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Marilena Marraudino, Mariangela Martini, Sara Trova, Alice Farinetti, Giovanna Ponti, Stefano Gotti, GianCarlo Panzica
The kisspeptin system is clustered in two main groups of cell bodies (the periventricular region, RP3V and the arcuate nucleus, ARC) that send fibers mainly to the GnRH neurons and in a few other locations, including the paraventricular nucleus, PVN. In physiological conditions, gonadal hormones modulate the kisspeptin system with expression changes according to different phases of the estrous cycle: the highest being in estrus phase in RP3V and PVN (positive feedback), and in ARC during the diestrus phase (negative feedback)...
March 16, 2018: Brain Research
Ioannis D Kostakis, George Agrogiannis, Aristeidis G Vaiopoulos, Eleni Mylona, Efstratios Patsouris, Gregory Kouraklis, Michael Koutsilieris
PURPOSE: Kisspeptins, which are derived from the gene KISS1, supress tumor progression. We intended to investigate the production of KISS1 and its receptor (KISSR) in gastric cancer. METHODS: The expression of KISS1 and KISS1R in both normal and cancer tissue was examined with immunohistochemistry in tissue specimens of 40 cases of gastric adenocarcinoma. RESULTS: KISS1 expression in normal gastric mucosa was much higher than in malignant mucosa...
January 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Jeremy T Smith, Antonia Roseweir, Michael Millar, Iain Clarke, Robert P Millar
Kisspeptin signalling is indispensable for fertility, stimulating gonadotropin- releasing hormone (GnRH) secretion and mediating gonadal steroid feedback on GnRH neurons. Moreover, kisspeptin neurons have been implicated in other non-reproductive neuroendocrine roles. Kisspeptin appears to also regulate growth hormone secretion but much of the data appear contradictory. We sought to clarify a potential role of kisspeptin in GH regulation by examining the effect of kisspeptin antagonists on growth hormone (GH) secretion in ewes under various physiological conditions...
March 16, 2018: Journal of Endocrinology
Peyton W Weems, Michael N Lehman, Lique M Coolen, Robert L Goodman
Work over the last 15 years on the control of pulsatile LH secretion has focused largely on a set of neurons in the arcuate nucleus (ARC) that contains two stimulatory neuropeptides, critical for fertility in humans (kisspeptin and neurokinin B (NKB)) and the inhibitory endogenous opioid peptide (EOP), dynorphin, and are now known as KNDy (kisspeptin-NKB-dynorphin) neurons. In this review, we consider the role of each of the KNDy peptides in the generation of GnRH pulses and the negative feedback actions of ovarian steroids, with an emphasis on NKB and dynorphin...
2018: Vitamins and Hormones
Ali Abbara, Shakunthala Narayanaswamy, Chioma Izzi-Engbeaya, Alexander N Comninos, Sophie Clarke, Zainab Malik, Deborah Papadopoulou, Ailish Clobentz, Zubair Sarang, Paul Bassett, Channa Jayasena, Waljit S Dhillo
<br>Background: Male testosterone levels decline by 1% per year from the age of 40yrs. Whilst a primary testicular deficit occurs, hypothalamic or pituitary dysregulation may also coexist. This study aimed to compare the hypothalamic response to kisspeptin and the pituitary response to GnRH of older men with those of young men. METHODS: Following 1 hour of baseline sampling, healthy older men (n=5, mean age 59.3±2.9yrs) received a 3 hour intravenous infusion (IVI) of either: vehicle, kisspeptin-54 0...
March 15, 2018: Neuroendocrinology
Laurence Dufourny, Oona Delmas, Ana-Paula Teixeira-Gomes, Caroline Decourt, Joanna H Sliwowska
Somatostatin (SST) a neuropeptide involved in the central modulation of several physiological functions, is co-distributed in the same hypothalamic areas as kisspeptin (KP), the most potent secretagogue of the gonadotropin-releasing hormone (GnRH) secretion known to date. As SST infused intracerebroventricularly (icv) evoked a potent inhibition of GnRH release, we explored neuroanatomical relationships between KP and SST populations in male and female rats. For that, intact males and ovariectomised oestradiol-replaced females were killed and their brains processed in order to simultaneously detect KP, SST and synapsin, a marker for synapses...
March 15, 2018: Journal of Neuroendocrinology
A Acevedo-Rodriguez, A S Kauffman, B D Cherrington, C S Borges, T A Roepke, M Laconi
Reproduction and fertility are regulated via hormones of the hypothalamic-pituitary-gonadal (HPG) axis. Control of this reproductive axis occurs at all levels, including the brain and pituitary, and allows for promotion or inhibition of gonadal sex steroid secretion and function. In addition to guiding proper gonadal development and function, gonadal sex steroids also act in negative and positive feedback loops to regulate reproductive circuitry in the brain, including kisspeptin neurons, thereby modulating overall HPG axis status...
March 9, 2018: Journal of Neuroendocrinology
Tabata Mariz Bohlen, Marina Augusto Silveira, Daniella do Carmo Buonfiglio, Hildebrando Candido Ferreira-Neto, José Cipolla-Neto, Jose Donato, Renata Frazao
The reproduction of seasonal breeders is modulated by exposure to light in an interval of 24 h defined as photoperiod. The interruption of reproductive functions in seasonally breeding rodents is accompanied by the suppression of the Kiss1 gene expression, which is known to be essential for reproduction. In non-seasonal male rodents, such as rats and mice, short-day photoperiod (SP) conditions or exogenous melatonin treatment also have anti-gonadotropic effects; however, whether photoperiod is able to modulate the puberty onset or Kiss1 gene expression in mice is unknown...
2018: Frontiers in Endocrinology
Ariclecio Cunha de Oliveira, Sandra Andreotti, Rogério António Laurato Sertie, Amanda Baron Campana, André Ricardo Gomes de Proença, Renata Prado Vasconcelos, Keciany Alves de Oliveira, Andrelina Noronha Coelho-de-Souza, José Donato Junior, Fábio Bessa Lima
AIMS: Melatonin treatment has been reported to be capable of ameliorating metabolic diabetes-related abnormalities but also to cause hypogonadism in rats. We investigated whether the combined treatment with melatonin and insulin can improve insulin resistance and other metabolic disorders in rats with streptozotocin-induced diabetes during neonatal period and the repercussion of this treatment on the hypothalamic-pituitary-gonadal axis. MAIN METHODS: At the fourth week of age, diabetic animals started an 8-wk treatment with only melatonin (0...
February 28, 2018: Life Sciences
Artur Pałasz, Marcelina Pałka, Łukasz Filipczyk, Itiana Castro Menezes, Ewa Rojczyk, John J Worthington, Aneta Piwowarczyk-Nowak, Marek Krzystanek, Ryszard Wiaderkiewicz
Neuroleptics modulate the expression level of some regulatory neuropeptides in the brain. However, if these therapeutics influence the peptidergic circuits in the amygdala remains unclear. This study specifies the impact profile of the classical antipsychotic drugs on mRNA expression of the spexin/NPQ, kisspeptin-1 and POMC in the rat amygdala. Animals were treated with haloperidol and chlorpromazine for 28 days prior to transcript quantification via qPCR. Haloperidol and chlorpromazine induced a change in the expression of all neuropeptides analyzed...
February 27, 2018: Journal of Neural Transmission
Toshiya Matsuzaki, Altankhuu Tungalagsuvd, Munkhsaikhan Munkhzaya, Takeshi Iwasa, Kiyohito Yano, Yiliyasi Mayila, Takako Tokui, Rie Yanagihara, Sumika Matsui, Takeshi Kato, Akira Kuwahara, Minoru Irahara
Kisspeptin/neurokinin B (NKB)/dynorphin (Dyn) (KNDy) neuron in hypothalamic arcuate nucleus plays a key role in GnRH/LH pulsatile secretion. We aimed to determine whether stimulation of NKB/neurokinin 3 receptor (NK3R) signaling and inhibition of Dyn/kappa-opioid receptor (KOR) signaling recover LH secretion that is suppressed by acute fasting in male rats. Furthermore, we determined dose dependent effect of NKB/NK3R signaling on serum LH level under acute fasting condition in male mice. Mature male rats were injected saline (0...
February 23, 2018: Endocrine Journal
Muhammad Shahab, Margaret Lippincott, Yee-Ming Chan, Addie Davies, Paulina M Merino, Lacey Plummer, Veronica Mericq, Stephanie Seminara
Context: Hypothalamic kisspeptin signaling plays a critical role in the initiation and maintenance of reproductive function. Biallelic mutations in the coding sequence of KISS1R (GPR54) have been identified in patients with idiopathic hypogonadotropic hypogonadism (IHH), but it is unknown whether biallelic variants can also be associated with related reproductive disorders. Case description: A missense homozygous variant (c.890G>T p.R297L) in KISS1R was identified in a child who presented with microphallus and bilateral cryptorchidism...
February 14, 2018: Journal of Clinical Endocrinology and Metabolism
A Abbara, R Islam, S A Clarke, L Jeffers, G Christopoulos, A N Comninos, R Salim, S A Lavery, N L Vuong, P Humaidan, T W Kelsey, G H Trew, W S Dhillo
OBJECTIVE: Ovarian hyperstimulation syndrome (OHSS) is a serious iatrogenic condition, predominantly related to the hormone used to induce oocyte maturation during IVF treatment. Kisspeptin is a hypothalamic neuropeptide that has recently been demonstrated to safely trigger final oocyte maturation during IVF treatment even in women at high risk of OHSS. However to date, the safety of kisspeptin has not been compared to current hormonal triggers of oocyte maturation. DESIGN: We conducted a retrospective single-centre cohort study investigating symptoms and clinical parameters of early OHSS in women at high risk of OHSS (antral follicle count or total number of follicles on day of trigger ≥23) triggered with hCG (n=40), GnRH agonist (GnRHa; n=99), or kisspeptin (n=122) at Hammersmith Hospital IVF unit, London, UK (2013-2016)...
February 15, 2018: Clinical Endocrinology
Daphné Capela, Carlos Dombret, Kevin Poissenot, Manon Poignant, Aude Malbert-Colas, Isabelle Franceschini, Matthieu Keller, Sakina Mhaouty-Kodja
The neural circuitry processing male sexual behavior is tightly regulated by testosterone and its neural metabolite estradiol. The present study evaluated the effects of adult exposure to low doses of nonylphenol (NP), a widespread environmental contaminant, on the neuroendocrine regulation of testosterone and expression of sexual behavior. Oral exposure of C57BL/6J males to NP (0.5, 5 or 50 μg/kg/day) for 4 weeks did not affect circulating levels of testosterone or the kisspeptin system, a key regulator of the gonadotropic axis...
February 14, 2018: Scientific Reports
Sarah Delmas, Robert Porteous, Dave H Bergin, Allan E Herbison
The roles of kisspeptin signaling outside the hypothalamus in the brain are unknown. We examined here the impact of Kiss1r-deletion on hippocampus-related behaviors of anxiety and spatial learning in adult male mice using two mouse models. In the first, global Kiss1r-null and control mice were gonadectomized (GDX KISS1R-KO). In the second, KISS1R signalling was rescued selectively in gonadotropin-releasing hormone neurons to generate Kiss1r-null mice with normal testosterone levels (intact KISS1R-KO). Intact KISS1R-KO rescue mice were found to spend twice as much time in the open arms of the elevated plus maze (EPM) compared to controls (P < 0...
February 12, 2018: Scientific Reports
Xin-Yuan Cao, Xu Hua, Jian-Wei Xiong, Wen-Ting Zhu, Jun Zhang, Ling Chen
Triclosan (TCS), a broad-spectrum antimicrobial agent, is widely used in clinical settings and various personal care products. The aim of this study was to evaluate the influence of TCS on reproductive endocrine and function. Here, we show that the exposure of adult female mice to 10 or 100 mg/kg/day TCS caused prolongation of diestrus, and decreases in antral follicles and corpora lutea within 2 weeks. TCS mice showed decreases in the levels of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and progesterone, and gonadotrophin-releasing hormone (GnRH) mRNA with the lack of LH surge and elevation of prolactin (PRL)...
2018: Frontiers in Molecular Neuroscience
Aleisha M Moore, Kathryn A Lucas, Robert L Goodman, Lique M Coolen, Michael N Lehman
Kisspeptin/Neurokinin B/Dynorphin (KNDy) neurons of the arcuate nucleus (ARC) play a key role in the regulation of fertility. The ability to detect features of KNDy neurons that are essential for fertility may require three-dimensional (3D) imaging of the complete population. Recently developed protocols for optical tissue clearing permits 3D imaging of neuronal populations in un-sectioned brains. However, these techniques have largely been described in the mouse brain. We report 3D imaging of the KNDy cell population in the whole rat brain and sheep hypothalamus using immunolabelling and modification of a solvent-based clearing protocol, iDISCO...
February 2, 2018: Scientific Reports
Hyo-Eun Son, Kyeong-Min Kim, Eun-Jung Kim, Won-Gu Jang
Kisspeptin-10 (KP-10) acts as a tumor metastasis suppressor via its receptor, G-protein-coupled receptor 54 (GPR54). The KP-10-GPR54 system plays an important role in embryonic kidney development. However, its function in osteoblast differentiation is unknown. Osteoblast differentiation is controlled by a range of hormones and cytokines, such as bone morphogenetic protein (BMPs), and multiple transcription factors, such as Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), and Distal-less homeobox 5 (Dlx5)...
February 1, 2018: Scientific Reports
Tao Feng, Jiahua Bai, Xiaoling Xu, Yan Liu
Kisspeptin and its receptor, GPR54, are regarded as key regulators of and catalysts for male puberty onset, and also fundamental gatekeepers of spermatogenesis in mammals. Consequently, the loss function of kisspeptin or GPR54 leads to a symptom of hypogonadotropic hypogonadism (HH) in human and HH accompanied by lower gonadotrophic hormone levels, smaller testes, impaired spermatogenesis and abnormal sexual maturation in mice. Besides its well- recognized functions in hypothalamus before and during puberty, accumulating data strongly support kisspeptin production in tests, and participation in somatic and germ cell development and sperm functions as well...
January 28, 2018: Current Drug Metabolism
Szabolcs Takács, Zsuzsanna Bardóczi, Katalin Skrapits, Balázs Göcz, Viktória Váczi, Zsófia Maglóczky, Iván Szűcs, Gergely Rácz, András Matolcsy, Waljit S Dhillo, Masahiko Watanabe, Andrea Kádár, Csaba Fekete, Imre Kalló, Erik Hrabovszky
Kisspeptin (KP) synthesizing neurons of the hypothalamic infundibular region are critically involved in the central regulation of fertility; these cells regulate pulsatile gonadotropin-releasing hormone (GnRH) secretion and mediate sex steroid feedback signals to GnRH neurons. Fine structural analysis of the human KP system is complicated by the use of post mortem tissues. To gain better insight into the neuroanatomy of the somato-dendritic cellular compartment, we introduced the diolistic labeling of immunohistochemically identified KP neurons using a gene gun loaded with the lipophilic dye, DiI...
January 29, 2018: Brain Structure & Function
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