Neurokinin B and dynorphin A in kisspeptin neurons of the arcuate nucleus participate in generation of periodic oscillation of neural activity driving pulsatile gonadotropin-releasing hormone secretion in the goat
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Gonadotropin-releasing hormone (GnRH) neurons in the basal forebrain are the final common pathway through which the brain regulates reproduction. GnRH secretion occurs in a pulsatile manner, and indirect evidence suggests the kisspeptin neurons in the arcuate nucleus (ARC) serve as the central pacemaker that drives pulsatile GnRH secretion. The purpose of this study was to investigate the possible coexpression of kisspeptin, neurokinin B (NKB), and dynorphin A (Dyn) in neurons of the ARC of the goat and evaluate their potential roles in generating GnRH pulses. Using double and triple labeling, we confirmed that all three neuropeptides are coexpressed in the same population of neurons. Using electrophysiological techniques to record multiple-unit activity (MUA) in the medial basal hypothalamus, we found that bursts of MUA occurred at regular intervals in ovariectomized animals and that these repetitive bursts (volleys) were invariably associated with discrete pulses of luteinizing hormone (LH) (and by inference GnRH). Moreover, the frequency of MUA volleys was reduced by gonadal steroids, suggesting that the volleys reflect the rhythmic discharge of steroid-sensitive neurons that regulate GnRH secretion. Finally, we observed that central administration of Dyn-inhibit MUA volleys and pulsatile LH secretion, whereas NKB induced MUA volleys. These observations are consistent with the hypothesis that kisspeptin neurons in the ARC drive pulsatile GnRH and LH secretion, and suggest that NKB and Dyn expressed in those neurons are involved in the process of generating the rhythmic discharge of kisspeptin.
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KNDy neurons could also be involved in the generation of flushes.
“Emerging evidence that KNDy neurons are an important part of the GnRH pulse generator (Lehman et al., 2010; Rance et al., 2010; Wakabayashi et al., 2010) strongly supports the hypothesis that they could also be involved in the generation of flushes.”
From Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes (2013) · cites this paper as Wakabayashi et al., 2010
KNDy neurons are an important part of the GnRH pulse generator.
“Emerging evidence that KNDy neurons are an important part of the GnRH pulse generator (Lehman et al., 2010; Rance et al., 2010; Wakabayashi et al., 2010) strongly supports the hypothesis that they could also be involved in the generation of flushes.”
From Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes (2013) · cites this paper as Wakabayashi et al., 2010
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Cites
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Knobil, E. (1980) · Elsevier eBooks · doi:10.1016/b978-0-12-571136-4.50008-5 · Cited by 1,285 · cited 1× · see citing works
“The pulsatile release of gonadotropin-releasing hormone (GnRH) is a prerequisite for sustaining normal gonadotropin secretion in mammals (Knobil, 1980; Karsch, 1984); however, the cellular and molecular mechanisms that generate the rhythmic discharge of GnRH are unknown.”
BackgroundAlgorithms for the study of episodic hormone secretion
Merriam, G. R., & Wachter, K. W. (1982) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1982.243.4.e310 · Cited by 1,221 · cited 1× · see citing works
“LH pulses were identified by the PULSAR computer program (Merriam and Wachter, 1982).”
MethodAdvances in Male Contraception
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Regulation of Kiss1 gene expression in the brain of the female mouse
Smith, J. T., Cunningham, M. J., Rissman, E. F., Clifton, D. K., & Steiner, R. A. (2005) · Endocrinology · doi:10.1210/en.2005-0488 · Cited by 1,102 · cited 1× · see citing works
“Finally, kisspeptin/ NKB/Dyn neurons in the ARC have been proposed to be a primary site of negative feedback action of E2 and P (Smith et al., 2005a,b, 2007; Burke et al., 2006; Foradori et al., 2006; Goodman et al., 2007), and we demonstrated here that E2 and P suppress the occurrence of MUA…”
BackgroundSelf-citationHan, S.-K., Gottsch, M. L., Lee, K. J., Popa, S. M., Smith, J. T., Jakawich, S. K., Clifton, D. K., Steiner, R. A., & Herbison, A. E. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.3328-05.2005 · Cited by 1,036 · cited 2× · see citing works
“duces a prolonged activation of GnRH neurons in the mouse (Han et al., 2005; Pielecka-Fortuna et al., 2008).”
BackgroundResultTopaloglu, A. K., Reimann, F., Guclu, M., Yalin, A. S., Kotan, L. D., Porter, K. M., Serin, A., Mungan, N. O., Cook, J. R., Ozbek, M. N., et al. (2009) · Nature Genetics · doi:10.1038/ng.306 · Cited by 961 · cited 2× · see citing works
“Indeed, Topaloglu et al. (2009) have recently shown that mutations of either Trc3 or Tacr3, which encode NKB and NK3, respectively, produce gonadotropin deficiency and pubertal failure in humans.”
BackgroundUse of cryoprotectant to maintain long-term peptide immunoreactivity and tissue morphology
Watson, R. E., Wiegand, S. J., Clough, R. W., & Hoffman, G. E. (1986) · Peptides · doi:10.1016/0196-9781(86)90076-8 · Cited by 933 · see citing works
Kisspeptin Signaling in the Brain
Oakley, A. E., Clifton, D. K., & Steiner, R. A. (2009) · Endocrine Reviews · doi:10.1210/er.2009-0005 · Cited by 842 · cited 1× · see citing works
“Kisspeptin neurons in the hypothalamus play a key role in the regulation of GnRH neurons (Oakley et al., 2009), but the precise nature of the interaction between kisspeptin and GnRH neurons is just emerging.”
BackgroundNavarro, V. M., Gottsch, M. L., Chavkin, C., Okamura, H., Clifton, D. K., & Steiner, R. A. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.1569-09.2009 · Cited by 779 · cited 19× · see citing works
“Finally, we tested the hypothesis that NKB and Dyn play crucial roles in driving GnRH pulse generator activity by analyzing the effects of centrally administered NKB, Dyn, and a KOR antagonist on pulsatile MUA and LH secretion.”
BackgroundResultInfluentialDifferential Regulation of KiSS-1 mRNA Expression by Sex Steroids in the Brain of the Male Mouse
Smith, J. T., Lemko, H. M. D., Stoll, E. A., Gottsch, M. L., Braun, R. E., Eacker, S. M., Clifton, D. K., & Steiner, R. A. (2005) · Endocrinology · doi:10.1210/en.2005-0323 · Cited by 694 · cited 1× · see citing works
“Finally, kisspeptin/ NKB/Dyn neurons in the ARC have been proposed to be a primary site of negative feedback action of E2 and P (Smith et al., 2005a,b, 2007; Burke et al., 2006; Foradori et al., 2006; Goodman et al., 2007), and we demonstrated here that E2 and P suppress the occurrence of MUA…”
BackgroundKisspeptin neurons in the arcuate nucleus of the ewe express both dynorphin A and neurokinin B
Goodman, R. L., Lehman, M. N., Smith, J. T., Coolen, L. M., de Oliveira, C. V. R., Jafarzadehshirazi, M. R., Pereira, A., Iqbal, J., Caraty, A., Ciofi, P., et al. (2007) · Endocrinology · doi:10.1210/en.2007-0961 · Cited by 692 · cited 12× · see citing works
“A vehicle injection was performed in each of the three treatment groups: OVX (n 7), OVX-plus-E2-treated (n 4), and OVX-plus-E2plus-P-treated (n 4), and these data served as the reference control for both the NKB and Dyn experiments.”
BackgroundResultInfluentialSmith, J. T., Clay, C. M., Caraty, A., & Clarke, I. J. (2007) · Endocrinology · doi:10.1210/en.2006-1435 · Cited by 404 · see citing works
Roseweir, A. K., Kauffman, A. S., Smith, J. T., Guerriero, K. A., Morgan, K., Pielecka-Fortuna, J., Pineda, R., Gottsch, M. L., Tena-Sempere, M., Moenter, S. M., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5740-08.2009 · Cited by 379 · cited 2× · see citing works
“Moreover, Roseweir et al. (2009) have demonstrated in several species that a kisspeptin antagonist blocks pulsatile GnRH/luteinizinghormone(LH)secretion.”
BackgroundPielecka-Fortuna, J., Chu, Z., & Moenter, S. M. (2007) · Endocrinology · doi:10.1210/en.2007-1365 · Cited by 341 · cited 2× · see citing works
“duces a prolonged activation of GnRH neurons in the mouse (Han et al., 2005; Pielecka-Fortuna et al., 2008).”
BackgroundResultBurke, M. C., Letts, P. A., Krajewski, S. J., & Rance, N. E. (2006) · Journal of Comparative Neurology · doi:10.1002/cne.21086 · Cited by 280 · cited 9× · see citing works
“A similar dense plexus of NKB/Dyn fibers has been reported in the ARC of the rat and sheep (Burke et al., 2006; Foradori et al., 2006), and an electron microscopic study in the sheep revealed that Dyn neurons in the ARC receive synaptic contact with Dyn fibers (Foradori et al.”
BackgroundResultInfluentialRamaswamy, S., Guerriero, K. A., Gibbs, R. B., & Plant, T. M. (2008) · Endocrinology · doi:10.1210/en.2008-0438 · Cited by 279 · cited 2× · see citing works
“DOI:10.1523/JNEUROSCI.5848-09.2010 Copyright © 2010 the authors 0270-6474/10/303124-09$15.00/0 the ME (Ramaswamy et al., 2008).”
BackgroundInfluentialKeen, K. L., Wegner, F. H., Bloom, S. R., Ghatei, M. A., & Terasawa, E. (2008) · Endocrinology · doi:10.1210/en.2008-0231 · Cited by 273 · see citing works
Goodman, R. L., Coolen, L. M., Anderson, G. M., Hardy, S. L., Valent, M., Connors, J. M., Fitzgerald, M. E., & Lehman, M. N. (2004) · Endocrinology · doi:10.1210/en.2003-1305 · Cited by 251 · cited 2× · see citing works
“…of either an NKB receptor (NK3) agonist or a Dyn receptor [the -opiate receptor (KOR)] antagonist profoundly influences GnRH/LH secretion (Goodman et al., 2004; SandovalGuzmán and Rance, 2004); moreover, mutations in either Trc3 or Tacr3 (which encode NKB and NK3, respectively) cause…”
BackgroundRance, N. E. (2009) · Peptides · doi:10.1016/j.peptides.2008.05.016 · Cited by 237 · cited 2× · see citing works
“These anatomical observations suggest that kisspeptin/NKB/Dyn neurons in the ARC comprise an oscillatory feedback loop interconnected through collaterals that synchronize their activity, as previously proposed (Burke et al., 2006; Foradori et al., 2006; Rance, 2009; Navarro et al., 2009).”
BackgroundSeminara, S. B., DiPietro, M. J., Ramaswamy, S., Crowley, W. F., & Plant, T. M. (2006) · Endocrinology · doi:10.1210/en.2005-1550 · Cited by 232 · cited 1× · see citing works
“Indeed, it has been reported that continuous administration of either kisspeptin (Seminara et al., 2006) or GnRH (Belchetz et al., 1978) results in reduced LH secretion.”
BackgroundGonadotrophin‐Releasing Hormone Pulse Generator Activity in the Hypothalamus of the Goat
Ohkura, S., Takase, K., Matsuyama, S., Mogi, K., Ichimaru, T., Wakabayashi, Y., Uenoyama, Y., Mori, Y., Steiner, R. A., Tsukamura, H., et al. (2009) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2009.01909.x · Cited by 210 · cited 7× · see citing works
“Double labeling of mRNA and proteins on the same section was performed as previously described (Wakabayashi et al., 2007; Ohkura et al., 2009).”
MethodResultInfluentialKrajewski, S. J., Anderson, M. J., Iles‐Shih, L., Chen, K. J., Urbanski, H. F., & Rance, N. E. (2005) · The Journal of Comparative Neurology · doi:10.1002/cne.20626 · Cited by 197 · cited 1× · see citing works
“Another possibility is that, in addition to activating kisspeptin neurons, NKB also acts on NKB receptors on GnRH nerve terminals in the ME (Krajewski et al., 2005) to inhibit GnRH secretion, perhaps through a Gi-coupled mechanism (Laniyonu et al., 1988).”
BackgroundSandoval‐Guzmán, T., & Rance, N. E. (2004) · Brain Research · doi:10.1016/j.brainres.2004.08.026 · Cited by 168 · cited 2× · see citing works
“Third, the administration of NKB to the OVX goat increased MUA but decreased LH secretion, which is consistent with previous observations that an NK3 agonist inhibits LH release in rats and mice (Sandoval-Guzmán and Rance, 2004; Navarro et al., 2009).”
ResultForadori, C. D., Coolen, L. M., Fitzgerald, M. E., Skinner, D. C., Goodman, R. L., & Lehman, M. N. (2002) · Endocrinology · doi:10.1210/en.2002-220586 · Cited by 149 · cited 1× · see citing works
“, 2006), and an electron microscopic study in the sheep revealed that Dyn neurons in the ARC receive synaptic contact with Dyn fibers (Foradori et al., 2002).”
BackgroundMori, Y., & Kano, Y. (1984) · Reproduction · doi:10.1530/jrf.0.0720223 · Cited by 128 · cited 2× · see citing works
“LH concentrations in single aliquots of 50 l plasma sample were measured by a double-antibody radioimmunoassay (Mori and Kano, 1984) with rabbit anti-ovine LH serum (Ohkura et al., 2004) and expressed in terms of ovine LH standard (NIDDK-oLH-I-4).”
MethodMori, Y., Nishihara, M., TANAKA, T., Shimizu, T., Yamaguchi, M., Takeuchi, Y., & HOSHINO, K. (2008) · Neuroendocrinology · doi:10.1159/000125746 · Cited by 128 · cited 2× · see citing works
“MUA recording and blood sampling MUA was recorded as previously described (Mori et al., 1991; Ichimaru et al., 2001; Ohkura et al., 2009) with a slight modification.”
MethodForadori, C. D., Amstalden, M., Goodman, R. L., & Lehman, M. N. (2006) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2006.01445.x · Cited by 126 · cited 7× · see citing works
“A similar dense plexus of NKB/Dyn fibers has been reported in the ARC of the rat and sheep (Burke et al., 2006; Foradori et al., 2006), and an electron microscopic study in the sheep revealed that Dyn neurons in the ARC receive synaptic contact with Dyn fibers (Foradori et al.”
BackgroundResultInfluentialNeurokinin B Gene Expression Is Increased in the Arcuate Nucleus of Ovariectomized Rats
Rance, N. E., & Bruce, T. R. (2008) · Neuroendocrinology · doi:10.1159/000126768 · Cited by 123 · cited 1× · see citing works
“Rising levels of E2 would reduce the stimulatory drive of NKB/NK3 signaling in ARC kisspeptin/NKB/Dyn neurons by suppressing the expression of NKB (Rance and Bruce, 1994; Dellovade and Merchenthaler, 2004; Navarro et al., 2009) as well as NK3 (Navarro et al., 2009), which would reduce…”
BackgroundTakase, K., Uenoyama, Y., Inoue, N., Matsui, H., Yamada, S., Shimizu, M., Homma, T., Tomikawa, J., Kanda, S., Matsumoto, H., et al. (2009) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2009.01868.x · Cited by 123 · cited 2× · see citing works
“…for 1 h. Sections were then incubated with a solution containing a monoclonal antibody to kisspeptin (1:4000; Takeda; no. 254) (Ohkura et al., 2009; Takase et al., 2009) and either a polyclonal antibody to NKB (1:4000; Peninsula Laboratories) or Dyn (1:4000; Phoenix Pharmaceuticals) in PBST-BSA…”
BackgroundMethodRetrograde Opioid Signaling Regulates Glutamatergic Transmission in the Hypothalamus
Iremonger, K. J., & Bains, J. S. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0381-09.2009 · Cited by 89 · cited 2× · see citing works
“Furthermore, it has been suggested that Dyn/KOR expressed in vasopressin neurons modulates the phasic firing of those neurons and the release of vasopressin by an autosynaptic loop (Brown et al., 1998; Iremonger and Bains, 2009).”
Backgroundκ-Opioid Regulation of Neuronal Activity in the Rat Supraoptic NucleusIn Vivo
Brown, C. H., Ludwig, M., & Leng, G. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-22-09480.1998 · Cited by 76 · cited 1× · see citing works
“Furthermore, it has been suggested that Dyn/KOR expressed in vasopressin neurons modulates the phasic firing of those neurons and the release of vasopressin by an autosynaptic loop (Brown et al., 1998; Iremonger and Bains, 2009).”
BackgroundDellovade, T., & Merchenthaler, I. J. (2003) · Endocrinology · doi:10.1210/en.2003-0894 · Cited by 74 · cited 1× · see citing works
“…reduce the stimulatory drive of NKB/NK3 signaling in ARC kisspeptin/NKB/Dyn neurons by suppressing the expression of NKB (Rance and Bruce, 1994; Dellovade and Merchenthaler, 2004; Navarro et al., 2009) as well as NK3 (Navarro et al., 2009), which would reduce kisspeptin/NKB/Dyn (MUA) burst…”
BackgroundNalivaiko, E., Michaud, J. C., Soubrié, P., Fur, G. L., & FELTZ, P. (1997) · Neuroscience · doi:10.1016/s0306-4522(96)00625-2 · Cited by 66 · cited 1× · see citing works
“For example, activation of NK3 increases firing in noradrenergic and dopaminergic neurons (Jung et al., 1996; Nalivaiko et al., 1997), whereas NK3 antagonists attenuate pharmacologically induced firing of dopaminergic neurons (Gueudet et al., 1999).”
BackgroundOhkura, S., Ichimaru, T., Itoh, F., Matsuyama, S., & Okamura, H. (2004) · Endocrinology · doi:10.1210/en.2003-1516 · Cited by 54 · cited 2× · see citing works
“LH concentrations in single aliquots of 50 l plasma sample were measured by a double-antibody radioimmunoassay (Mori and Kano, 1984) with rabbit anti-ovine LH serum (Ohkura et al., 2004) and expressed in terms of ovine LH standard (NIDDK-oLH-I-4).”
BackgroundMethodLaniyonu, A. A., Sliwinski-Lis, E., & Fleming, N. (1988) · FEBS Letters · doi:10.1016/0014-5793(88)80365-x · Cited by 52 · cited 1× · see citing works
“Another possibility is that, in addition to activating kisspeptin neurons, NKB also acts on NKB receptors on GnRH nerve terminals in the ME (Krajewski et al., 2005) to inhibit GnRH secretion, perhaps through a Gi-coupled mechanism (Laniyonu et al., 1988).”
BackgroundThe hypothalamus and anterior pituitary gland
Karsch, F. J. (1984) · Cambridge University Press eBooks · doi:10.1017/cbo9781139167727.004 · Cited by 48 · cited 1× · see citing works
“The pulsatile release of gonadotropin-releasing hormone (GnRH) is a prerequisite for sustaining normal gonadotropin secretion in mammals (Knobil, 1980; Karsch, 1984); however, the cellular and molecular mechanisms that generate the rhythmic discharge of GnRH are unknown.”
BackgroundJung, M., Michaud, J. C., Steinberg, R., Barnouin, M. C., Hayar, A. M., Mons, G., Souilhac, J., Emonds‐Alt, X., Soubrié, P., & Fur, G. L. (1996) · Neuroscience · doi:10.1016/0306-4522(96)00150-9 · Cited by 44 · cited 1× · see citing works
“For example, activation of NK3 increases firing in noradrenergic and dopaminergic neurons (Jung et al., 1996; Nalivaiko et al., 1997), whereas NK3 antagonists attenuate pharmacologically induced firing of dopaminergic neurons (Gueudet et al., 1999).”
BackgroundVaillend, C., Ungerer, A., & Billard, J. (1999) · Synapse · doi:10.1002/(sici)1098-2396(199907)33:1 · Cited by 40 · see citing works
Gallo, R. V. (1990) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.1990.tb00465.x · Cited by 39 · cited 1× · see citing works
“Since Dyn inhibits MUA volleys and central administration of nor-BNI reverses the inhibitory effect of P on pulsatile LH secretion (Gallo, 1990; Goodman et al., 2004), Dyn/KOR signaling could also mediate the negativefeedback action of P.”
BackgroundIchimaru, T., Mori, Y., & Okamura, H. (2001) · Endocrinology · doi:10.1210/endo.142.6.8002 · Cited by 38 · cited 2× · see citing works
“MUA was recorded as previously described (Mori et al., 1991; Ichimaru et al., 2001; Ohkura et al., 2009) with a slight modification.”
BackgroundMethodWakabayashi, Y., Ohkura, S., Okamura, H., Mori, Y., & Ichikawa, M. (2007) · The Journal of Comparative Neurology · doi:10.1002/cne.21394 · Cited by 26 · cited 1× · see citing works
“Double labeling of mRNA and proteins on the same section was performed as previously described (Wakabayashi et al., 2007; Ohkura et al., 2009).”
MethodIchimaru, T. (2001) · Endocrinology · doi:10.1210/en.142.6.2489 · Cited by 23 · see citing works
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Dynamics of gonadotropin-releasing hormone release during a pulse.
Moenter, S. M., Brand, R. M., MIDGLEY, A. R., & Karsch, F. J. (1992) · Endocrinology · doi:10.1210/endo.130.1.1727719 · Cited by 1,257 · see citing works
Neuropeptide Transmission in Brain Circuits
van den Pol, A. N. (2012) · Neuron · doi:10.1016/j.neuron.2012.09.014 · Cited by 810 · see citing works
“Dynorphin and neurokinin B colocalize with kisspeptin in many mammals (Goodman et al, 2007); dynorphin is proposed to act back on the releasing kisspeptin neurons to synchronize and shape pulsatile release patterns of kisspeptin (Navarro et al, 2009; Wakabayashi et al, 2010).”
BackgroundKisspeptins and Reproduction: Physiological Roles and Regulatory Mechanisms
Pinilla, L., Aguilar, E., Diéguez, C., Millar, R. P., & Tena‐Sempere, M. (2012) · Physiological Reviews · doi:10.1152/physrev.00037.2010 · Cited by 802 · see citing works
“Thereafter, the presence of such KNDy neurons has been documented by a combination of in situ hybridization and IHC techniques in the mouse, goat, and monkey, although in the latter only NKB coexpression was analyzed (304, 305, 363, 491).”
BackgroundMethodInfluentialLehman, M. N., Coolen, L. M., & Goodman, R. L. (2010) · Endocrinology · doi:10.1210/en.2010-0022 · Cited by 768 · see citing works
“Although each of these three peptides is found in separate sets of neurons in other brain regions, recent evidence suggests that the colocalization of KNDy peptides seen in the ARC is unique among brain regions and is conserved across multiple mammalian species that include the rat (17), mouse (18), sheep (13), and go…”
BackgroundWitchel, S. F., Oberfield, S. E., & Peña, A. S. (2019) · Journal of the Endocrine Society · doi:10.1210/js.2019-00078 · Cited by 653 · see citing works
“Although GnRH and LH pulses generally exhibit a 1:1 ratio, preclinical data exist suggesting that a faster GnRH pulse frequency may be associated with decreased LH secretion [52].”
BackgroundDefinition of the hypothalamic GnRH pulse generator in mice
Clarkson, J., Han, S. Y., Piet, R., McLennan, T., Kane, G. M., Ng, J., Porteous, R. W., Kim, J. S., Colledge, W. H., Iremonger, K. J., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1713897114 · Cited by 392 · see citing works
“Alongside anatomical evidence, it has been suggested that the ARN neurons may exhibit synchronized behavior that could intermittently activate GnRH neurons and, thus, act as a pulse generator (15, 16, 19).”
BackgroundRance, N. E., Dacks, P. A., Mittelman-Smith, M. A., Romanovsky, A. A., & Krajewski-Hall, S. J. (2013) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2013.07.003 · Cited by 380 · see citing works
“Coexpression of kisspeptin, NKB and dynorphin (the KNDy peptides) have been identified in the arcuate nucleus of the mouse, rat, goat, monkey and sheep (Burke et al., 2006; Goodman et al., 2007; Navarro et al., 2009; Ramaswamy et al., 2010; Rance and Bruce, 1994; Rometo et al., 2007; Smith, 2009; Smith et al., 2005a;…”
BackgroundInfluentialEpigenetic control of female puberty
Lomniczi, A., Loche, A., Castellano, J. M., Rønnekleiv, O. K., Bosch, M. A., Kaidar, G., Knoll, J. G., Wright, H., Pfeifer, G. P., & Ojeda, S. R. (2013) · Nature Neuroscience · doi:10.1038/nn.3319 · Cited by 307 · see citing works
60 YEARS OF NEUROENDOCRINOLOGY: The hypothalamo-pituitary–gonadal axis
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The Gonadotropin-Releasing Hormone Pulse Generator
Herbison, A. E. (2018) · Endocrinology · doi:10.1210/en.2018-00653 · Cited by 261 · see citing works
Treatment and Outcomes of Precocious Puberty: An Update
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“org J Clin Endocrinol Metab, June 2013, 98(6):2198–2207 doi: 10.”
BackgroundInfluentialSmith, J. T., Li, Q., Yap, K. S., Shahab, M., Roseweir, A. K., Millar, R. P., & Clarke, I. J. (2011) · Endocrinology · doi:10.1210/en.2010-1225 · Cited by 254 · see citing works
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“vicinity of KNDy neurons in the ARC of the goat (15).”
BackgroundSelf-citationPhysiology of the Adult Gonadotropin-Releasing Hormone Neuronal Network
Herbison, A. E. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-397175-3.00011-9 · Cited by 255 · see citing works
Interactions between kisspeptin and neurokinin B in the control of GnRH secretion in the female rat
Navarro, V. M., Castellano, J. M., McConkey, S. M., Pineda, R., Ruíz-Pino, F., Pinilla, L., Clifton, D. K., Tena‐Sempere, M., & Steiner, R. A. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00517.2010 · Cited by 251 · see citing works
Goodman, R. L., Hileman, S. M., Nestor, C. C., Porter, K. L., Connors, J. M., Hardy, S. L., Millar, R. P., Cernea, M., Coolen, L. M., & Lehman, M. N. (2013) · Endocrinology · doi:10.1210/en.2013-1331 · Cited by 234 · see citing works
“They are thus called kisspeptin/neurokinin B/dynorphin (KNDy) neurons (8) and are found in sheep (12), rats (13, 14), mice (10), and goats (9).”
BackgroundResultInfluentialServili, A., Page, Y. L., Leprince, J., Caraty, A., Escobar, S., Parhar, I. S., Seong, J. Y., Vaudry, H., & Kah, O. (2011) · Endocrinology · doi:10.1210/en.2010-0948 · Cited by 223 · see citing works
“In mammals, KISS1 is expressed in both the preoptic area and the ventral hypothalamus (9, 14, 39, 40), and there is no KISS2 gene (16, 17).”
BackgroundNeuroendocrine control of the onset of puberty
Plant, T. M. (2015) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2015.04.002 · Cited by 213 · see citing works
“A critical evaluation of this model is beyond the scope of this review but the evidence upon which the KNDy model of pulse generation is based has been recently documented in several excellent papers (Lehman et al., 2010; Rance et al., 2010; Wakabayashi et al., 2010; Goodman et al., 2014).”
Mittelman‐Smith, M. A., Williams, H., Krajewski, S. J., McMullen, N. T., & Rance, N. E. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1211517109 · Cited by 208 · see citing works
Qiu, J., Nestor, C. C., Zhang, C., Padilla, S. L., Palmiter, R. D., Kelly, M. J., & Rønnekleiv, O. K. (2016) · eLife · doi:10.7554/elife.16246 · Cited by 199 · see citing works
“…3 (Tacr3) and Dyn/k-opioid receptor (KOR) signaling have been proposed to play a critical role in the generation of episodic GnRH/LH pulses via direct and synchronized action on GnRH nerve terminals in the median eminence (Navarro et al., 2009; Ohkura et al., 2009; Wakabayashi et al., 2010).”
BackgroundNeurokinin B and the hypothalamic regulation of reproduction
Rance, N. E., Krajewski, S. J., Smith, M. A., Cholanian, M., & Dacks, P. A. (2010) · Brain Research · doi:10.1016/j.brainres.2010.08.059 · Cited by 203 · see citing works
“First demonstrated in the ewe (Goodman et al., 2007), kisspeptin (or its mRNA) is coexpressed with NKB in the arcuate nucleus in the rat (Kirigiti et al., 2009), mouse (Navarro et al., 2009) and goat (Wakabayashi et al., 2010).”
BackgroundMethodInfluentialMittelman‐Smith, M. A., Williams, H., Krajewski, S. J., Lai, J. Y., Ciofi, P., McMullen, N. T., & Rance, N. E. (2012) · Endocrinology · doi:10.1210/en.2012-1045 · Cited by 189 · see citing works
Neurobiological mechanisms underlying GnRH pulse generation by the hypothalamus
Maeda, K., Ohkura, S., Uenoyama, Y., Wakabayashi, Y., Oka, Y., Tsukamura, H., & Okamura, H. (2010) · Brain Research · doi:10.1016/j.brainres.2010.10.026 · Cited by 192 · see citing works
Kallmann syndrome: phenotype and genotype of hypogonadotropic hypogonadism
Stamou, M. I., & Georgopoulos, N. A. (2017) · Metabolism · doi:10.1016/j.metabol.2017.10.012 · Cited by 194 · see citing works
Moore, A. M., Coolen, L. M., Porter, D. T., Goodman, R. L., & Lehman, M. N. (2018) · Endocrinology · doi:10.1210/en.2018-00389 · Cited by 190 · see citing works
Han, S. Y., McLennan, T., Czieselsky, K., & Herbison, A. E. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1512243112 · Cited by 189 · see citing works
“Although the identity of the neural elements giving rise to multiunit activity are unknown, it has been suggested that they may represent the activity of kisspeptin neurons within the ARN (19).”
BackgroundKisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men
George, J. T., Veldhuis, J. D., Roseweir, A. K., Newton, C. L., Faccenda, E., Millar, R. P., & Anderson, R. A. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-0089 · Cited by 186 · see citing works
“However, it is possible that endogenous release of kisspeptin is pulsatile, and pulsatile administration may have a different impact on GnRH pulsatility, modulated by cotransmitters such as neurokinins and dynorphins (39).”
BackgroundRole of Neurokinin B in the Control of Female Puberty and Its Modulation by Metabolic Status
Navarro, V. M., Ruíz-Pino, F., Sanchez-Garrido, M. A., García-Galiano, D., Hobbs, S. J., Manfredi-Lozano, M., León, S., Sangiao‐Alvarellos, S., Castellano, J. M., Clifton, D. K., et al. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.4288-11.2012 · Cited by 183 · see citing works
“…function that appears to be mediated, at least partially, by its ability to autoregulate the activity of Kiss1 neurons in the ARC (Lehman et al., 2010; Wakabayashi et al., 2010; Navarro et al., 2011a) and is dependent on preserved kisspeptin signaling (Ramaswamy et al., 2011; García-Galiano et…”
BackgroundEndocrinology of the aging male
de Araújo, A. B., & Wittert, G. (2011) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2010.11.004 · Cited by 180 · see citing works
Neuroanatomy of the kisspeptin signaling system in mammals: comparative and developmental aspects
Lehman, M. N., Hileman, S. M., & Goodman, R. L. (2013) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4614-6199-9_3 · Cited by 180 · see citing works
“G oa t + + + + [ 3 6 – 38 ]”
BackgroundInfluentialYip, S. H., Boehm, U., Herbison, A. E., & Campbell, R. E. (2015) · Endocrinology · doi:10.1210/en.2015-1131 · Cited by 178 · see citing works
Neuroendocrine control by kisspeptins: role in metabolic regulation of fertility
Navarro, V. M., & Tena‐Sempere, M. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.147 · Cited by 177 · see citing works
“Thus, colocalization of mRNA encoding dynorphin A and neurokinin B has been demonstrated in the arcuate nucleus of goats and mice (encoded by Pdyn and Tac2 , respectively, in these species) by in situ hybridization”
BackgroundCangiano, B., Swee, D. S., Quinton, R., & Bonomi, M. (2020) · Human Genetics · doi:10.1007/s00439-020-02147-1 · Cited by 182 · see citing works
Comprehensive Review on Kisspeptin and Its Role in Reproductive Disorders
Clarke, H., Dhillo, W. S., & Jayasena, C. N. (2015) · Endocrinology and Metabolism · doi:10.3803/enm.2015.30.2.124 · Cited by 175 · see citing works
Anatomy of the kisspeptin neural network in mammals
Lehman, M. N., Merkley, C. M., Coolen, L. M., & Goodman, R. L. (2010) · Brain Research · doi:10.1016/j.brainres.2010.09.020 · Cited by 172 · see citing works
“, 2009), and the temporal association of these electrophysiological rhythms with GnRH/LH pulses has led to speculation that they comprise a critical component of the “GnRH pulse generator” (Lehman et al., 2010; Navarro et al., 2009; Wakabayashi et al., 2010).”
BackgroundInfluentialYeo, S., & Herbison, A. E. (2011) · Endocrinology · doi:10.1210/en.2011-0164 · Cited by 174 · see citing works
García-Galiano, D., Schenau, D. V. I., León, S., Krajnc-Franken, M. A. M., Manfredi-Lozano, M., Romero‐Ruíz, A., Navarro, V. M., Gaytán, F., van Noort, P. I., Pinilla, L., et al. (2011) · Endocrinology · doi:10.1210/en.2011-1260 · Cited by 165 · see citing works
Neuroendocrine control of gonadotropin‐releasing hormone: Pulsatile and surge modes of secretion
Goodman, R. L., Herbison, A. E., Lehman, M. N., & Navarro, V. M. (2022) · Journal of Neuroendocrinology · doi:10.1111/jne.13094 · Cited by 157 · see citing works
Self-citationThe role of kisspeptin neurons in reproduction and metabolism
Harter, C. J. L., Kavanagh, G. S., & Smith, J. T. (2018) · Journal of Endocrinology · doi:10.1530/joe-18-0108 · Cited by 164 · see citing works
Young, J., George, J. T., Tello, J. A., Francou, B., Bouligand, J., Guiochon‐Mantel, A., Brailly‐Tabard, S., Anderson, R. A., & Millar, R. P. (2012) · Neuroendocrinology · doi:10.1159/000336376 · Cited by 158 · see citing works
True, C. A., Kirigiti, M. A., Ciofi, P., Grove, K. L., & Smith, M. S. (2010) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2010.02076.x · Cited by 159 · see citing works
Hypothalamo-Pituitary axis and puberty
Spaziani, M., Tarantino, C., Tahani, N., Gianfrilli, D., Sbardella, E., Lenzi, A., & Radicioni, A. F. (2020) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2020.111094 · Cited by 165 · see citing works
Sex Steroids and the Control of the Kiss1 System: Developmental Roles and Major Regulatory Actions
García-Galiano, D., Pinilla, L., & Tena‐Sempere, M. (2011) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2011.02230.x · Cited by 153 · see citing works
Ruka, K. A., Burger, L. L., & Moenter, S. M. (2013) · Endocrinology · doi:10.1210/en.2013-1268 · Cited by 150 · see citing works
“Senktide increased the frequency of MUA peaks in multiple steroid milieus (48).”
BackgroundTakahashi, A., Kanda, S., Abe, T., & Oka, Y. (2016) · Endocrinology · doi:10.1210/en.2016-1356 · Cited by 148 · see citing works
Molecular Properties of Kiss1 Neurons in the Arcuate Nucleus of the Mouse
Gottsch, M. L., Popa, S. M., Lawhorn, J. K., Qiu, J., Tonsfeldt, K. J., Bosch, M. A., Kelly, M. J., Rønnekleiv, O. K., Sanz, E., McKnight, G. S., et al. (2011) · Endocrinology · doi:10.1210/en.2011-1521 · Cited by 141 · see citing works
Kisspeptins in Reproductive Biology: Consensus Knowledge and Recent Developments1
Roa, J., Navarro, V. M., & Tena‐Sempere, M. (2011) · Biology of Reproduction · doi:10.1095/biolreprod.111.091538 · Cited by 142 · see citing works
“This neuronal population has been proposed as a central node for the integral control of GnRH secretion, not only by virtue of its ability to activate GnRH neurons via direct Kp stimulation, but also because of the capacity of NKB and Dyn to reciprocally and finely regulate such Kp output [55, 68].”
BackgroundResultInfluentialNagae, M., Uenoyama, Y., Okamoto, S., Tsuchida, H., Ikegami, K., Goto, T., Majarune, S., Nakamura, S., Sanbo, M., Hirabayashi, M., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2009156118 · Cited by 141 · see citing works
“Specifically, ARC kisspeptin neurons are also referred to as KNDy neurons because the ARC kisspeptin neurons express neurokinin B (NKB, encoded by the Tac3 gene) and dynorphin A (Dyn, encoded by the Pdyn gene) (22, 27, 28).”
BackgroundMolecular regulation of hypothalamus–pituitary–gonads axis in males
Jin, J., & Yang, W. (2014) · Gene · doi:10.1016/j.gene.2014.08.048 · Cited by 135 · see citing works
Epigenetic regulation of female puberty
Lomniczi, A., Wright, H., & Ojeda, S. R. (2015) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.08.003 · Cited by 136 · see citing works
Ramaswamy, S., Seminara, S. B., & Plant, T. M. (2011) · Neuroendocrinology · doi:10.1159/000329045 · Cited by 132 · see citing works
GnRH Pulse Generator Activity Across the Estrous Cycle of Female Mice
McQuillan, H. J., Han, S. Y., Cheong, I., & Herbison, A. E. (2019) · Endocrinology · doi:10.1210/en.2019-00193 · Cited by 127 · see citing works
“share many similarities with past ARN multiunit activity (MUA) recordings making it likely that MUA represents the electrical activity of ARN neurons (3, 8).”
BackgroundThe integrated hypothalamic tachykinin-kisspeptin system as a central coordinator for reproduction
Navarro, V. M., Bosch, M. A., León, S., Simavli, S., True, C., Pinilla, L., Carroll, R. S., Seminara, S. B., Tena-Sempere, M., Rønnekleiv, O. K., et al. (2015) · Endocrinology · doi:10.1210/en.2014-1651 · Cited by 128 · see citing works
Uenoyama, Y., Nakamura, S., Hayakawa, Y., Ikegami, K., Watanabe, Y., Deura, C., Minabe, S., Tomikawa, J., Goto, T., Ieda, N., et al. (2015) · Journal of Neuroendocrinology · doi:10.1111/jne.12257 · Cited by 127 · see citing works
Hanchate, N. K., Parkash, J., Bellefontaine, N., Mazur, D., Colledge, W. H., de Tassigny, X. D., & Prévot, V. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.4765-11.2012 · Cited by 125 · see citing works
“…Hrabovszky et al., 2010) and that have been postulated to drive short feedback loops within the tuberal region of the hypothalamus to control the rhythmic discharge of kisspeptin and induce the release of GnRH from fibers in the median eminence (Navarro et al., 2009; Wakabayashi et al., 2010).”
BackgroundVazquez, M. J., Toro, C. A., Castellano, J. M., Ruíz-Pino, F., Roa, J., Beiroa, D., Heras, V., Velasco, I., Diéguez, C., Pinilla, L., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06459-9 · Cited by 129 · see citing works
Hrabovszky, E., Sipos, M. T., Molnár, C. S., Ciofi, P., Borsay, B. Á., Gergely, P., Herczeg, L., Bloom, S. R., Ghatei, M. A., Dhillo, W. S., et al. (2012) · Endocrinology · doi:10.1210/en.2012-1545 · Cited by 124 · see citing works
“Senktide also stimulated LH secretion in castrated male monkeys (16), and in the 340 follicular, but not in the luteal, phase in ewes (38), whereas reduced net LH secretion was observed in 341 ovariectomized goats (8).”
BackgroundMethodResultInfluentialNew Insights into the Control of Pulsatile GnRH Release: The Role of Kiss1/Neurokinin B Neurons
Navarro, V. M. (2012) · Frontiers in Endocrinology · doi:10.3389/fendo.2012.00048 · Cited by 120 · see citing works
“…of NKB to goats induces a clear increase in the frequency and amplitude of MUA volleys in the ARC, which were invariably mirrored by LH pulses (Wakabayashi et al., 2010; Figure 3), yet the administration of kisspeptin modified LH pulses without modifying MUA volleys (Ohkura et al., 2009); (e)…”
BackgroundInfluentialEvidence of a Role for Kisspeptin and Neurokinin B in Puberty of Female Sheep
Nestor, C. C., Briscoe, A. M. S., Davis, S. M., Valent, M., Goodman, R. L., & Hileman, S. M. (2012) · Endocrinology · doi:10.1210/en.2011-2009 · Cited by 118 · see citing works
Osuka, S., Nakanishi, N., Murase, T., Nakamura, T., Goto, M., Iwase, A., & Kikkawa, F. (2018) · Reproductive Medicine and Biology · doi:10.1002/rmb2.12262 · Cited by 125 · see citing works
Nestor, C. C., Qiu, J., Padilla, S. L., Zhang, C., Bosch, M. A., Fan, W., Aicher, S. A., Palmiter, R. D., Rønnekleiv, O. K., & Kelly, M. J. (2016) · Molecular Endocrinology · doi:10.1210/me.2016-1026 · Cited by 118 · see citing works
The inhibitory effects of neurokinin B on GnRH pulse generator frequency in the female rat
Kinsey-Jones, J. S., Grachev, P., Li, X. F., Lin, Y. S., Milligan, S. R., Lightman, S. L., & O'Byrne, K. T. (2012) · Endocrinology · doi:10.1210/en.2011-1641 · Cited by 114 · see citing works
“It is postulated that the NKB/NK3R, kisspeptin/GPR54, and Dyn/ KOR signaling systems form a hierarchical mode of action within ARC neural networks and that NKB may act upstream of kisspeptin and Dyn to regulate pulsatile LH secretion.”
BackgroundResultInfluentialde Croft, S., Piet, R., Mayer, C., Mai, O., Boehm, U., & Herbison, A. E. (2012) · Endocrinology · doi:10.1210/en.2012-1616 · Cited by 101 · see citing works
Uenoyama, Y., Nagae, M., Tsuchida, H., Inoue, N., & Tsukamura, H. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.724632 · Cited by 112 · see citing works
Current and future applications of GnRH, kisspeptin and neurokinin B analogues
Millar, R. P., & Newton, C. L. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.120 · Cited by 106 · see citing works
Uenoyama, Y., Inoue, N., Pheng, V., Homma, T., Takase, K., Yamada, S., Ajiki, K., Ichikawa, M., Okamura, H., Maeda, K., et al. (2011) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2011.02199.x · Cited by 106 · see citing works
Qiu, J., Rivera, H. M., Bosch, M. A., Padilla, S. L., Stincic, T. L., Palmiter, R. D., Kelly, M. J., & Rønnekleiv, O. K. (2018) · eLife · doi:10.7554/elife.35656 · Cited by 114 · see citing works
Francou, B., Bouligand, J., Voican, A., Amazit, L., Trabado, S., Fagart, J., Méduri, G., Brailly‐Tabard, S., Chanson, P., Lecomte, P., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025614 · Cited by 103 · see citing works
Epigenetic regulation of puberty via Zinc finger protein-mediated transcriptional repression
Lomniczi, A., Wright, H., Castellano, J. M., Matagne, V., Toro, C. A., Ramaswamy, S., Plant, T. M., & Ojeda, S. R. (2015) · Nature Communications · doi:10.1038/ncomms10195 · Cited by 102 · see citing works
Kisspeptin and Puberty in Mammals
Terasawa, E., Guerriero, K. A., & Plant, T. M. (2013) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-6199-9_12 · Cited by 103 · see citing works
Chan, Y.-M., Butler, J. P., Sidhoum, V. F., Pinnell, N. E., & Seminara, S. B. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-1282 · Cited by 100 · see citing works
Human GnRH Deficiency: A Unique Disease Model to Unravel the Ontogeny of GnRH Neurons
Balasubramanian, R., Dwyer, A. A., Seminara, S. B., Pitteloud, N., Kaiser, U. B., & Crowley, W. F. (2010) · Neuroendocrinology · doi:10.1159/000314193 · Cited by 99 · see citing works
Kisspeptin and GnRH Pulse Generation
Okamura, H., Tsukamura, H., Ohkura, S., Uenoyama, Y., Wakabayashi, Y., & Maeda, K. (2013) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-6199-9_14 · Cited by 101 · see citing works
Kisspeptin neurons from mice to men: similarities and differences
Goodman, R. L., & Lehman, M. N. (2012) · Endocrinology · doi:10.1210/en.2012-1550 · Cited by 103 · see citing works
κ-Opioid Receptor Is Colocalized in GnRH and KNDy Cells in the Female Ovine and Rat Brain
Weems, P. W., Witty, C. F., Amstalden, M., Coolen, L. M., Goodman, R. L., & Lehman, M. N. (2016) · Endocrinology · doi:10.1210/en.2015-1763 · Cited by 95 · see citing works
Mechanism of kisspeptin neuron synchronization for pulsatile hormone secretion in male mice
Han, S. Y., Morris, P. G., Kim, J.-C., Guru, S., Pardo-Navarro, M., Yeo, S.-H., McQuillan, H. J., & Herbison, A. E. (2023) · Cell Reports · doi:10.1016/j.celrep.2022.111914 · Cited by 91 · see citing works
“41 Whereas glutamate will be released from ARN KISS neurons terminals at very low firing frequencies, NKB transmission only occurs when the neuron reaches 10–20 Hz activation.”
Co‐Localisation of Kisspeptin with Galanin or Neurokinin B in Afferents to Mouse GnRH Neurones
Kalló, I., Vida, B., Deli, L., Molnár, C. S., Hrabovszky, E., Caraty, A., Ciofi, P., Coen, C. W., & Liposits, Z. (2011) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2011.02262.x · Cited by 94 · see citing works
Kanda, S. (2018) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2018.11.014 · Cited by 95 · see citing works
“Interestingly, GnRH analogues alone could induce ovulation in Siberian sturgeon (Williot et al., 2002), which is a non-teleost actinopterygian species.”
BackgroundPhysiology of Gnrh and Gonadotropin Secretion
Marques, P., Skorupskaite, K., George, J. T., & Anderson, R. A. (2015) · Cited by 95 · see citing works
True, C. A., Kirigiti, M. A., Kievit, P., Grove, K. L., & Smith, M. S. (2011) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2011.02144.x · Cited by 93 · see citing works
Plant, T. M. (2012) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2012.02.002 · Cited by 93 · see citing works
Grachev, P., Li, X. F., Kinsey‐Jones, J. S., di Domenico, A., Millar, R. P., Lightman, S. L., & O'Byrne, K. T. (2012) · Endocrinology · doi:10.1210/en.2012-1574 · Cited by 92 · see citing works
“There is a substantial body of morphological evidence that confirms a high degree of coexpression between NKB and Dyn within ARC KNDy neurons in a variety of mammalian species, including mouse (6), rat (4), ewe (3), and goat (7), as well as in humans and nonhuman primates (39).”
BackgroundInfluentialGill, J. C., Navarro, V. M., Kwong, C., Noel, S. D., Martin, C., Xu, S., Clifton, D. K., Carroll, R. S., Steiner, R. A., & Kaiser, U. B. (2012) · Endocrinology · doi:10.1210/en.2012-1529 · Cited by 90 · see citing works
Sex Steroid Regulation of Kisspeptin Circuits
Smith, J. T. (2013) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-6199-9_13 · Cited by 90 · see citing works
Central Mechanism Controlling Pubertal Onset in Mammals: A Triggering Role of Kisspeptin
Uenoyama, Y., Inoue, N., Nakamura, S., & Tsukamura, H. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00312 · Cited by 89 · see citing works
“They also demonstrated that the frequency of the rhythmic increases in the MUA was suppressed by a central administration of dynorphin A and facilitated by antagonism of the kappa-opioid receptor (KOR, which preferably binds to dynorphin A) signaling in goats (89).”
BackgroundNeuroanatomy of the Human Hypothalamic Kisspeptin System
Hrabovszky, E. (2013) · Neuroendocrinology · doi:10.1159/000356903 · Cited by 88 · see citing works
Stamou, M. I., Cox, K. H., & Crowley, W. F. (2015) · Endocrine Reviews · doi:10.1210/er.2015-1045 · Cited by 91 · see citing works
RetractedHypothalamus as an Endocrine Organ
Clarke, I. J. (2014) · Comprehensive physiology · doi:10.1002/cphy.c140019 · Cited by 104 · see citing works
Kisspeptin neurons mediate reflex ovulation in the musk shrew ( Suncus murinus )
Inoue, N., Sasagawa, K., Ikai, K., Sasaki, Y., Tomikawa, J., Oishi, S., Fujii, N., Uenoyama, Y., Ohmori, Y., Yamamoto, N., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113035108 · Cited by 85 · see citing works
“Kisspeptin neurons play a role in the generation of the surge mode of GnRH/LH release to mediate the estrogenpositive feedback effect and then ovulation (18–21) as well as the pulsatile GnRH/LH release responsible for follicular maturation (22, 23).”
BackgroundMOSTARI, M. P., Ieda, N., Deura, C., Minabe, S., Yamada, S., Uenoyama, Y., Maeda, K., & Tsukamura, H. (2013) · Journal of Reproduction and Development · doi:10.1262/jrd.2012-193 · Cited by 81 · see citing works
“The ARC kisspeptin neurons are recently referred to as KNDy neurons [19] because they co-express neurokinin B (NKB) and dynorphin (Dyn) [15, 17, 21].”
BackgroundInfluentialWakabayashi, Y., Yamamura, T., Sakamoto, K., Mori, Y., & OKAMURA, H. (2012) · Journal of Reproduction and Development · doi:10.1262/jrd.2012-136 · Cited by 84 · see citing works
“In a variety of species such as mice [16], rats [17], goats [18], sheep [19] and monkeys [20], kisspeptin neurons in the ARC have been shown to concomitantly express other neuropeptides implicated in the control of reproduction, including neurokinin B (NKB) and dynorphin A (Dyn) [21–23].”
BackgroundMethodInfluentialLi, X. F., Lin, Y. S., Kinsey‐Jones, J. S., & O'Byrne, K. T. (2012) · Endocrinology · doi:10.1210/en.2012-1223 · Cited by 83 · see citing works
Toro, C. A., Wright, H., Aylwin, C. F., Ojeda, S. R., & Lomniczi, A. (2017) · Nature Communications · doi:10.1038/s41467-017-02512-1 · Cited by 81 · see citing works
Uenoyama, Y., Inoue, N., Nakamura, S., & Tsukamura, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179229 · Cited by 82 · see citing works
“The frequency of KNDy neuronal activity recorded by the MUA volley was increased and decreased by a central administration of NKB and Dyn, respectively, in goats [87,104].”
BackgroundHu, M., Li, X. F., McCausland, B., Li, S. Y., Gresham, R., Kinsey‐Jones, J. S., Gardiner, J., Sam, A. H., Bloom, S. R., Poston, L., et al. (2015) · Endocrinology · doi:10.1210/en.2014-1655 · Cited by 78 · see citing works
“Our data fit well with the developing rodent KNDyGnRH dendron mode, which has shown that pulsed ARC KNDy neuron kisspeptin acting through Kiss1r on GnRH dendrons is crucial for GnRH pulse generation, although it is probably not the pulse generator per se (19, 73) because the electrical recording of ARC kisspeptin/KNDy…”
BackgroundResultHrabovszky, E. (2011) · Frontiers in Endocrinology · doi:10.3389/fendo.2011.00080 · Cited by 80 · see citing works
Fraser, G. L., Hoveyda, H. R., Clarke, I. J., Ramaswamy, S., Plant, T. M., Rose, C., & Millar, R. P. (2015) · Endocrinology · doi:10.1210/en.2015-1409 · Cited by 79 · see citing works
Quillet, R., Ayachi, S., Bihel, F. J. ‐., Elhabazi, K., Ilien, B., & Simonin, F. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.02.005 · Cited by 80 · see citing works
Neuropeptide co-expression in hypothalamic kisspeptin neurons of laboratory animals and the human
Skrapits, K., Borsay, B. Á., Herczeg, L., Ciofi, P., Liposits, Z., & Hrabovszky, E. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00029 · Cited by 77 · see citing works
“…the reported colocalization patterns vary largely by species, sex and age (Burke et al., 2006; Goodman et al., 2007; Navarro et al., 2009, 2011a; Amstalden et al., 2010; Cheng et al., 2010; Ramaswamy et al., 2010; Wakabayashi et al., 2010; Hrabovszky et al., 2011, 2012; Overgaard et al., 2014).”
Background
- Authors
- Wakabayashi, Y., Nakada, T., Murata, K., Ohkura, S., Mogi, K., Navarro, V. M., Clifton, D. K., Mori, Y., Tsukamura, H., Maeda, K.-I., Steiner, R. A., & Okamura, H.
- Affiliations
- Institute of Agrobiological Sciences (JP)
- Nagoya University (JP)
- University of Washington (US)
- The University of Tokyo (JP)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-02-24
- Volume
- 30
- Issue
- 8
- Pages
- 3124-3132
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6633939
- OpenAlex
- W2045555035
- Cited by
- 597
- References
- 42
- Citations by year
- 2026: 12 · 2025: 27 · 2024: 19 · 2023: 24 · 2022: 32 · 2021: 36 · 2020: 38 · 2019: 36 · 2018: 42 · 2017: 39 · 2016: 42 · 2015: 42 · 2014: 54 · 2013: 48 · 2012: 47
- FWCI
- 58.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5u54hd012629-31)
- National Institute of Child Health and Human Development
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD049651, U54-HD-12629, U54HD-012629)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- kisspeptin neurons, arcuate nucleus, neurokinin B, dynorphin A, pulsatile GnRH secretion, luteinizing hormone, multi-unit activity, goats, neuroendocrine regulation of reproduction
- MeSH terms
- Action Potentials, Animals, Arcuate Nucleus of Hypothalamus, Biological Clocks, Dynorphins, Electrophysiology, Female, Goats, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Neurons, Neurosecretory Systems, Ovariectomy, Periodicity, Proteins, Reproduction, Gonadal Steroid Hormones, Neurokinin B, Tumor Suppressor Proteins, Estrous Cycle, Kisspeptins
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