-
Current Opinion in Pharmacology Dec 2022Kisspeptin is a hypothalamic neuropeptide that acts via the hypothalamus to stimulate hypothalamic gonadotrophin-releasing hormone secretion and downstream gonadotrophin... (Review)
Review
Kisspeptin is a hypothalamic neuropeptide that acts via the hypothalamus to stimulate hypothalamic gonadotrophin-releasing hormone secretion and downstream gonadotrophin release. In health, kisspeptin induces normal puberty and modulates ovulation in healthy women. Hypothalamic kisspeptin expression is reduced in several functional reproductive disorders; thus, treating such conditions with kisspeptin is conceptually attractive. Recent studies have demonstrated that kisspeptin can induce a more physiological degree of oocyte maturation during in vitro fertilisation treatment that can reduce the risk of potentially life-threatening complications such as ovarian hyperstimulation syndrome seen with human chorionic gonadotrophin. Furthermore, chronic use of kisspeptin could potentially restore reproductive health in females with hypothalamic amenorrhoea, treat hyposexual drive disorder in otherwise healthy males and has potential indications in polycystic ovary syndrome, osteoporosis and metabolic dysfunction-associated fatty liver disease. Finally, kisspeptin analogues could potentially overcome some of the pharmacological challenges associated with the natural forms of kisspeptin such as short duration of action and development of tachyphylaxis.
Topics: Male; Female; Humans; Kisspeptins; Ovarian Hyperstimulation Syndrome; Gonadotropin-Releasing Hormone; Fertilization in Vitro; Hypothalamus
PubMed: 36413854
DOI: 10.1016/j.coph.2022.102319 -
MMW Fortschritte Der Medizin Mar 2023
Topics: Humans; Kisspeptins
PubMed: 36826636
DOI: 10.1007/s15006-023-2449-3 -
European Journal of Obstetrics,... Oct 2012To investigate whether the serum levels of metastin and PIGF and chitotriosidase activity early in pregnancy differ in women who develop pre-eclampsia from those who...
OBJECTIVE
To investigate whether the serum levels of metastin and PIGF and chitotriosidase activity early in pregnancy differ in women who develop pre-eclampsia from those who remain normotensive.
STUDY DESIGN
A retrospective case-control study of prospectively collected data. Thirty healthy pregnant women and 31 women with pre-eclampsia were included in the study. Serum samples were collected at 11-14 weeks and stored at -70°C. Levels of metastin, PIGF and chitotriosidase activity were measured in serum from pregnant women with subsequent development of pre-eclampsia and matched controls.
RESULTS
Mean maternal serum metastin (1554 ± 385 pmol/L vs 1995 ± 375 pmol/L, p<0.001) and PIGF (111.9 ± 7.0 pg/mL vs 124.9 ± 3.5 pg/mL, p<0.001) levels were significantly lower and chitotriosidase activity was significantly higher (681.6 ± 248.3 nmol/mL/h vs 527.7 ± 223.1 nmol/mL/h, p<0.01) in women who subsequently developed pre-eclampsia than in those who remained normotensive. The areas under the curve equal to 0.797, 0.831 and 0.681 (p<0.001, p<0.001 and p<0.01) for metastin, PIGF, and chitotriosidase respectively were determined for the prediction of pre-eclampsia.
CONCLUSIONS
Metastin and PIGF levels and chitotriosidase activity are altered in the first trimester serum of women destined to become pre-eclamptic, reflecting placental dysfunction. Metastin, like PIGF, may have a potential to be used as a first-trimester biomarker of pre-eclampsia.
Topics: Adult; Biomarkers; Case-Control Studies; Down-Regulation; Female; Hexosaminidases; Humans; Kisspeptins; Placenta Growth Factor; Pre-Eclampsia; Pregnancy; Pregnancy Proteins; Pregnancy Trimester, First; Retrospective Studies; Up-Regulation
PubMed: 22770630
DOI: 10.1016/j.ejogrb.2012.06.016 -
Seminars in Reproductive Medicine May 2019Kisspeptin has well-established critical roles in the control of reproduction and fertility. Recently, evidence has emerged that suggests kisspeptin may have additional... (Review)
Review
Kisspeptin has well-established critical roles in the control of reproduction and fertility. Recently, evidence has emerged that suggests kisspeptin may have additional roles in the regulation of glucose homeostasis. Conflicting reports on the effects of kisspeptin on insulin secretion in animal models have been published, which cannot be fully accounted for by the different kisspeptin isoforms and range of kisspeptin doses used in these studies. Human studies have demonstrated associations between circulating kisspeptin levels and measures of insulin secretion and insulin resistance; and the only published interventional study has confirmed kisspeptin enhances glucose-stimulated insulin secretion in humans. Further studies are required to elucidate the mechanisms underlying the effects of kisspeptin on the pancreatic β-cell and to determine the therapeutic potential of kisspeptin receptor agonist in the treatment of disorders of glucose homeostasis.
Topics: Animals; Fertility; Glucose; Glucose Metabolism Disorders; Homeostasis; Humans; Insulin; Insulin Secretion; Kisspeptins; Receptors, Kisspeptin-1; Reproduction
PubMed: 31869842
DOI: 10.1055/s-0039-3400242 -
The Journal of Clinical Endocrinology... Feb 2003Metastin is a novel peptide that was recently isolated from human placenta as the endogenous ligand of an orphan heptahelical receptor, hOT7T175. Metastin has been shown...
Metastin is a novel peptide that was recently isolated from human placenta as the endogenous ligand of an orphan heptahelical receptor, hOT7T175. Metastin has been shown to suppress the motility of hOT7T175-transfected melanoma cells; however, studies of the physiological function of metastin have begun only recently. To investigate the possibility that metastin is an endocrine peptide, we determined the immunoreactive (ir-) metastin concentration in human plasma using our newly developed, sensitive, and specific two-site enzyme immunoassay. The plasma concentrations of ir-metastin in males and females were 1.30 +/- 0.14 (n = 12) and 1.31 +/- 0.37 fmol/ml (n = 10), respectively. As metastin is known to be abundant in human placenta, the ir-metastin concentration in the maternal plasma was then determined. The ir-metastin concentrations were 1230 +/- 346 fmol/ml (n = 11) in the first trimester, 4590 +/- 555 (n = 16) in the second trimester, and 9590 +/- 1640 (n = 12) in the third trimester. On d 5 after delivery, the ir-metastin concentration returned to nearly the nonpregnant level (7.63 +/- 1.33 fmol/ml; n = 10), suggesting that ir-metastin increases in pregnancy and is derived mainly from the placenta. The plasma from both nonpregnant and pregnant women showed a single ir-metastin peak at the same retention time as authentic metastin on reverse phase HPLC analysis, indicating that the major portion of the circulating metastin, as determined by our two-site enzyme immunoassay, represents endogenous metastin. Histochemical studies of human placenta localized metastin mRNA and immunoreactivity to the syncytiotrophoblasts. The present study provides evidence for metastin as a novel placenta-derived hormone in humans.
Topics: Adult; Antibodies, Monoclonal; Female; Humans; Immunoenzyme Techniques; Immunohistochemistry; In Situ Hybridization; Kisspeptins; Male; Placenta; Postpartum Period; Pregnancy; Proteins; RNA, Messenger; Tumor Suppressor Proteins
PubMed: 12574233
DOI: 10.1210/jc.2002-021235 -
Cells Mar 2022Kisspeptin (KP) and kisspeptin receptor (KPR) are essential for the onset of puberty, development of gonads, and maintenance of gonadal function in both males and... (Review)
Review
Kisspeptin (KP) and kisspeptin receptor (KPR) are essential for the onset of puberty, development of gonads, and maintenance of gonadal function in both males and females. Hypothalamic KPs and KPR display a high degree of sexual dimorphism in expression and function. KPs act on KPR in gonadotropin releasing hormone (GnRH) neurons and induce distinct patterns of GnRH secretion in males and females. GnRH acts on the anterior pituitary to secrete gonadotropins, which are required for steroidogenesis and gametogenesis in testes and ovaries. Gonadal steroid hormones in turn regulate the KP neurons. Gonadal hormones inhibit the KP neurons within the arcuate nucleus and generate pulsatile GnRH mediated gonadotropin (GPN) secretion in both sexes. However, the numbers of KP neurons in the anteroventral periventricular nucleus and preoptic area are greater in females, which release a large amount of KPs in response to a high estrogen level and induce the preovulatory GPN surge. In addition to the hypothalamus, KPs and KPR are also expressed in various extrahypothalamic tissues including the liver, pancreas, fat, and gonads. There is a remarkable difference in circulating KP levels between males and females. An increased level of KPs in females can be linked to increased numbers of KP neurons in female hypothalamus and more KP production in the ovaries and adipose tissues. Although the sexually dimorphic features are well characterized for hypothalamic KPs, very little is known about the extrahypothalamic KPs. This review article summarizes current knowledge regarding the sexual dimorphism in hypothalamic as well as extrahypothalamic KP and KPR system in primates and rodents.
Topics: Animals; Arcuate Nucleus of Hypothalamus; Female; Gonadotropin-Releasing Hormone; Kisspeptins; Male; Sex Characteristics; Sexual Maturation
PubMed: 35406710
DOI: 10.3390/cells11071146 -
Journal of Neuroendocrinology May 2022Mathematical modelling is an indispensable tool in modern biosciences, enabling quantitative analysis and integration of biological data, transparent formulation of our... (Review)
Review
Mathematical modelling is an indispensable tool in modern biosciences, enabling quantitative analysis and integration of biological data, transparent formulation of our understanding of complex biological systems, and efficient experimental design based on model predictions. This review article provides an overview of the impact that mathematical models had on GnRH research. Indeed, over the last 20 years mathematical modelling has been used to describe and explore the physiology of the GnRH neuron, the mechanisms underlying GnRH pulsatile secretion, and GnRH signalling to the pituitary. Importantly, these models have contributed to GnRH research via novel hypotheses and predictions regarding the bursting behaviour of the GnRH neuron, the role of kisspeptin neurons in the emergence of pulsatile GnRH dynamics, and the decoding of GnRH signals by biochemical signalling networks. We envisage that with the advent of novel experimental technologies, mathematical modelling will have an even greater role to play in our endeavour to understand the complex spatiotemporal dynamics underlying the reproductive neuroendocrine system.
Topics: Gonadotropin-Releasing Hormone; Kisspeptins; Models, Theoretical; Neurons; Reproduction
PubMed: 35080068
DOI: 10.1111/jne.13085 -
The Lancet. Diabetes & Endocrinology Sep 2013
Review
Topics: Animals; Gonadotropin-Releasing Hormone; Humans; Hypothalamus; Kisspeptins; Time Factors
PubMed: 24622258
DOI: 10.1016/S2213-8587(13)70098-6 -
Seminars in Reproductive Medicine Mar 2019Successful reproduction is dependent not only on hormonal endocrine responses but also on suitable partner selection, copulatory acts, as well as associated emotional,... (Review)
Review
Successful reproduction is dependent not only on hormonal endocrine responses but also on suitable partner selection, copulatory acts, as well as associated emotional, behavioral, and cognitive processes many of which are supported by the limbic system. The reproductive hormone kisspeptin (encoded by the / gene) is now recognized as the key orchestrator of the reproductive axis. In addition to the hypothalamus, prominent kisspeptin neuronal populations have been identified throughout limbic and paralimbic brain regions across an assortment of species. In this review, we detail the emerging roles of kisspeptin signaling in the broader aspects of behavioral, emotional, and cognitive control. Recent studies from zebrafish through humans have provided new molecular and neural insights into the complex role of kisspeptin in interpreting olfactory and auditory cues to govern sexual partner preference, in regulating copulatory behaviors and in influencing mood and emotions. Furthermore, emerging roles for kisspeptin in facilitating memory and learning are also discussed. To this end, these findings shed new light onto the importance of kisspeptin signaling, while informing the pharmacological development of kisspeptin as a potential therapeutic strategy for individuals suffering from associated reproductive, emotional, and cognitive disorders.
Topics: Animals; Cognition; Female; Humans; Kisspeptins; Male; Receptors, Odorant; Reproductive Behavior; Sexual Behavior, Animal; Signal Transduction
PubMed: 31847025
DOI: 10.1055/s-0039-3400239 -
Journal of Neuroendocrinology Jul 2018Puberty involves a series of morphological, physiological and behavioural changes during the last part of the juvenile period that culminates in the attainment of... (Review)
Review
Puberty involves a series of morphological, physiological and behavioural changes during the last part of the juvenile period that culminates in the attainment of fertility. The activation of the pituitary-gonadal axis by increased hypothalamic secretion of gonadotrophin-releasing hormone (GnRH) is an essential step in the process. The current hypothesis postulates that a loss of transsynaptic inhibition and a rise in excitatory inputs are responsible for the activation of GnRH release. Similarly, a shift in the balance in the expression of puberty activating and puberty inhibitory genes exists during the pubertal transition. In addition, recent evidence suggests that the epigenetic machinery controls this genetic balance, giving rise to the tantalising possibility that epigenetics serves as a relay of environmental signals known for many years to modulate pubertal development. Here, we review the contribution of epigenetics as a regulatory mechanism in the hypothalamic control of female puberty.
Topics: Animals; Epigenesis, Genetic; Female; Gonadotropin-Releasing Hormone; Humans; Hypothalamus; Kisspeptins; Neurons; Puberty; Sexual Maturation
PubMed: 29520866
DOI: 10.1111/jne.12589