scholarly journals Arcuate nucleus kisspeptin response to increased nutrition in rams

2019 ◽  
Vol 31 (11) ◽  
pp. 1682 ◽  
Author(s):  
S. E. Rietema ◽  
P. A. R. Hawken ◽  
C. J. Scott ◽  
M. N. Lehman ◽  
G. B. Martin ◽  
...  
Keyword(s):  
Arcuate Nucleus ◽  
Preoptic Area ◽  
Pulse Generator ◽  
Pulse Frequency ◽  
Nutritional Supplementation ◽  
Environmental Cues ◽  
Dorsomedial Hypothalamus ◽  
Gonadotrophin Releasing Hormone ◽  
Kndy Neurons

Rams respond to acute nutritional supplementation by increasing the frequency of gonadotrophin-releasing hormone (GnRH) pulses. Kisspeptin neurons may mediate the effect of environmental cues on GnRH secretion, so we tested whether the ram response to nutrition involves activation of kisspeptin neurons in the arcuate nucleus (ARC), namely kisspeptin, neurokin B, dynorphin (KNDy) neurons. Rams were given extra lupin grain with their normal ration. Blood was sampled before feeding, and continued until animals were killed for collection of brain tissue at 2 or 11h after supplementation. In supplemented rams, LH pulse frequency increased after feeding, whereas control animals showed no change. Within the caudal ARC, there were more kisspeptin neurons in supplemented rams than in controls and a higher proportion of kisspeptin cells coexpressed Fos, regardless of the time the rams were killed. There were more Fos cells in the mid-ARC and mid-dorsomedial hypothalamus of the supplemented compared with control rams. No effect of nutrition was found on kisspeptin expression in the rostral or mid-ARC, or on GnRH expression in the preoptic area. Kisspeptin neurons in the caudal ARC appear to mediate the increase in GnRH and LH production due to acute nutritional supplementation, supporting the hypothesised role of the KNDy neurons as the pulse generator for GnRH.

scholarly journals The neurobiological mechanism underlying hypothalamic GnRH pulse generation: the role of kisspeptin neurons in the arcuate nucleus

F1000Research ◽  
2020 ◽  
Vol 8 ◽  
pp. 982 ◽  
Author(s):  
Tony M. Plant
Keyword(s):  
Arcuate Nucleus ◽  
Pulse Generator ◽  
Hormone Secretion ◽  
Pulse Generation ◽  
Luteinizing Hormone Secretion ◽  
Gnrh Release ◽  
Exciting Time ◽  
Kndy Neurons ◽  
Hypophysial Portal

This review recounts the origins and development of the concept of the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator. It starts in the late 1960s when striking rhythmic episodes of luteinizing hormone secretion, as reflected by circulating concentrations of this gonadotropin, were first observed in monkeys and ends in the present day. It is currently an exciting time witnessing the application, primarily to the mouse, of contemporary neurobiological approaches to delineate the mechanisms whereby Kiss1/NKB/Dyn (KNDy) neurons in the arcuate nucleus of the hypothalamus generate and time the pulsatile output of kisspeptin from their terminals in the median eminence that in turn dictates intermittent GnRH release and entry of this decapeptide into the primary plexus of the hypophysial portal circulation. The review concludes with an examination of questions that remain to be addressed.

scholarly journals The neurobiological mechanism underlying hypothalamic GnRH pulse generation: the role of kisspeptin neurons in the arcuate nucleus

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 982 ◽  
Author(s):  
Tony M. Plant
Keyword(s):  
Arcuate Nucleus ◽  
Pulse Generator ◽  
Hormone Secretion ◽  
Pulse Generation ◽  
Luteinizing Hormone Secretion ◽  
Gnrh Release ◽  
Exciting Time ◽  
Kndy Neurons ◽  
Hypophysial Portal

This review recounts the origins and development of the concept of the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator. It starts in the late 1960s when striking rhythmic episodes of luteinizing hormone secretion, as reflected by circulating concentrations of this gonadotropin, were first observed in monkeys and ends in the present day. It is currently an exciting time witnessing the application, primarily to the mouse, of contemporary neurobiological approaches to delineate the mechanisms whereby Kiss1/NKB/Dyn (KNDy) neurons in the arcuate nucleus of the hypothalamus generate and time the pulsatile output of kisspeptin from their terminals in the median eminence that in turn dictates intermittent GnRH release and entry of this decapeptide into the primary plexus of the hypophysial portal circulation. The review concludes with an examination of questions that remain to be addressed.

scholarly journals Kisspeptin, Neurokinin B, and Dynorphin Act in the Arcuate Nucleus to Control Activity of the GnRH Pulse Generator in Ewes

Endocrinology ◽  
2013 ◽  
Vol 154 (11) ◽  
pp. 4259-4269 ◽  
Author(s):  
Robert L. Goodman ◽  
Stanley M. Hileman ◽  
Casey C Nestor ◽  
Katrina L. Porter ◽  
John M. Connors ◽  
...  
Keyword(s):  
Arcuate Nucleus ◽  
Pulse Generator ◽  
Pulse Frequency ◽  
Afferent Input ◽  
Pulse Generation ◽  
Orphanin Fq ◽  
Neurokinin B ◽  
Control Activity ◽  
Kndy Neurons ◽  
Lh Secretion

Recent work has led to the hypothesis that kisspeptin/neurokinin B/dynorphin (KNDy) neurons in the arcuate nucleus play a key role in GnRH pulse generation, with kisspeptin driving GnRH release and neurokinin B (NKB) and dynorphin acting as start and stop signals, respectively. In this study, we tested this hypothesis by determining the actions, if any, of four neurotransmitters found in KNDy neurons (kisspeptin, NKB, dynorphin, and glutamate) on episodic LH secretion using local administration of agonists and antagonists to receptors for these transmitters in ovariectomized ewes. We also obtained evidence that GnRH-containing afferents contact KNDy neurons, so we tested the role of two components of these afferents: GnRH and orphanin-FQ. Microimplants of a Kiss1r antagonist briefly inhibited LH pulses and microinjections of 2 nmol of this antagonist produced a modest transitory decrease in LH pulse frequency. An antagonist to the NKB receptor also decreased LH pulse frequency, whereas NKB and an antagonist to the receptor for dynorphin both increased pulse frequency. In contrast, antagonists to GnRH receptors, orphanin-FQ receptors, and the N-methyl-D-aspartate glutamate receptor had no effect on episodic LH secretion. We thus conclude that the KNDy neuropeptides act in the arcuate nucleus to control episodic GnRH secretion in the ewe, but afferent input from GnRH neurons to this area does not. These data support the proposed roles for NKB and dynorphin within the KNDy neural network and raise the possibility that kisspeptin contributes to the control of GnRH pulse frequency in addition to its established role as an output signal from KNDy neurons that drives GnRH pulses.

scholarly journals Stress-induced inhibition of LH pulses in female rats: role of GABA in arcuate nucleus

2015 ◽  
Vol 55 (1) ◽  
pp. 9-19 ◽  
Author(s):  
XiaoFeng Li ◽  
Bei Shao ◽  
ChengCheng Lin ◽  
Kevin T O'Byrne ◽  
YuanShao Lin
Keyword(s):  
Arcuate Nucleus ◽  
Pulse Generator ◽  
Reproductive Function ◽  
Pulse Frequency ◽  
Inhibitory Effect ◽  
Female Rats ◽  
Inhibitory Effects ◽  
Corticotrophin Releasing Factor ◽  
Cgp 35348

Stress exerts profound inhibitory effects on reproductive function by suppression of the pulsatile release of GnRH and therefore LH. Besides the corticotrophin-releasing factor (CRF), this effect also might be mediated via GABAergic signaling within the arcuate nucleus (ARC) since its inhibitory effects on LH pulses and increased activity during stress. In the present study, we investigated the role of endogenous GABAergic signaling within the ARC in stress-induced suppression of LH pulses. Ovariectomised oestradiol-replaced rats were implanted with bilateral and unilateral cannulae targeting toward the ARC and lateral cerebral ventricle respectively. Blood samples (25 μl) were taken via chronically implanted cardiac catheters every 5 min for 6 h for measurement of LH pulses. Intra-ARC infusion of GABAAreceptor antagonist, bicuculline (0.2 pmol in 200 nl artificial cerebrospinal fluid (aCSF) each side, three times at 20-min intervals) markedly attenuated the inhibitory effect of lipopolysaccharide (LPS; 25 μg/kg i.v.) but not restraint (1 h) stress on pulsatile LH secretion. In contrast, restraint but not LPS stress-induced suppression of LH pulse frequency was reversed by intra-ARC administration of GABABR antagonist, CGP-35348 (1.5 nmol in 200 nl aCSF each side, three times at 20-min intervals). Moreover, intra-ARC application of either bicuculline or CGP-35348 attenuated the inhibitory effect of CRF (1 nmol in 4 μl aCSF, i.c.v.) on the LH pulses. These data indicate a pivotal and differential role of endogenous GABAAand GABABsignaling mechanisms in the ARC with respect to mediating immunological and psychological stress-induced suppression of the GnRH pulse generator respectively.

scholarly journals Suppression of the GnRH Pulse Generator by Neurokinin B Involves a κ-Opioid Receptor-Dependent Mechanism

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 4894-4904 ◽  
Author(s):  
P. Grachev ◽  
X. F. Li ◽  
J. S. Kinsey-Jones ◽  
A. L. di Domenico ◽  
R. P. Millar ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Pulse Generator ◽  
Pulse Frequency ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Neurokinin B ◽  
Kndy Neurons ◽  
Lh Secretion ◽  
Dose Dependent

Abstract Neurokinin B (NKB) and its receptor (NK3R) are coexpressed with kisspeptin, Dynorphin A (Dyn), and their receptors [G-protein-coupled receptor-54 (GPR54)] and κ-opioid receptor (KOR), respectively] within kisspeptin/NKB/Dyn (KNDy) neurons in the hypothalamic arcuate nucleus (ARC), the proposed site of the GnRH pulse generator. Much previous research has employed intracerebroventricular (icv) administration of KNDy agonists and antagonists to address the functions of KNDy neurons. We performed a series of in vivo neuropharmacological experiments aiming to determine the role of NKB/NK3R signaling in modulating the GnRH pulse generator and elucidate the interaction between KNDy neuropeptide signaling systems, targeting our interventions to ARC KNDy neurons. First, we investigated the effect of intra-ARC administration of the selective NK3R agonist, senktide, on pulsatile LH secretion using a frequent automated serial sampling method to obtain blood samples from freely moving ovariectomized 17β-estradiol-replaced rats. Our results show that senktide suppresses LH pulses in a dose-dependent manner. Intra-ARC administration of U50488, a selective KOR agonist, also caused a dose-dependent, albeit more modest, decrease in LH pulse frequency. Thus we tested the hypothesis that Dyn/KOR signaling localized to the ARC mediates the senktide-induced suppression of the LH pulse by profiling pulsatile LH secretion in response to senktide in rats pretreated with nor-binaltorphimine, a selective KOR antagonist. We show that nor-binaltorphimine blocks the senktide-induced suppression of pulsatile LH secretion but does not affect LH pulse frequency per se. In order to address the effects of acute activation of ARC NK3R, we quantified (using quantitative RT-PCR) changes in mRNA levels of KNDy-associated genes in hypothalamic micropunches following intra-ARC administration of senktide. Senktide down-regulated expression of genes encoding GnRH and GPR54 (GNRH1 and Kiss1r, respectively), but did not affect the expression of Kiss1 (which encodes kisspeptin). We conclude that NKB suppresses the GnRH pulse generator in a KOR-dependent fashion and regulates gene expression in GnRH neurons.

scholarly journals Definition of the hypothalamic GnRH pulse generator in mice

2017 ◽  
Vol 114 (47) ◽  
pp. E10216-E10223 ◽  
Author(s):  
Jenny Clarkson ◽  
Su Young Han ◽  
Richard Piet ◽  
Timothy McLennan ◽  
Grace M. Kane ◽  
...  
Keyword(s):  
Arcuate Nucleus ◽  
Pulse Generator ◽  
Hormone Secretion ◽  
Pulse Generation ◽  
Neuron Population ◽  
Lh Pulsatility ◽  
Freely Behaving ◽  
Definition Of ◽  
Lh Secretion

The pulsatile release of luteinizing hormone (LH) is critical for mammalian fertility. However, despite several decades of investigation, the identity of the neuronal network generating pulsatile reproductive hormone secretion remains unproven. We use here a variety of optogenetic approaches in freely behaving mice to evaluate the role of the arcuate nucleus kisspeptin (ARNKISS) neurons in LH pulse generation. Using GCaMP6 fiber photometry, we find that the ARNKISS neuron population exhibits brief (∼1 min) synchronized episodes of calcium activity occurring as frequently as every 9 min in gonadectomized mice. These ARNKISS population events were found to be near-perfectly correlated with pulsatile LH secretion. The selective optogenetic activation of ARNKISS neurons for 1 min generated pulses of LH in freely behaving mice, whereas inhibition with archaerhodopsin for 30 min suppressed LH pulsatility. Experiments aimed at resetting the activity of the ARNKISS neuron population with halorhodopsin were found to reset ongoing LH pulsatility. These observations indicate the ARNKISS neurons as the long-elusive hypothalamic pulse generator driving fertility.

scholarly journals A conceptual model of the influence of stress on female reproduction

Reproduction ◽  
2003 ◽  
pp. 151-163 ◽  
Author(s):  
H Dobson ◽  
S Ghuman ◽  
S Prabhakar ◽  
R Smith
Keyword(s):  
Neuropeptide Y ◽  
Brain Stem ◽  
Paraventricular Nucleus ◽  
Arcuate Nucleus ◽  
Preoptic Area ◽  
Pulse Frequency ◽  
Medial Preoptic Area ◽  
Aminobenzoic Acid ◽  
Female Reproduction ◽  
Cell Recruitment

Intriguingly, similar neurotransmitters and nuclei within the hypothalamus control stress and reproduction. GnRH neurone recruitment and activity is regulated by a balance between stimulation, suppression and permissiveness controlled by noradrenaline, neuropeptide Y and serotonin from the brain stem, impact from glutamate in the medial preoptic area and neuropeptide Y in the arcuate nucleus, in opposition to the restraining influences of gamma-aminobenzoic acid within the medial preoptic area and opioids from the arcuate nucleus. Stress also activates neuropeptide Y perikarya in the arcuate nucleus and brain stem noradrenaline neurones. The latter project either indirectly, via the medial preoptic area, or directly to the paraventricular nucleus to release corticotrophin releasing hormone (CRH) and arginine vasopressin (AVP). Within the medial preoptic area, GnRH neurones synapse with CRH and AVP axons. Stimulation of CRH neurones in the paraventricular nucleus also activates gamma-aminobenzoic acid and opioid neurones in the medial preoptic area and reduces GnRH cell recruitment, thereby decreasing GnRH pulse frequency. Oestradiol enhances stress-induced noradrenaline suppression of LH pulse frequency but when applied in the paraventricular nucleus or brain stem, and not in the medial preoptic area or arcuate nucleus. The importance of CRH and AVP in the medial preoptic area needs confirming in a species other than the rat, which uses adrenal activation to time the onset of the GnRH surge. Another stress-activated pathway involves the amygdala and bed of the nucleus stria terminalis, which contain CRH neurones and accumulate gamma-aminobenzoic acid during stress.

scholarly journals Novel insights into the metabolic action of Kiss1 neurons

2020 ◽  
Vol 9 (5) ◽  
pp. R124-R133 ◽  
Author(s):  
Rajae Talbi ◽  
Victor M Navarro
Keyword(s):  
Arcuate Nucleus ◽  
Pulse Generator ◽  
Experimental Models ◽  
Close Apposition ◽  
Comprehensive Overview ◽  
Regulation Of Metabolism ◽  
Gnrh Release ◽  
Recent Developments ◽  
Metabolic Action

Kiss1 neurons are essential regulators of the hypothalamic–pituitary–gonadal (HPG) axis by regulating gonadotropin-releasing hormone (GnRH) release. Compelling evidence suggests that Kiss1 neurons of the arcuate nucleus (Kiss1ARC), recently identified as the hypothalamic GnRH pulse generator driving fertility, also participate in the regulation of metabolism through kisspeptinergic and glutamatergic interactions with, at least, proopiomelanocortin (POMC) and agouti-related peptide (AgRP)/neuropeptide Y (NPY) neurons, located in close apposition with Kiss1ARC. This review offers a comprehensive overview of the recent developments, mainly derived from animal models, on the role of Kiss1 neurons in the regulation of energy balance, including food intake, energy expenditure and the influence of circadian rhythms on this role. Furthermore, the possible neuroendocrine pathways underlying this effect, and the existing controversies related to the anorexigenic action of kisspeptin in the different experimental models, are also discussed.

329. IS THERE VARIATION IN THE LEVEL OF INPUT OF KISSPEPTIN TERMINALS ONTO GnRH NEURONS ACROSS THE EQUINE OESTROUS CYCLE?

2010 ◽  
Vol 22 (9) ◽  
pp. 129
Author(s):  
C. J. Scott ◽  
C. A. Setterfield ◽  
A. Caraty ◽  
S. T. Norman
Keyword(s):  
Arcuate Nucleus ◽  
Preoptic Area ◽  
Reproductive Function ◽  
Oestrous Cycle ◽  
Gnrh Neurons ◽  
Gonadotrophin Releasing Hormone ◽  
Potential Interactions ◽  
Lh Secretion ◽  
The Brain ◽  
Dual Label

Kisspeptin (KP) plays a key role in reproductive function including the regulation of gonadotrophin releasing hormone (GnRH) and luteinising hormone (LH) secretion in many species but little is known about its role in the mare. In this study, we examined the location of KP-producing neurons in the brain of the mare, their potential interactions with GnRH neurons, and temporal changes in their expression across the oestrous cycle. Mares (n = 3/group) were killed at oestrus (just prior to ovulation), mid-dioestrus, and late dioestrus and the head was perfusion fixed with paraformaldehyde, and hypothalamus collected. Coronal sections (40 μm) were used for dual-label immuno-stained for KP & GnRH. The majority of KP-immunoreactive (-ir) neurons were located in the arcuate nucleus/median eminence (especially mid and caudal regions), and periventricular nucleus. There was a trend (P = 0.09) towards increasing numbers of KP-ir neurons across the cycle. GnRH-ir neurons, located primarily in the arcuate nucleus (especially mid arcuate), as well as the preoptic area, did not change in number across the cycle. Numerous interactions between KP and GnRH neurons were observed, primarily in the arcuate nucleus; KP fibres interacting with GnRH cell bodies, fibre-fibre interactions between KP and GnRH, and GnRH fibres interacting with KP cell bodies. Overall we found KP inputs to 32% of GnRH-ir cells, but the number of these interactions did not vary across the oestrous cycle. This study has confirmed the reciprocal innervation between KP & GnRH neurons in the mare. Although we did not detect variation in the degree across the oestrous cycle this may reflect the sample size issues inherent to equine research.

scholarly journals Prenatal Testosterone Treatment Leads to Changes in the Morphology of KNDy Neurons, Their Inputs, and Projections to GnRH Cells in Female Sheep

Endocrinology ◽  
2015 ◽  
Vol 156 (9) ◽  
pp. 3277-3291 ◽  
Author(s):  
Maria Cernea ◽  
Vasantha Padmanabhan ◽  
Robert L. Goodman ◽  
Lique M. Coolen ◽  
Michael N. Lehman
Keyword(s):  
Feedback Control ◽  
Arcuate Nucleus ◽  
Preoptic Area ◽  
Neurokinin B ◽  
Medial Basal Hypothalamus ◽  
Synaptic Inputs ◽  
Prenatal Testosterone ◽  
Peptide Expression ◽  
Kndy Neurons ◽  
Female Sheep

Prenatal testosterone (T)-treated ewes display a constellation of reproductive defects that closely mirror those seen in PCOS women, including altered hormonal feedback control of GnRH. Kisspeptin/neurokinin B/dynorphin (KNDy) neurons of the arcuate nucleus (ARC) play a key role in steroid feedback control of GnRH secretion, and prenatal T treatment in sheep causes an imbalance of KNDy peptide expression within the ARC. In the present study, we tested the hypothesis that prenatal T exposure, in addition to altering KNDy peptides, leads to changes in the morphology and synaptic inputs of this population, kisspeptin cells of the preoptic area (POA), and GnRH cells. Prenatal T treatment significantly increased the size of KNDy cell somas, whereas POA kisspeptin, GnRH, agouti-related peptide, and proopiomelanocortin neurons were each unchanged in size. Prenatal T treatment also significantly reduced the total number of synaptic inputs onto KNDy neurons and POA kisspeptin neurons; for KNDy neurons, the decrease was partly due to a decrease in KNDy-KNDy synapses, whereas KNDy inputs to POA kisspeptin cells were unaltered. Finally, prenatal T reduced the total number of inputs to GnRH cells in both the POA and medial basal hypothalamus, and this change was in part due to a decreased number of inputs from KNDy neurons. The hypertrophy of KNDy cells in prenatal T sheep resembles that seen in ARC kisspeptin cells of postmenopausal women, and together with changes in their synaptic inputs and projections to GnRH neurons, may contribute to defects in steroidal control of GnRH observed in this animal model.

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