhanced in peri-pubertal animals. Concerning GnRH secretion, the stimulatory action of kisspeptin-10 required activation of phospholipase-C, mobilization of intracellular Ca2+ and recruitment of ERK1/2 and p38 kinases, but was preserved after blockade of type 2 cyclo-oxygenase and prostaglandin synthesis. In summary, our present data document the ontogeny, sensitivity and intracellular signals for the stimulatory action of kisspeptin on the GnRH/LH axis in the rat. Although LH responses to low doses of kisspeptin appeared to be enhanced at puberty, kisspeptin was able to readily activate the GnRH system at early stages of postnatal maturation. These observations further stress the essential role of kisspeptin in normal, and eventually pathological, timing of puberty.
 ...
PMID:Ontogeny and mechanisms of action for the stimulatory effect of kisspeptin on gonadotropin-releasing hormone system of the rat. 1693 Aug 19

Puberty is the end-point of a complex series of developmental events, defined by the dynamic interaction between genetic factors and environmental cues, ultimately leading to the attainment of reproductive capacity. The neuroendocrine basis of puberty has been the subject of extensive investigation in the last decades, and identification of the trigger(s) of puberty onset has drawn considerable attention. In this context, recognition of the fundamental role of kisspeptin (encoded by the KiSS-1 gene) and its receptor GPR54 as major gatekeepers of gonadotropic function in general, and puberty onset in particular, has been a major breakthrough in contemporary Neuroendocrinology. Indeed, during the last 3 years, the so-called KiSS-1/GPR54 system has been substantiated as pivotal regulator of puberty in mammals; the lack of GPR54 signaling being coupled to sexual immaturity (impuberism) in mice and humans. In this review, we will summarize the most salient experimental data (mostly obtained in laboratory animals) demonstrating the key roles of hypothalamic KiSS-1 neurons in the activation of the reproductive axis at puberty, and its regulation by metabolic and, eventually, environmental factors. Whether the KiSS-1 system is the trigger for puberty onset and/or it operates as integrator and effector of up-stream regulatory factors warrants further investigation.
 ...
PMID:Neuroendocrine factors in the initiation of puberty: the emergent role of kisspeptin. 1734 Jan 72