ライフサイエンスコーパス: kisspeptin

1 RH neurons tested were activated by AMPA and kisspeptin.

2 , gonadotropin-releasing hormone (GnRH), and kisspeptin.

3 luteinizing hormone surge-mediating peptide, kisspeptin.

4 reased when slice cultures were treated with kisspeptin.

5 y components of the antimetastatic effect of kisspeptins.

6 ns opposite to that of the puberty-promoting kisspeptins.

7 ch as the initiation of sexual maturation by kisspeptins.

8 Transcriptomic profiling revealed high kisspeptin 1 (KISS1) related to reduced migration and lo

9 modifications of the endogenous neuropeptide kisspeptin 10 (KP10).

10 atile i.v. infusion of synthetic GnRH before kisspeptin-10 (112-121) injection.

11 Kisspeptin-10 (Kp-10), a decapeptide derived from the pr

12 derived from the KiSS-1 product, designated kisspeptin-10 (Kp-10), activates a receptor coupled to G

13 og) or i.v. (100 microg) bolus injections of kisspeptin-10 elicited a robust GnRH discharge, as refle

14 In contrast, kisspeptin-10 stimulated LH release after both central a

15 d previously that the activation of GPR54 by kisspeptin-10 suppressed CXCR4-mediated chemotaxis in re

16 activation of its cognate receptor GPR54 by kisspeptin-10 suppressed the capacity of the prometastat

17 we used the monkey to examine the ability of kisspeptin-10 to elicit the release of gonadotropin-rele

18 Intracerebroventricular administration of kisspeptin-10 to Vgat-Cre;Lepr(lox/lox) female mice elic

19 In vitro and in vivo studies of analogues of kisspeptin-10 with amino substitutions have identified s

20 s, resulting from the addition of its ligand Kisspeptin-10, resulted in RhoA activation and RhoA-depe

21 inistered a single subcutaneous injection of kisspeptin-54 (1.6 nmol/kg, n = 2; 3.2 nmol/kg, n = 3; 6

22 uent fertilization of eggs matured following kisspeptin-54 administration and transfer of resulting e

23 tudy demonstrates that a single injection of kisspeptin-54 can induce egg maturation in women with su

24 r ovulation; therefore, we hypothesized that kisspeptin-54 could be used to trigger egg maturation in

25 observed in response to each tested dose of kisspeptin-54, and the mean number of mature eggs per pa

26 Kisspeptin-54, the major circulating isoform of kisspept

27 yos to the uterus occurred in 92% (49/53) of kisspeptin-54-treated patients.

28 Tolson and colleagues provide evidence that kisspeptin, a hormone that promotes sexual maturation, r

29 rganization of neural projections containing kisspeptin, a key neuropeptide involved in pubertal acti

30 Kisspeptin, a neuropeptide encoded by the KISS1/Kiss1, a

31 Here we show that kisspeptin, a potent activator of GnRH neuronal activity

32 The neuropeptide kisspeptin, a potent activator of GnRH neurons that is i

33 We investigated the effects of kisspeptin, a recently identified key reproductive hormo

34 The current-voltage relationships of the kisspeptin-activated NSCC currents exhibited double rect

35 report inhibitory actions of GnIH/RFRP-3 on kisspeptin-activated vGluT2 (vesicular glutamate transpo

36 nd reproduction directly at the level of the kisspeptin-activated vGluT2-GnRH neuron.

37 In addition, kisspeptin administration attenuated negative mood.

38 We demonstrated that kisspeptin administration enhanced limbic brain activity

39 Kisspeptin administration restored gonadotropin secretio

40 4, suggesting a paracrine mechanism in which kisspeptins affect cells in the metastatic niche.

41 the pituitary cells independent from GnRH or kisspeptin and could play multiple roles in reproductive

42 hronize and shape the pulsatile secretion of kisspeptin and drive the release of GnRH from fibers in

43 capacity of GnRH neurons to be activated by kisspeptin and estradiol.

44 as a conditional relay station downstream of kisspeptin and GnIH to signal the availability of energy

45 central peptides that regulate reproduction, kisspeptin and GnIH, exert a strong direct action on POM

46 nstrate that the neural circuits between ARC kisspeptin and GnRH neurons are fully established and op

47 Kisspeptin and GPR54 are expressed in discrete regions o

48 Kisspeptin and its cognate receptor, GPR54, are critical

49 ts of the Kiss1 gene, and the interaction of kisspeptin and its receptor GPR54 plays a crucial role i

50 Hypothalamic neurons that produce kisspeptin and neurokinin B stimulate GnRH release.

51 Thus, interactions between kisspeptin and nNOS neurons may play a central role in r

52 ave demonstrated the coexpression of NKB and kisspeptin and their comodulatory roles over the control

53 examined whether GnIH inhibits the action of kisspeptin and vasoactive intestinal polypeptide (VIP),

54 hormone on the signaling pathways induced by kisspeptin and vasoactive intestinal polypeptide in GnRH

55 is a G-protein-coupled receptor, which binds kisspeptins and is widely expressed throughout the brain

56 est the presence of independent pathways for kisspeptins and NKB neurons in the brain of zebrafish.

57 acids (glutamate) and at least one peptide (kisspeptin), and by glial inputs provided by growth fact

58 neuropeptides encoded by the Kiss1 gene, the kisspeptins, and their cognate receptor, GPR54, which ha

59 These studies establish that kisspeptin antagonists are powerful investigative tools

60 We have pioneered the development of kisspeptin antagonists as powerful tools for interrogati

61 The development of kisspeptin antagonists provides a valuable tool for inve

62 We have developed kisspeptin antagonists to facilitate the direct determin

63 cells and, finally, we investigated whether kisspeptins are expressed in the pituitary gland.

64 Kisspeptins are neuropeptides encoded by the Kiss1 gene,

65 Kisspeptins are now considered key players in the neuroe

66 Kisspeptins are potent secretagogues for GnRH, and the K

67 Kisspeptins are products of the Kiss1 gene, and the inte

68 to evaluate the role of the arcuate nucleus kisspeptin (ARN(KISS)) neurons in LH pulse generation.

69 o the current pharmacological development of kisspeptin as a potential therapeutic agent for patients

70 Kisspeptin binds to its cognate receptor on GnRH neurons

71 A second subpopulation is insensitive to kisspeptin but is uniquely activated by group I metabotr

72 tion of kisspeptin mRNA (Kiss1) and protein (kisspeptin) by using in situ hybridization, real-time PC

73 NMDA and kisspeptins can stimulate gonadotropin-releasing hormone

74 Initially, we cloned a guinea pig kisspeptin cDNA sequence and subsequently explored the d

75 Deletion of ERalpha in kisspeptin cells decreased glutamate transmission to AVP

76 E2 reduced the number of immunoreactive kisspeptin cells in the PV at both time points, perhaps

77 These observations indicate that ERalpha in kisspeptin cells is required for appropriate differentia

78 a knock-out mice demonstrate that ERalpha in kisspeptin cells is required for appropriate differentia

79 ack may reflect a complex interaction of the kisspeptin circuitry, and both the PV and the Arc respon

80 These actions of kisspeptin contribute to the pronounced excitation of Gn

81 inhibitory feedback, it is required for the kisspeptin-dependent preovulatory activation of GnRH neu

82 kisspeptin-independent) and nerve terminals (kisspeptin-dependent) in a dual way to participate in th

83 Presently, we found that kisspeptin depolarized GnRH neurons in a concentration-d

84 Therefore, it appears that kisspeptin depolarizes GnRH neurons through activating T

85 ally dimorphic, with females possessing more kisspeptin, dopaminergic, and GABA/glutamate neurons tha

86 n of the G-protein-coupled receptor GPR54 by kisspeptins during normal puberty promotes the central r

87 ns are steroid-responsive and coexpress NKB, kisspeptin, dynorphin, NK3R, and estrogen receptor alpha

88 mework to explain how coordination among NKB/kisspeptin/dynorphin/NK3R/ERalpha neurons could mediate

89 We have recently identified two kisspeptin-encoding genes, kiss1 and kiss2, in teleosts.

90 yrus, and in a previous study we showed that kisspeptin enhances excitatory synaptic transmission in

91 secretion is mediated by its receptor in the kisspeptin enriched hypothalamic AVPV and ARC respective

92 contrast, brief exposure to the neuropeptide kisspeptin-evoked long-lasting Ca(2+) plateaus that pers

93 cells, inhibit POMC cells and attenuate the kisspeptin excitation by a mechanism based on opening po

94 established, composed of two populations of kisspeptin-expressing neurons (located in the anterovent

95 H and gonadotropin secretion, and diminished kisspeptin expression.

96 ), which are morphologically associated with kisspeptin fibers, express the kisspeptin receptor GPR54

97 Moreover, the kisspeptin gene (Kiss1) was recently identified in the a

98 We have previously identified two kisspeptin genes (kiss1 and kiss2) in the zebrafish, of

99 ined the coexpression of tachykinins and two kisspeptin genes in the brain of zebrafish.

100 hysiological recordings in brain slices from kisspeptin-GFP mice showed that AVP dose-dependently inc

101 riectomized (OVX), diestrous, and proestrous kisspeptin-GFP mice.

102 Kisspeptin-GPR54 signaling has been implicated in the re

103 This review discusses the latest ideas about kisspeptin-GPR54 signaling in the neuroendocrine regulat

104 cle in rodents; however, the precise role of kisspeptin-GPR54 signaling in the regulation of gonadotr

105 We also postulated that kisspeptin-GPR54 signaling is critical for the generatio

106 knock-out (KO) mice, we first tested whether kisspeptin-GPR54 signaling is necessary for male and fem

107 Our findings indicate that kisspeptin-GPR54 signaling is not required for male or f

108 Thus, in mice, kisspeptin-GPR54 signaling is required for the tonic sti

109 nock-outs (KOs)] to test the hypothesis that kisspeptin-GPR54 signaling provides the drive necessary

110 Other reproductive roles for kisspeptin-GPR54 signaling, including the regulation of

111 nRH secretion is disrupted in the absence of kisspeptin-GPR54 signaling.

112 and peripheral tissues, which suggests that kisspeptin has additional functions beyond reproduction.

113 Although kisspeptin has been found to depolarize GnRH neurons, th

114 Kisspeptin has recently been identified as a key neuroen

115 r, such relationship between tachykinins and kisspeptins has not been demonstrated in non-mammalian s

116 fied plasma gonadal steroids and GnRH-1- and kisspeptin-immunoreactive (ir) neurons in subordinate ad

117 Within the Arc, the kisspeptin immunoreactivity was decreased during negativ

118 These demonstrate an essential role for kisspeptin in GnRH neuron firing, GnRH pulsatile secreti

119 speptin-54, the major circulating isoform of kisspeptin in humans, potently stimulates reproductive h

120 provide evidence of an undescribed role for kisspeptin in integrating sexual and emotional brain pro

121 monkeys; the later supporting a key role of kisspeptin in puberty onset.

122 powerful tools for interrogating the role of kisspeptin in reproductive physiology and pathology, and

123 in the system's regulation, and opioids and kisspeptin in the medial preoptic area (mPOA) and hypoth

124 th special emphasis on the role of Kiss1 and kisspeptin in the negative and positive feedback control

125 hysiological and pathophysiological roles of kisspeptin in the regulation of reproduction and could o

126 in regulating energy balance and of GnRH and kisspeptin in triggering puberty and maintaining fertili

127 As a first step in investigating the role of kisspeptins in the European sea bass, a perciform fish,

128 Kisspeptin increased GnRH excitability and was essential

129 Kisspeptin increased GnRH neuron response in cells from

130 alamus of mutant mice, indicating a possible kisspeptin-independent GnRH/LH release by NMDA through a

131 Thus, NMDA may act at both GnRH cell bodies (kisspeptin-independent) and nerve terminals (kisspeptin-

132 Under voltage-clamp conditions, kisspeptin induced an inward current of 18.2 +/- 1.6 pA

133 ent mechanism and could prevent or interrupt kisspeptin-induced activation of vGluT2-GnRH neurons.

134 r Na(+) (to 5 mM) essentially eliminated the kisspeptin-induced inward current.

135 Pharmacological examination showed that the kisspeptin-induced inward currents were blocked by TRPC

136 This analog also inhibited the kisspeptin-induced release of luteinizing hormone (LH) i

137 In contrast, kisspeptin inhibits orexigenic neuropeptide Y (NPY) neur

138 were retrieved transvaginally 36 hours after kisspeptin injection, assessed for maturation (primary o

139 Here, we show strong kisspeptin innervation of hypothalamic anorexigenic proo

140 ain sexual differentiation and indicate that kisspeptin inputs to GnRH neurons are essential for this

141 The importance of kisspeptin inputs to GnRH neurons for the process of sex

142 te transporter 2)-GnRH neurons as well as on kisspeptin-insensitive GnRH neurons, but not on choliner

143 MCH has no effect on kisspeptin-insensitive GnRH, vGluT2, cholinergic, or GAB

144 r presence of gonads, substantial numbers of kisspeptin-ir cell bodies are detected in the rostral pe

145 previously investigated species, numbers of kisspeptin-ir cell bodies vary from substantial to negli

146 As in phylogenetically related guinea pigs, kisspeptin-ir processes pervade the internal and externa

147 Kisspeptin is a C-terminally amidated peptide encoded by

148 Kisspeptin is a product of the Kiss1 gene and is express

149 e most potent stimulator of GnRH/LH release, kisspeptin is believed to mediate the positive and negat

150 Kisspeptin is encoded by the Kiss1 gene, and kisspeptin

151 Kisspeptin is essential for reproductive functions in hu

152 rtal progression, indicating that functional kisspeptin is important for puberty and reproduction in

153 Animal studies suggest that kisspeptin is involved in generation of the luteinizing

154 The neuropeptide kisspeptin is necessary for reproduction, fertility, and

155 ature of the cellular target of the secreted kisspeptins is unknown.

156 Kisspeptins (Kiss) have been shown to be key components

157 The kisspeptin (Kiss1) and Kiss1 receptor (Kiss1r) pathway p

158 Kisspeptin (Kiss1) and neurokinin B (NKB) neurocircuits

159 t rodents is sex specific and dependent upon kisspeptin (Kiss1) neurons.

160 ociated or coexpressed with GnRH1, GnRH3, or kisspeptin (Kiss2) neurons.

161 cy GnRH release was similar in wild-type and kisspeptin knock-out mice indicating that this release i

162 Paradoxically, excitability in kisspeptin knock-out mice was similar to the maximum obs

163 RH) is the master regulator of fertility and kisspeptin (KP) is a potent trigger of GnRH secretion fr

164 However, human kisspeptin loss-of-function mutations have not been desc

165 neuronal activity and activation of GPR54 by kisspeptin may in turn contribute to sustain basal BDNF

166 Our studies indicate that administration of kisspeptin may serve as an alternative therapeutic appro

167 tatory response by POMC neurons (n > 200) to kisspeptin, mediated by mechanisms based on activation o

168 dicating that this release is independent of kisspeptin-mediated excitation.

169 neurons leads to a significant reduction in kisspeptin-mediated GnRH neuronal activity.

170 tion and 17beta-estradiol (E2) regulation of kisspeptin mRNA (Kiss1) and protein (kisspeptin) by usin

171 wed no coexpression of tachykinins mRNA with kisspeptins mRNA in hypothalamic nuclei or the habenula.

172 panied by marked alterations in hypothalamic kisspeptin/neurokinin B/dynorphin (KNDy) neurons, we hyp

173 In both kisspeptin neuron populations from OVX mice, the frequen

174 These actions were mediated directly at the kisspeptin neuron.

175 rate that synchronized activation of the ARN kisspeptin neuronal population generates pulses of LH.

176 s that in guinea pig both the PV and the Arc kisspeptin neurons act cooperatively to excite gonadotro

177 his strategy targeted ChR2 to 70% of all ARN kisspeptin neurons and that, in vitro, these neurons wer

178 Kisspeptin neurons appear to be integrative sensors, as

179 We demonstrate that a population of kisspeptin neurons appears in the preoptic area of only

180 We show that ARC kisspeptin neurons are upstream of GnRH neurons, and tha

181 In vivo, the optogenetic activation of ARN kisspeptin neurons at 10 and 20 Hz evoked high amplitude

182 ns, and that GnRH neuron connectivity to ARC kisspeptin neurons does not depend on their spatial posi

183 e expressing the calcium indicator GCaMP3 in kisspeptin neurons enabled simultaneous monitoring of in

184 RP3V kisspeptin neurons exhibited marked changes in the hyper

185 Whereas <25% of preoptic kisspeptin neurons expressed Cre in Vgat- and Vglut2-ire

186 Kisspeptin neurons have recently been identified to be p

187 n steroids as AVP no longer excited preoptic kisspeptin neurons in ovariectomized mice, an effect tha

188 ressing afferents of GnRH neurons, including kisspeptin neurons in the anteroventral periventricular

189 by NKB and dynorphin act autosynaptically on kisspeptin neurons in the Arc to synchronize and shape t

190 eedback (estrogen receptor alpha [ERalpha]); kisspeptin neurons in the arcuate and anteroventral peri

191 In rodents, kisspeptin neurons in the arcuate nucleus (Arc) provide

192 he sexual differentiation and development of kisspeptin neurons in the AVPV is mediated by developmen

193 Kisspeptin neurons in the hypothalamic arcuate nucleus (

194 tate the direct determination of the role of kisspeptin neurons in the neuroendocrine regulation of r

195 hough recent studies have suggested that the kisspeptin neurons located in the arcuate nucleus (ARN)

196 nadal steroids modulated the excitability of kisspeptin neurons located in the rostral periventricula

197 asticity in the intrinsic properties of RP3V kisspeptin neurons may contribute to the generation of t

198 LH in sheep, rats, and mice, suggesting that kisspeptin neurons mediate the negative feedback effect

199 Kisspeptin neurons of the arcuate nucleus and anterovent

200 etion and ovarian cyclicity, suggesting that kisspeptin neurons play a major role in hyperprolactinem

201 o permit circadian AVP signaling at preoptic kisspeptin neurons rather than dynamically modulate its

202 l neuropeptide underlying the ability of ARN kisspeptin neurons to generate LH pulses.

203 AVP increased [Ca(2+)]i in >80% of diestrous kisspeptin neurons via a mechanism involving voltage-gat

204 naptic mechanisms to differentially regulate kisspeptin neurons via GABAergic transmission.

205 We next examined whether AVP signaling in kisspeptin neurons was time and ovarian cycle dependent.

206 d mice, 5-, 10-, and 20-Hz activation of ARN kisspeptin neurons were all found to evoke LH pulses.

207 ires-Cre lines, approximately 70% of arcuate kisspeptin neurons were targeted in Vglut2-ires-Cre;Esr1

208 In arcuate, but not AVPV, kisspeptin neurons, estradiol reduced miniature postsyna

209 GABA hyperpolarized AVPV kisspeptin neurons, except in the OVX PM group in which

210 neurons and markedly increased it to arcuate kisspeptin neurons, which also exhibited increased spont

211 Kisspeptin neurons, which express prolactin receptors, w

212 tradiol-dependent increase in Ih within RP3V kisspeptin neurons.

213 ulating the spontaneous burst firing of RP3V kisspeptin neurons.

214 essin (AVP) on the activity of preoptic area kisspeptin neurons.

215 ependently increased the firing rate of most kisspeptin neurons.

216 ical activity and [Ca(2+)]i of most preoptic kisspeptin neurons.

217 ns using transgenic mice with GFP-identified kisspeptin neurons.

218 least in part through modulatory effects on kisspeptin neurons.

219 smission to AVPV and increased it to arcuate kisspeptin neurons; positive feedback had the opposite e

220 icantly suppressed the stimulatory effect of kisspeptin on GnRH release in hypothalamic culture, GnIH

221 The excitatory actions of kisspeptin on POMC cells were corroborated with quantita

222 rtantly, MCH blocks the excitatory effect of kisspeptin on vGluT2-GnRH neurons.

223 ic neuronal populations in the AVPV, such as kisspeptin or dopaminergic neurons.

224 his study provides a direct link between the kisspeptin pathway and metabolic output, more work will

225 expressed channelrhodopsin (ChR2) in the ARN kisspeptin population to test directly whether synchrono

226 ing that glutamatergic transmission to these kisspeptin populations is differentially regulated durin

227 We find that kisspeptin-producing neurons in the arcuate nucleus (ARC

228 rons are regulated by an afferent network of kisspeptin-producing neurons.

229 on, but it does not result in alterations in kisspeptin projections.

230 matostatin receptors 1 and 2 (SSTR1, SSTR2), kisspeptin recepotor (KissR1), neurotensin receptor 1 (N

231 Female mice lacking the kisspeptin receptor (KISS1R) gained more weight than con

232 Here, we show that the kisspeptin receptor (Kiss1r), a GPCR that is activated b

233 ng mutations in the genes encoding the human kisspeptin receptor (KISS1R, formerly called GPR54), neu

234 e attenuation of excitation by the selective kisspeptin receptor antagonist, peptide 234.

235 roborated with quantitative PCR data showing kisspeptin receptor GPR54 expression in the arcuate nucl

236 sociated with kisspeptin fibers, express the kisspeptin receptor GPR54 in the preoptic region, but no

237 , we find that most GnRH neurons express the kisspeptin receptor GPR54 upon circuit formation, sugges

238 pin-releasing hormone (GnRH) neurons via the kisspeptin receptor KISS1R.

239 al differentiation of male mice in which the kisspeptin receptor was deleted selectively from GnRH ne

240 s cognate G protein-coupled receptor, GPR54 (kisspeptin receptor, Kiss-R), are critical for the contr

241 Experiments in kisspeptin receptor-null mice, showed that kisspeptin wa

242 The neuropeptide kisspeptin regulates reproduction by stimulating gonadot

243 1 receptor (KISS1R or GPR54) by its ligands (Kisspeptins) regulates a diverse function both in normal

244 uate nucleus (ARC), all regions critical for kisspeptin regulation of gonadotropin secretion.

245 pogonadotrophic state in females may involve kisspeptin-related mechanisms similar to those underlyin

246 luciferase (LUC) reporter gene localized at kisspeptin-response element (KsRE) between -3446 and -28

247 Furthermore, kisspeptin's enhancement of limbic brain structures corr

248 etic and metabolic phenotype in mice lacking kisspeptin signaling (Kiss1r KO mice).

249 Patients with mutations that inactivate kisspeptin signaling are infertile.

250 the hypothalamus to suppress the vasopressin-kisspeptin signaling cascade, thereby inhibiting the pro

251 iss1(-/-) mice and by genetic restoration of kisspeptin signaling in GnRH neurons in Kiss1r(-/-) mice

252 ndicating that GnIH may not directly inhibit kisspeptin signaling in GnRH neurons.

253 The activation of kisspeptin signaling in preoptic neurons promotes the ac

254 the contributions of central and peripheral kisspeptin signaling in regulating uterine growth and ad

255 emonstrate that in addition to reproduction, kisspeptin signaling influences BW, energy expenditure,

256 via central kisspeptin signaling, peripheral kisspeptin signaling is indispensable for endometrial ad

257 ndependent manner; therefore, alterations in kisspeptin signaling might contribute, directly or indir

258 s in organizing the sex-specific ontogeny of kisspeptin signaling pathways remain unresolved.

259 Kisspeptin is encoded by the Kiss1 gene, and kisspeptin signaling plays a critical role in reproducti

260 y dependent on ovarian E2-output via central kisspeptin signaling, peripheral kisspeptin signaling is

261 l and in vivo hormone profile experiments on kisspeptin-specific ERalpha knock-out mice demonstrate t

262 ic culture, GnIH had no inhibitory effect on kisspeptin stimulation of serum response element and nuc

263 asis for a paracrine mode of action by which kisspeptins suppress the metastatic potential of tumor c

264 experiment 2, using microdialysis, GnRH and kisspeptin surges induced by E2 benzoate were similarly

265 se AVPV populations, the recently identified kisspeptin system has been most strongly implicated as a

266 de an insight into the role of the habenular kisspeptin system in inhibiting fear.

267 The Kiss1 gene produces kisspeptins that stimulate GnRH secretion.

268 tly achieving an increased responsiveness to kisspeptin, the main secretagogue of GnRH.

269 ceptor (Kiss1r), a GPCR that is activated by kisspeptin to regulate the onset of puberty and adult re

270 ometric analyses, we compared the effects of kisspeptin versus vehicle administration in 29 healthy h

271 n kisspeptin receptor-null mice, showed that kisspeptin was the critical neuropeptide underlying the

272 or agonists, but is exquisitely sensitive to kisspeptin which closes potassium channels to dramatical

273 The Kiss1 gene codes for kisspeptin, which binds to GPR54, a G-protein-coupled re

274 Kisspeptin, which signals via Kiss1r, is essential for f