Low degree of overlap between kisspeptin, neurokinin B, and dynorphin immunoreactivities in the infundibular nucleus of young male human subjects challenges the KNDy neuron concept

Hrabovszky, Erik; Sipos, Máté T.; Molnár, Csilla S.; Ciofi, Philippe; Borsay, Beáta Á.; Gergely, Péter; Herczeg, László; Bloom, Stephen R.; Ghatei, Mohammad A.; Dhillo, Waljit S.; Liposits, Zsolt

doi:10.1210/en.2012-1545

Cited by 124Hypothalamic control of reproductive hormonesNeuropeptides and Animal PhysiologyNeuroendocrine regulation and behavior

Low degree of overlap between kisspeptin, neurokinin B, and dynorphin immunoreactivities in the infundibular nucleus of young male human subjects challenges the KNDy neuron concept

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Hrabovszky, Erik, Sipos, Máté T., Molnár, Csilla S., Ciofi, Philippe, Borsay, Beáta Á., Gergely, Péter, Herczeg, László, Bloom, Stephen R. +3 more·2012·Endocrinology

DOI 10.1210/en.2012-1545PMC PMC3512020

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Abstract

Previous immunohistochemical and in situ hybridization studies of sheep, goats, and rodents indicated that kisspeptin (KP), neurokinin B (NKB), and dynorphin A (DYN) are extensively colocalized in the hypothalamic arcuate nucleus, thus providing a basis for the KP/NKB/DYN (KNDy) neuron concept; in both sexes, KNDy neuropeptides have been implicated in the generation of GnRH neurosecretory pulses and in the negative feedback effects of sexual steroids to the reproductive axis. To test the validity and limitations of the KNDy neuron concept in the human, we carried out the comparative immunohistochemical analysis of the three neuropeptides in the infundibular nucleus (Inf; also known as arcuate nucleus) and stalk of young male human individuals (<37 yr). Results of quantitative immunohistochemical experiments established that the regional densities of NKB immunoreactive (IR) perikarya and fibers, and the incidence of afferent contacts they formed onto GnRH neurons, were about 5 times as high as those of the KP-IR elements. Dual-immunofluorescent studies confirmed that considerable subsets of the NKB-IR and KP-IR cell bodies and fibers are separate, and only about 33% of NKB-IR perikarya and 75% of KP-IR perikarya were dual labeled. Furthermore, very few DYN-IR cell bodies could be visualized in the Inf. DYN-IR fibers were also rare and, with few exceptions, distinct from the KP-IR fibers. The abundance and colocalization patterns of the three immunoreactivities showed similar trends in the infundibular stalk around portal blood vessels. Together these results indicate that most NKB neurons in the Inf do not synthesize detectable amounts of KP and DYN in young male human individuals. These data call for a critical use of the KNDy neuron terminology when referring to the putative pulse generator system of the mediobasal hypothalamus. We conclude that the functional importance of these three neuropeptides in reproductive regulation considerably varies among species, between sexes, and at different ages.

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Complete coexpression of kisspeptin, NKB and dynorphin is not always found.
“Complete coexpression of kisspeptin, NKB and dynorphin is not always found (Hrabovszky et al., 2012; Navarro et al., 2011), but this issue is complicated by limitations in the sensitivity of detection (Ruka et al., 2013) and differential expression depending on developmental stage (Gill et al., 2012) or physiological state of the animal (Foradori et al., 2005; Navarro et al., 2011; Rance and Bruce”
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 Hrabovszky et al., 2012

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Tachykinin NK3-receptor deficiency does not inhibit pulmonary eosinophilia in allergic mice
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Tachykinins Induce Secretion of Prolactin from Perifused Rat Anterior Pituitary Cells by Interactions with Two Different Binding Sites
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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
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
Rance, 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
GnRH and GnRH receptors in the pathophysiology of the human female reproductive system
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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
Physiology 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
Kisspeptin, Neurokinin B, and Dynorphin Act in the Arcuate Nucleus to Control Activity of the GnRH Pulse Generator in Ewes
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
Neuroendocrine 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
KNDy Cells Revisited
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
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
Connecting metabolism and gonadal function: Novel central neuropeptide pathways involved in the metabolic control of puberty and fertility
Manfredi-Lozano, M., Roa, J., & Tena-Sempere, M. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2017.07.008 · Cited by 162 · see citing works
Disentangling puberty: novel neuroendocrine pathways and mechanisms for the control of mammalian puberty
Avendaño, M. S., Vazquez, M. J., & Tena‐Sempere, M. (2017) · Human Reproduction Update · doi:10.1093/humupd/dmx025 · Cited by 139 · see citing works
Role of KNDy Neurons Expressing Kisspeptin, Neurokinin B, and Dynorphin A as a GnRH Pulse Generator Controlling Mammalian Reproduction
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
Endogenous opiates and behavior: 2012
Bodnar, R. J. (2013) · Peptides · doi:10.1016/j.peptides.2013.10.001 · Cited by 98 · see citing works
Neuroanatomy of the Human Hypothalamic Kisspeptin System
Hrabovszky, E. (2013) · Neuroendocrinology · doi:10.1159/000356903 · Cited by 88 · see citing works
Hypothalamus as an Endocrine Organ
Clarke, I. J. (2014) · Comprehensive physiology · doi:10.1002/cphy.c140019 · Cited by 104 · see citing works
Kisspeptins and the neuroendocrine control of reproduction: Recent progress and new frontiers in kisspeptin research
Sobrino, V., Avendaño, M. S., Perdices-López, C., Jiménez-Puyer, M., & Tena‐Sempere, M. (2022) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2021.100977 · Cited by 83 · 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
Puberty in Mice and Rats
Prévot, V. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-397175-3.00030-2 · Cited by 78 · see citing works
Evidence for Changes in Numbers of Synaptic Inputs onto KNDy and GnRH Neurones during the Preovulatory LH Surge in the Ewe
Merkley, C. M., Coolen, L. M., Goodman, R. L., & Lehman, M. N. (2015) · Journal of Neuroendocrinology · doi:10.1111/jne.12293 · Cited by 69 · see citing works
A Role for Neurokinin B in Pulsatile GnRH Secretion in the Ewe
Goodman, R. L., Coolen, L. M., & Lehman, M. N. (2013) · Neuroendocrinology · doi:10.1159/000355285 · Cited by 65 · see citing works
Kisspeptin Signaling Is Required for the Luteinizing Hormone Response in Anestrous Ewes following the Introduction of Males
Bond, J. P. D., Li, Q., Millar, R. P., Clarke, I. J., & Smith, J. T. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057972 · Cited by 64 · see citing works
Expression of neurokinin B/NK3 receptor and kisspeptin/KISS1 receptor in human granulosa cells
Garcia-Ortega, J., Pinto, F. M., Sánchez, M. F., Prados, N., Cejudo-Román, A., Almeida, T. A., Hernández, M., Romero, M., Tena‐Sempere, M., & Candenas, L. (2014) · Human Reproduction · doi:10.1093/humrep/deu247 · Cited by 62 · see citing works
Substance P immunoreactivity exhibits frequent colocalization with kisspeptin and neurokinin B in the human infundibular region
Hrabovszky, E., Borsay, B. Á., Rácz, K., Herczeg, L., Ciofi, P., Bloom, S. R., Ghatei, M. A., Dhillo, W. S., & Liposits, Z. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072369 · Cited by 57 · see citing works
Self-citation
KNDy Neurons of the Hypothalamus and Their Role in GnRH Pulse Generation: an Update
Moore, A. M., Novak, A. G., & Lehman, M. N. (2023) · Endocrinology · doi:10.1210/endocr/bqad194 · Cited by 62 · see citing works
Kisspeptin across the human lifespan:evidence from animal studies and beyond
Clarke, S. A., & Dhillo, W. S. (2016) · Journal of Endocrinology · doi:10.1530/joe-15-0538 · Cited by 54 · see citing works
IGF-1 Influences Gonadotropin-Releasing Hormone Regulation of Puberty
Dees, W. L., Hiney, J. K., & Srivastava, V. K. (2021) · Neuroendocrinology · doi:10.1159/000514217 · Cited by 55 · see citing works
The Kiss1 system and polycystic ovary syndrome: lessons from physiology and putative pathophysiologic implications
Witchel, S. F., & Tena‐Sempere, M. (2013) · Fertility and Sterility · doi:10.1016/j.fertnstert.2013.05.024 · Cited by 51 · see citing works
GPCR Heterodimerization in the Reproductive System: Functional Regulation and Implication for Biodiversity
Satake, H., Matsubara, S., Aoyama, M., Kawada, T., & Sakai, T. (2013) · Frontiers in Endocrinology · doi:10.3389/fendo.2013.00100 · Cited by 52 · see citing works
Kisspeptin and Neurokinin B Signaling Network Underlies the Pubertal Increase in GnRH Release in Female Rhesus Monkeys
Garcia, J. P., Guerriero, K. A., Keen, K. L., Kenealy, B. P., Seminara, S. B., & Terasawa, E. (2017) · Endocrinology · doi:10.1210/en.2017-00500 · Cited by 50 · see citing works
The neurobiological mechanism underlying hypothalamic GnRH pulse generation: the role of kisspeptin neurons in the arcuate nucleus
Plant, T. M. (2019) · F1000Research · doi:10.12688/f1000research.18356.2 · Cited by 69 · see citing works
Keeping Puberty on Time
Tena‐Sempere, M. (2013) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/b978-0-12-396968-2.00011-7 · Cited by 46 · see citing works
Morphological Evidence for Enhanced Kisspeptin and Neurokinin B Signaling in the Infundibular Nucleus of the Aging Man
Molnár, C. S., Vida, B., Sipos, M. T., Ciofi, P., Borsay, B. Á., Racz, K., Herczeg, L., Bloom, S. R., Ghatei, M. A., Dhillo, W. S., et al. (2012) · Endocrinology · doi:10.1210/en.2012-1739 · Cited by 46 · see citing works
Clinical Potential of Kisspeptin in Reproductive Health
Abbara, A., Clarke, S. A., & Dhillo, W. S. (2021) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2021.05.008 · Cited by 45 · see citing works
Afferent Neuronal Control of Type-I Gonadotropin Releasing Hormone Neurons in the Human
Hrabovszky, E., & Liposits, Z. (2013) · Frontiers in Endocrinology · doi:10.3389/fendo.2013.00130 · Cited by 43 · see citing works
Hypothalamic Kisspeptin Neurons: Integral Elements of the GnRH System
Prashar, V., Arora, T., Singh, R., Sharma, A., & Parkash, J. (2022) · Reproductive Sciences · doi:10.1007/s43032-022-01027-5 · Cited by 41 · see citing works
Investigating the KNDy Hypothesis in Humans by Coadministration of Kisspeptin, Neurokinin B, and Naltrexone in Men
Narayanaswamy, S., Prague, J., Jayasena, C. N., Papadopoulou, D., Mizamtsidi, M., Shah, A., Bassett, P., Comninos, A. N., Abbara, A., Bloom, S. R., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-1911 · Cited by 39 · see citing works
Hypophysiotropic Gonadotropin-Releasing Hormone Projections Are Exposed to Dense Plexuses of Kisspeptin, Neurokinin B and Substance P Immunoreactive Fibers in the Human: A Study on Tissues from Postmenopausal Women
Borsay, B. Á., Skrapits, K., Herczeg, L., Ciofi, P., Bloom, S. R., Ghatei, M. A., Dhillo, W. S., Liposits, Z., & Hrabovszky, E. (2014) · Neuroendocrinology · doi:10.1159/000368362 · Cited by 39 · see citing works
Disparate Changes in Kisspeptin and Neurokinin B Expression in the Arcuate Nucleus After Sex Steroid Manipulation Reveal Differential Regulation of the Two KNDy Peptides in Rats
Overgaard, A., Ruíz-Pino, F., Castellano, J. M., Tena‐Sempere, M., & Mikkelsen, J. D. (2014) · Endocrinology · doi:10.1210/en.2014-1200 · Cited by 38 · see citing works
Current Perspectives on Kisspeptins Role in Behaviour
Mills, E. G., Yang, L., Abbara, A., Dhillo, W. S., & Comninos, A. N. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.928143 · Cited by 35 · see citing works
KISS1R: Hallmarks of an Effective Regulator of the Neuroendocrine Axis
Millar, R. P., & Babwah, A. V. (2015) · Neuroendocrinology · doi:10.1159/000381457 · Cited by 35 · see citing works
The KiNG of reproduction: Kisspeptin/ nNOS interactions shaping hypothalamic GnRH release
Delli, V., Silva, M. S. B., Prévot, V., & Chachlaki, K. (2021) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2021.111302 · Cited by 34 · see citing works
Estradiol Increases Glutamate and GABA Neurotransmission into GnRH Neurons via Retrograde NO-Signaling in Proestrous Mice during the Positive Estradiol Feedback Period
Farkas, I., Bálint, F., Farkas, E., Vastagh, C., Fekete, C., & Liposits, Z. (2018) · eNeuro · doi:10.1523/eneuro.0057-18.2018 · Cited by 33 · see citing works
Nitric oxide resets kisspeptin-excited GnRH neurons via PIP2 replenishment
Constantin, S., Reynolds, D., Oh, A., Pizano, K., & Wray, S. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2012339118 · Cited by 34 · see citing works
Mechanism of pulsatile GnRH release in primates: Unresolved questions
Terasawa, E. (2019) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2019.110578 · Cited by 32 · see citing works
Does the KNDy Model for the Control of Gonadotropin-Releasing Hormone Pulses Apply to Monkeys and Humans?
Lehman, M. N., He, W., Coolen, L. M., Levine, J. E., & Goodman, R. L. (2019) · Seminars in Reproductive Medicine · doi:10.1055/s-0039-3400254 · Cited by 33 · see citing works
Cellular and molecular mechanisms regulating the KNDy neuronal activities to generate and modulate GnRH pulse in mammals
Ikegami, K., Watanabe, Y., Nakamura, S., Goto, T., Inoue, N., Uenoyama, Y., & Tsukamura, H. (2021) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2021.100968 · Cited by 31 · see citing works
Kisspeptin and neurokinin B: roles in reproductive health
Koysombat, K., Tsoutsouki, J., Patel, A., Comninos, A. N., Dhillo, W. S., & Abbara, A. (2025) · Physiological Reviews · doi:10.1152/physrev.00015.2024 · Cited by 35 · see citing works
The Decline in Pulsatile GnRH Release, as Reflected by Circulating LH Concentrations, During the Infant-Juvenile Transition in the Agonadal Male Rhesus Monkey (Macaca mulatta) Is Associated With a Reduction in Kisspeptin Content of KNDy Neurons of the Arcuate Nucleus in the Hypothalamus
Ramaswamy, S., Dwarki, K., Ali, B. F., Gibbs, R. B., & Plant, T. M. (2013) · Endocrinology · doi:10.1210/en.2012-2154 · Cited by 30 · see citing works
Control of the Menstrual Cycle
Zeleznik, A. J., & Plant, T. M. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-397175-3.00028-4 · Cited by 30 · see citing works
Characterization of Kisspeptin Neurons in the Human Rostral Hypothalamus
Rumpler, É., Skrapits, K., Takács, S., Göcz, B., Trinh, S. H., Rácz, G. A., Matolcsy, A., Kozma, Z., Ciofi, P., Dhillo, W. S., et al. (2020) · Neuroendocrinology · doi:10.1159/000507891 · Cited by 29 · see citing works
Opioidergic pathways and kisspeptin in the regulation of female reproduction in mammals
Uenoyama, Y., Tsuchida, H., Nagae, M., Inoue, N., & Tsukamura, H. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.958377 · Cited by 30 · see citing works
Lateral hypothalamic orexin and melanin-concentrating hormone neurons provide direct input to gonadotropin-releasing hormone neurons in the human
Skrapits, K., Kanti, V., Savanyú, Z., Maurnyi, C., Szenci, O., Horváth, A., Borsay, B. Á., Herczeg, L., Liposits, Z., & Hrabovszky, E. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00348 · Cited by 29 · see citing works
Pubertal orchestration of hormones and testis in primates
Bhattacharya, I., Sharma, S. S., & Majumdar, S. S. (2019) · Molecular Reproduction and Development · doi:10.1002/mrd.23246 · Cited by 28 · see citing works
Emerging Roles of Epigenetics in the Control of Reproductive Function: Focus on Central Neuroendocrine Mechanisms
Vazquez, M. J., Daza‐Dueñas, S., & Tena‐Sempere, M. (2021) · Journal of the Endocrine Society · doi:10.1210/jendso/bvab152 · Cited by 28 · see citing works
Hypothalamus as an Endocrine Organ
Clarke, I. J. (2015) · Comprehensive physiology · doi:10.1002/j.2040-4603.2015.tb00605.x · Cited by 28 · see citing works
Dissecting the KNDy hypothesis: KNDy neuron-derived kisspeptins are dispensable for puberty but essential for preserved female fertility and gonadotropin pulsatility
Velasco, I., Franssen, D., Daza‐Dueñas, S., Skrapits, K., Takács, S., Torres, E., Rodríguez-Vázquez, E., Ruiz-Cruz, M., León, S., Kukoricza, K., et al. (2023) · Metabolism · doi:10.1016/j.metabol.2023.155556 · Cited by 30 · see citing works
Prenatal Testosterone Excess Decreases Neurokinin 3 Receptor Immunoreactivity within the Arcuate Nucleus KND y Cell Population
Ahn, T., Fergani, C., Coolen, L. M., Padmanabhan, V., & Lehman, M. N. (2014) · Journal of Neuroendocrinology · doi:10.1111/jne.12244 · Cited by 27 · see citing works
New Perspectives for Anatomical and Molecular Studies of Kisspeptin Neurons in the Aging Human Brain
Hrabovszky, E., Takács, S., Göcz, B., & Skrapits, K. (2019) · Neuroendocrinology · doi:10.1159/000496566 · Cited by 26 · see citing works
Potential clinical use of kisspeptin
Prague, J. K., & Dhillo, W. S. (2015) · Neuroendocrinology · doi:10.1159/000439133 · Cited by 26 · see citing works
Colocalization of Cocaine- and Amphetamine-Regulated Transcript with Kisspeptin and Neurokinin B in the Human Infundibular Region
Skrapits, K., Borsay, B. Á., Herczeg, L., Ciofi, P., Bloom, S. R., Ghatei, M. A., Dhillo, W. S., Liposits, Z., & Hrabovszky, E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0103977 · Cited by 24 · see citing works
Role of Kisspeptin and Neurokinin B in Puberty in Female Non-Human Primates
Terasawa, E., Garcia, J. P., Seminara, S. B., & Keen, K. L. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00148 · Cited by 24 · see citing works
KNDy Hypothesis for Generation of GnRH Pulses: Evidence from Sheep and Goats
Goodman, R. L., Okhura, S., Okamura, H., Coolen, L. M., & Lehman, M. N. (2018) · Wiley eBooks · doi:10.1002/9781119233275.ch12 · Cited by 24 · see citing works
Arcuate nucleus neuropeptide coexpression and connections to gonadotrophin‐releasing hormone neurones in the female rhesus macaque
True, C. A., Takahashi, D. L., Kirigiti, M. A., Lindsley, S. R., Moctezuma, C., Arik, A. J., Smith, M. S., Kievit, P., & Grove, K. L. (2017) · Journal of Neuroendocrinology · doi:10.1111/jne.12491 · Cited by 24 · see citing works
The human hypothalamic kisspeptin system: Functional neuroanatomy and clinical perspectives
Hrabovszky, E., Takács, S., Rumpler, É., & Skrapits, K. (2021) · Handbook of clinical neurology · doi:10.1016/b978-0-12-820107-7.00017-3 · Cited by 19 · see citing works
The mechanism underlying the pubertal increase in pulsatile GnRH release in primates
Terasawa, E. (2022) · Journal of Neuroendocrinology · doi:10.1111/jne.13119 · Cited by 19 · see citing works
Lesions of KNDy and Kiss1R Neurons in the Arcuate Nucleus Produce Different Effects on LH Pulse Patterns in Female Sheep
Goodman, R. L., Moore, A. M., Onslow, K. M., Hileman, S. M., Hardy, S. L., Bowdridge, E. C., Walters, B. A., Ağuş, S., Griesgraber, M. J., Aerts, E. G., et al. (2023) · Endocrinology · doi:10.1210/endocr/bqad148 · Cited by 19 · see citing works
The 3rd World Conference on Kisspeptin, “Kisspeptin 2017: Brain and Beyond”: Unresolved questions, challenges and future directions for the field
Lehman, M. N., Coolen, L. M., Steiner, R. A., Neal-Perry, G. S., Wang, L., Moenter, S. M., Moore, A. M., Goodman, R. L., Yeo, S. ‐., Padilla, S. L., et al. (2018) · Journal of Neuroendocrinology · doi:10.1111/jne.12600 · Cited by 17 · see citing works
Undernutrition reduces kisspeptin and neurokinin B expression in castrated male sheep
Merkley, C. M., Renwick, A. N., Shuping, S. L., Harlow, K., Sommer, J. R., & Nestor, C. C. (2020) · Reproduction and Fertility · doi:10.1530/raf-20-0025 · Cited by 17 · see citing works
Role of Kisspeptin and NKB in Puberty in Nonhuman Primates: Sex Differences
Garcia, J. P., Keen, K. L., Seminara, S. B., & Terasawa, E. (2019) · Seminars in Reproductive Medicine · doi:10.1055/s-0039-3400253 · Cited by 16 · see citing works
Kisspeptin a potential therapeutic target in treatment of both metabolic and reproductive dysfunction
Sliwowska, J. H., Woods, N. E., Alzahrani, A. R., Paspali, E., Tate, R. J., & Ferro, V. A. (2024) · Journal of Diabetes · doi:10.1111/1753-0407.13541 · Cited by 17 · see citing works
Neuronal basis of reproductive dysfunctions associated with diet and alcohol: From the womb to adulthood
Gawałek, M., & Sliwowska, J. H. (2015) · Reproductive Biology · doi:10.1016/j.repbio.2015.04.001 · Cited by 15 · see citing works
Conditional Deletion of KOR (Oprk1) in Kisspeptin Cells Does Not Alter LH Pulses, Puberty, or Fertility in Mice
Coutinho, E. A., Esparza, L. A., Hudson, A. D., Rizo, N., Steffen, P., & Kauffman, A. S. (2022) · Endocrinology · doi:10.1210/endocr/bqac175 · Cited by 14 · see citing works
The impact of undernutrition on KNDy (kisspeptin/neurokinin B/dynorphin) neurons in female lambs
Harlow, K., Griesgraber, M. J., Seman, A., Shuping, S. L., Sommer, J. R., Griffith, E. H., Hileman, S. M., & Nestor, C. C. (2022) · Journal of Neuroendocrinology · doi:10.1111/jne.13135 · Cited by 14 · see citing works
Importance of neuroanatomical data from domestic animals to the development and testing of the KNDy hypothesis for GnRH pulse generation
Lehman, M. N., Coolen, L. M., & Goodman, R. L. (2020) · Domestic Animal Endocrinology · doi:10.1016/j.domaniend.2020.106441 · Cited by 13 · see citing works
Regulation of prepubertal dynorphin secretion in the medial basal hypothalamus of the female rat
Dees, W. L., Hiney, J. K., & Srivastava, V. K. (2019) · Journal of Neuroendocrinology · doi:10.1111/jne.12810 · Cited by 12 · see citing works
Effects of the Hormone Kisspeptin on Reproductive Hormone Release in Humans
Calley, J. L., & Dhillo, W. S. (2014) · Advances in Biology · doi:10.1155/2014/512650 · Cited by 12 · see citing works
Novel Biology of Tachykinins in Gonadotropin-Releasing Hormone Secretion
León, S., & Navarro, V. M. (2019) · Seminars in Reproductive Medicine · doi:10.1055/s-0039-3400252 · Cited by 12 · see citing works
Invited review: Translating kisspeptin and neurokinin B biology into new therapies for reproductive health
Mills, E., & Dhillo, W. S. (2022) · Journal of Neuroendocrinology · doi:10.1111/jne.13201 · Cited by 12 · see citing works
Kisspeptin in functional hypothalamic amenorrhea: Pathophysiology and therapeutic potential
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Immunoelectron microscopic observation of the subcellular localization of kisspeptin, neurokinin B and dynorphin A in KNDy neurons in the arcuate nucleus of the female rat
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Authors: 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., & Liposits, Z.
Affiliations: HUN-REN Institute of Experimental Medicine (HU)
Inserm (FR)
University of Debrecen (HU)
Hammersmith Hospital (GB)
Pázmány Péter Catholic University (HU)
Corresponding author: Hrabovszky, Erik
ORCID: Hrabovszky, Erik
Ciofi, Philippe
Borsay, Beáta Á.
Gergely, Péter
Bloom, Stephen R.
Dhillo, Waljit S.
Liposits, Zsolt
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 2012-10-01
Volume: 153
Issue: 10
Pages: 4978-4989
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/en.2012-1545
PMC: PMC3512020
OpenAlex: W2024088392
Cited by: 124
References: 66
Citations by year: 2026: 4 · 2025: 8 · 2024: 6 · 2023: 6 · 2022: 9 · 2021: 13 · 2020: 7 · 2019: 10 · 2018: 9 · 2017: 7 · 2016: 5 · 2015: 10 · 2014: 14 · 2013: 14 · 2012: 1
FWCI: 14.53
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Endocrinology (publishedVersion, public-domain)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion, other-oa)
University of Debrecen Electronic Archive (University of Debrecen) (submittedVersion, other-oa)
Funders: National Institute for Health and Care Research (CDF-2009-02-05)
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, neurokinin B, dynorphin A, KNDy neurons, arcuate nucleus, neuropeptide co-localization, GnRH neurons, reproductive control, human brain
MeSH terms: Adult, Arcuate Nucleus of Hypothalamus, Dynorphins, Humans, Gonadotropin-Releasing Hormone, Male, Nerve Fibers, Neurons, Neurokinin B, Kisspeptins

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Low degree of overlap between kisspeptin, neurokinin B, and dynorphin immunoreactivities in the infundibular nucleus of young male human subjects challenges the KNDy neuron concept

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