Kisspeptins in Reproductive Biology: Consensus Knowledge and Recent Developments (original) (raw)
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The role of kisspeptin neuropeptide in controlling reproduction
INDIAN JOURNAL OF ANIMAL HEALTH
The pulsatile release of gonadotrophin-releasing hormone (GnRH) from the hypothalamus serves as the ultimate output signal for the regulation of reproductive processes, which integrate a number of elements from both the internal and external environment. A potent endogenous secretagogue of GnRH, kisspeptin, is produced by hypothalamic neurons. Kisspeptin has physiological relevance and a variety of reproductive functions. It controls both the pulsatile GnRH secretion that drives folliculogenesis, spermatogenesis, and steroidogenesis as well as the GnRH surge that causes ovulation in females. It plays a crucial role in the central regulation of the timing of puberty onset and reproduction in animals. Kisspeptin and related substances could therefore be valuable for the development of novel strategies for the management of fertility in farm animals and are now universally recognized as a key player in the control of critical aspects of reproductive development and function from sexual differentiation to regulation of GnRH /gonadotropin secretion.
Kisspeptin: Key Regulator of Hypothalamic-Pituitary-Gonadal Axis
Journal of Babol University of Medical Sciences, 2018
BACKGROUND AND OBJECTIVE: Gonadotropin-Releasing Hormone (GnRH) neurons of hypothalamus are final output of brain for regulation of puberty onset and hypothalamic pituitary gonadal (HPG) axis functions in mammals. However, the mechanisms responsible for release of GnRH neurons are unknown. A number of various factors including neurotransmitters, neuropeptides or different signals have been identified to be involved in the regulation of the secretion of GnRH neurons. Neuronal set of kisspeptin have been recognized recently as critical upstream regulators of GnRH neurons. Given the importance of this issue, in this study a review of various studies and sources about biosynthesis, neuroanatomy, signaling, function and dysfunction of kisspeptin was performed. METHODS: In this review study, new evidence in relation to role of kisspeptin neuropeptide in the reproductive system were investigated by using various databases including pubmed, sciencedirect, nature, springer, wiley, scopus and key words such as kisspeptin, gonads, hypothalamus, GnRH and reproduction were used. FINDINGS: From 145 gained articles, 63 articles were reviewed. Kisspeptin neuropeptide signaling in hypothalamus is required for initiation of puberty and mammalian reproductive function. Kisspeptin neurons stimulate GnRH release and act as central integrator of external and internal signals. Neurones kisspeptin are sensitive to sex steroids, metabolic cues estrogen like compounds. CONCLUSION: Kisspeptin neurons play a vital role in the maturation and function of the HPG axis, including the sexual differentiation of the brain, the timing of puberty, the regulation of gonadotropin secretion and the control of fertility by hormonal and environmental cues.
Journal of chemical neuroanatomy, 2018
Reproductive function is regulated by the hypothalamic-pituitary-gonads (HPG) axis. Hypothalamic neurons synthesizing kisspeptin play a fundamental role in the central regulation of the timing of puberty onset and reproduction in mammals. Kisspeptin is a regulator of gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH). In female rodent, the kisspeptin (encoded by kiss1 gene), neurokinin B (Tac3) and dynorphin neurons form the basis for the "KNDy neurons" in the arcuate nucleus and play a fundamental role in the regulation of GnRH/LH release. Furthermore, various factors including neurotransmitters and neuropeptides may cooperate with kisspeptin signaling to modulate GnRH function. Many neuropeptides including proopiomelanocortin, neuropeptide Y, agouti-related protein, and other neuropeptides, as well as neurotransmitters, dopamine, norepinephrine and γ-aminobutyric acid are suggested to control feeding and HPG axis, the underlying mechanisms are not well kn...
Fertility & Reproduction
Kisspeptin is a class of neuropeptides that are the product of the Kiss1 gene. These neuropeptides play an important role in maintaining gonadotropin-releasing hormone (GnRH) levels and their release through hypothalamic neurons. Subsequently, they also play an important role in maintaining gonadotropin levels, as GnRH levels stimulate the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which allow induction of gametogenesis of pubertal maturation. The importance of the Kiss1 gene in reproduction became evident when natural mutations in this gene were discovered, which were associated with hypothalamic hypogonadism (HH) and delayed puberty. Kisspeptin and its KISS1R receptors are expressed in the mammalian ovary. The putative role of the Kisspeptin system in the ovary directly controls oocyte maturation, follicular development, and ovulation in an autocrine and paracrine fashion. These essential facts of kisspeptin and its receptor are necessary to mainta...
Endocrinology, 2006
Kisspeptins, products of the KiSS-1 gene with ability to bind G protein-coupled receptor 54 (GPR54), have been recently identified as major gatekeepers of reproductive function with ability to potently activate the GnRH/LH axis. Yet, despite the diversity of functional states of the female gonadotropic axis, pharmacological characterization of this effect has been mostly conducted in pubertal animals or adult male rodents, whereas similar studies have not been thoroughly conducted in the adult female. In this work, we evaluated maximal LH and FSH secretory responses to kisspeptin-10, as well as changes in sensitivity and hypothalamic expression of KiSS-1 and GPR54 genes, in different physiological and experimental models in the adult female rat. Kisspeptin-10 (1 nmol, intracerebroventricular) was able to elicit robust LH bursts at all phases of the estrous cycle, with maximal responses at estrus; yet, in diestrus LH, responses to kisspeptin were detected at doses as low as 0.1 pmol. In contrast, high doses of kisspeptin only stimulated FSH secretion at diestrus. Removal of ovarian sex steroids did not blunt the ability of kisspeptin to further elicit stimulated LH and FSH secretion, but restoration of maximal responses required replacement with estradiol and progesterone. Finally, despite suppressed basal levels, LH and FSH secretory responses to kisspeptin were preserved in pregnant and lactating females, although the magnitude of LH bursts and the sensitivity to kisspeptin were much higher in pregnant dams. Interestingly, hypothalamic KiSS-1 gene expression significantly increased during pregnancy, whereas GPR54 mRNA levels remained unaltered. In summary, our current data document for the first time the changes in hypothalamic expression of KiSS-1 system and the gonadotropic effects (maximal responses and sensitivity) of kisspeptin in different functional states of the female reproductive axis. The present data may pose interesting implications in light of the potential therapeutic use of kisspeptin analogs in the pharmacological manipulation of the gonadotropic axis in the female.
Kisspeptin: A Central Regulator of Reproduction in Mammals
SVU-International Journal of Veterinary Sciences, 2020
The discovery of the role of kisspeptin neurons in the regulation of mammalian reproduction in 2003 was one of the biggest breakthroughs in reproductive endocrinology within the last few decades. Research during the past two decades since the discovery of kisspeptin has been unveiling the mechanism of how the hypothalamic kisspeptin neurons control reproductive functions through regulation of gonadotropin-releasing hormone (GnRH) secretion. This article aims to overview kisspeptin research, including the most recent studies from ours and other research groups, and to discuss the possibility of new strategies to control reproductive functions in mammals. In the first section, we introduce the critical role of kisspeptin neurons in puberty onset and reproductive functions in mammals, including the regulation of two modes of GnRH/gonadotropin secretion, namely pulsatile and surge modes. The next section focuses more on the mechanism of how the kisspeptin neurons in the arcuate nucleus in the hypothalamus precisely controls GnRH pulse using other two neuropeptides, neurokinin B and dynorphin A. The article also discusses the mechanism suppressing reproductive function during lactation and other stress conditions through inhibition of kisspeptin neurons and consequent GnRH/gonadotropin secretion, to provide insights on the possibility of new strategies to improve reproductive performance in mammals including domestic farm animals.
Role of Kisspeptin on Hypothalamic-Pituitary-Gonadal Pathology and Its Effect on Reproduction
Cureus
Kisspeptin is a neuropeptide that plays a significant role in human reproduction by its action on the hypothalamic-pituitary-gonadal (HPG) axis and functions through a G-protein-coupled receptor called Gprotein-coupled receptor 54/kisspeptin 1 receptor (GPR54/KISS1R). It is encoded by the kisspeptin 1 (KISS1) gene that is mainly expressed in the hypothalamus. Kisspeptins are also recognized as vital aspects of maturation and proper function of the reproductive system in both males and females. It also plays its role in the onset of puberty, sexual patterns, desires, ovum development in women, sperm quality in men, feedback mechanisms, pregnancy, and lactation. Studies proved the pathological role of kisspeptin dysregulation in disorders like polycystic ovarian syndrome (PCOS) and infertility. Mutations in the KISS1 gene also contribute to precocious puberty or hypogonadotropic hypogonadism, depending upon the nature of mutations. Levels of kisspeptin also aid in the identification of a few pregnancy-related complications like preeclampsia, intrauterine growth restriction, and act as a marker of miscarriage. Due to the wide range of effects that kisspeptin has on the reproductive axis, investigations are being carried out to develop it as a diagnostic marker, treat diseases like hypogonadism and PCOS, and solve infertility issues.
Kisspeptins in human reproduction-future therapeutic potential
Kisspeptins in human reproduction—future therapeutic potential, 2012
Objective Kisspeptins (Kps), were first found to regulate the hypothalamopituitary-gonadal axis (HPG) axis in 2003, when two groups-demonstrated that mutations of GPR54 causes idiopathic hypogonadotropic hypogonadism (IHH) characterized by delayed puberty. Objective of this review is to highlight both animal and human discoveries in KISS1/ GPR54 system in last decade and extrapolate the therapeutic potential in humans from till date human studies. Design A systematic review of international scientific literature by a search of PUBMED and the authors files was done for Kp in reproduction, metabolic control & signal transduction. Setting None Patient(s): In human studies—normal subjects patients with HH, or HA. Main outcome measures: Effects of Kp on puberty, brain sexual maturation, regulation of GnRH secretion, metabolic control of GnRH Neurons (N). Results Kps/GPR54 are critical for brain sexual maturation, puberty and regulation of reproduction. Kps have been implicated in mediating signals to GnRH N—positive and negative feedback, metabolic input. Ability of Kp neurons to coordinate signals impinging on the HPG axis makes it one of most important regulators of reproductive axis since GnRH N’s lack many receptors, with Kp neurons serving as upstream modulators. Conclusions Kps have proven as pivotal regulators of the reproduction, with the ability to integrate signals from both internal and external sources. Knowledge about signaling mechanisms involved in Kp stimulation of GnRH and with human studies has made it possible that therapeutically available Kp agonists/antagonists may be used for treatment of delayed puberty/HH, Hypothalamic amenorrhea and in prevention of spread of malignant ovarian/gonadal malignancies along with uses in some eating disorders. Keywords Kisspeptins . KISS1 receptor . Idiopathic hypogonadotropic hypogonadism . Puberty initiation . Sexual maturation control . Negative feedback control . Positive feedback control . Metabolic control of reproduction
The role of kisspeptin signalling in control of reproduction in genetically similar species
Sudanese journal of paediatrics, 2016
Kisspeptin (previously known as metastin) is a protein encoded by the KISS-1 gene in humans. Kisspeptin producing neurons seem to bridge the gap between the sex steroid levels and feedback mechanisms that control the gonadotropin releasing hormone secretion. Since 2003, there are many studies on the facets of neuroendocrine networks that control puberty and fertility. These have explored the role of Kisspeptins in puberty and fertility using animal models. Kisspeptins are universally recognized as essential activators of the gonadotropic axis and they play an essential role in the metabolic regulation of fertility. Moreover, novel aspects of Kisspeptins/G-protein coupled receptor 54 or Kisspeptin receptor (KPs/GPR54) physiology have demonstrated the Kisspeptins involvement in the neuroendocrine control of ovulation. In this article, the authors highlight the outcome of the most recent work on Kisspeptin role in reproduction in human and animal models and give an opinion on future pe...
Molecular and Cellular Endocrinology, 2006
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 Ca 2+ 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.