Origin of luteinizing hormone-releasing hormone neurons
Abstract
Neurons expressing luteinizing hormone-releasing hormone (LHRH), found in the septal-preoptic nuclei and hypothalamus, control the release of gonadotropic hormones from the anterior pituitary gland and facilitate reproductive behaviour. LHRH-expressing neurons are also found in the nervus terminalis, a cranial nerve that is a part of the accessory olfactory system and which projects directly from the nose to the septal-preoptic nuclei in the brain. During development, LHRH-immunoreactivity is detected in the peripheral parts of the nervus terminalis before it is found in the brain. Using a combination of LHRH immunocytochemistry and tritiated thymidine autoradiography in fetal mice, we show that LHRH neurons originate in the medial olfactory placode of the developing nose, migrate across the nasal septum and enter the forebrain with the nervus terminalis, arching into the septal-preoptic area and hypothalamus. Clinically, this migratory route for LHRH-expressing neurons could explain the deficiency of gonadotropins seen in 'Kallmann's syndrome' (hypogonadotropic hypogonadism with anosmia).
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GnRH neurons arise in the nasal placode and migrate into the brain along the vomeronasal nerve to their adult location in the hypothalamus.
“GnRH neurons have a very curious lifespan, arising in the nasal placode in early development and then migrating into the brain along the vomeronasal nerve to eventually take up their adult location in the hypothalamus (Schwanzel-Fukuda & Pfaff, 1989; Tobet & Schwarting, 2006; Wray, Nieburgs, & Elkabes, 1989).”
From Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity (2017) · cites this paper as Schwanzel-Fukuda & Pfaff, 1989
The nervus terminalis appears to be the pathway for migration of LHRH (GnRH) neurons into the brain from the olfactory/vomeronasal epithelium early in development, in humans as in other species.
“The nerve appears to be the pathway for migration of LHRH (GnRH) neurons into the brain from the olfactory/vomeronasal epithelium early in development, in humans as in other species (Schwanzel-Fukuda and Pfaff, 1989;Ronkliev and Resko, 1990;Boehm et al., 1994).”
From Human Vomeronasal Organ Function: A Critical Review of Best and Worst Cases (2001) · cites this paper as Schwanzel-Fukuda and Pfaff, 1989
Cites
The development of the nervus terminalis in man
Pearson, A. A. (1941) · Journal of Comparative Neurology · doi:10.1002/cne.900750104 · Cited by 119 · see citing works
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Franco, B., Guioli, S., Pragliola, A., Incerti, B., Bardoni, B., Tonlorenzi, R., Carrozzo, R., Maestrini, E., Pieretti, M., Taillon-Miller, P., et al. (1991) · Nature · doi:10.1038/353529a0 · Cited by 846 · see citing works
Schnaar, R. L., Gerardy-Schahn, R., & Hildebrandt, H. (2014) · Physiological Reviews · doi:10.1152/physrev.00033.2013 · Cited by 745 · see citing works
Oyola, M. G., & Handa, R. J. (2017) · Stress · doi:10.1080/10253890.2017.1369523 · Cited by 710 · see citing works
“…have a very curious lifespan, arising in the nasal placode in early development and then migrating into the brain along the vomeronasal nerve to eventually take up their adult location in the hypothalamus (Schwanzel-Fukuda & Pfaff, 1989; Tobet & Schwarting, 2006; Wray, Nieburgs, & Elkabes, 1989).”
BackgroundLegouis, R., Hardelin, J.-P., Levilliers, J., Claverie, J.-M., Compain, S., Wunderle, V., Millasseau, P., Le Paslier, D., Cohen, D., & Caterina, D. (1991) · Cell · doi:10.1016/0092-8674(91)90193-3 · Cited by 678 · see citing works
Schwanzel-Fukuda, M., Bick, D., & Pfaff, D. W. (1989) · Molecular Brain Research · doi:10.1016/0169-328x(89)90076-4 · Cited by 616 · see citing works
Self-citationCimino, I., Casoni, F., Liu, X., Messina, A., Parkash, J., Jamin, S. P., Catteau-Jonard, S., Collier, F., Baroncini, M., Dewailly, D., et al. (2016) · Nature Communications · doi:10.1038/ncomms10055 · Cited by 404 · see citing works
Human Vomeronasal Organ Function: A Critical Review of Best and Worst Cases
Meredith, M. (2001) · Chemical Senses · doi:10.1093/chemse/26.4.433 · Cited by 280 · see citing works
Depew, M. J., Tucker, A. S., & Sharpe, P. T. (2002) · Mouse Development · doi:10.1016/b978-012597951-1/50023-8 · Cited by 259 · see citing works
Neural crest origin of olfactory ensheathing glia
Barraud, P., Seferiadis, A. A., Tyson, L. D., Zwart, M. F., Szabo-Rogers, H. L., Ruhrberg, C., Liu, K. J., & Baker, C. V. H. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1012248107 · Cited by 225 · see citing works
SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with Kallmann syndrome
Hanchate, N. K., Giacobini, P., Lhuillier, P., Parkash, J., Espy, C., Fouveaut, C., Leroy, C., Baron, S., Campagne, C., Vanacker, C., et al. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002896 · Cited by 217 · see citing works
Lanciotti, L., Cofini, M., Leonardi, A., Penta, L., & Esposito, S. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00410 · Cited by 209 · see citing works
Pitteloud, N., Meysing, A., Quinton, R., Acierno, J. S., Dwyer, A. A., Plummer, L., Fliers, E., Boepple, P., Hayes, F., Seminara, S., et al. (2006) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2006.04.021 · Cited by 198 · see citing works
Zecevic, N., & Verney, C. (1995) · Journal of Comparative Neurology · doi:10.1002/cne.903510404 · Cited by 149 · see citing works
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Albuisson, J., Pêcheux, C., Carel, J.-C., Lacombe, D., Leheup, B., Lapuzina, P., Bouchard, P., Legius, E., Matthijs, G., Wasniewska, M., et al. (2005) · Human Mutation · doi:10.1002/humu.9298 · Cited by 146 · see citing works
Abreu, A. P., Trarbach, E. B., de Castro, M., Frade Costa, E. M., Versiani, B., Matias Baptista, M. T., Garmes, H. M., Mendonca, B. B., & Latronico, A. C. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0958 · Cited by 122 · see citing works
Embryonic expression of tenascin-X suggests a role in limb, muscle, and heart development
Burch, G. H., Bedolli, M. A., McDonough, S., Rosenthal, S. M., & Bristow, J. (1995) · Developmental Dynamics · doi:10.1002/aja.1002030411 · Cited by 105 · see citing works
Kim, S. ‐., Hu, Y., Cadman, S., & Bouloux, P. (2008) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2007.01627.x · Cited by 87 · see citing works
Lhx2, an evolutionarily conserved, multifunctional regulator of forebrain development
Chou, S.-J., & Tole, S. (2019) · Brain Research · doi:10.1016/j.brainres.2018.02.046 · Cited by 74 · see citing works
Wolfe, A., Divall, S., & Wu, S. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.05.007 · Cited by 83 · see citing works
Functionally compromised <i>CHD7</i> alleles in patients with isolated GnRH deficiency
Balasubramanian, R., Choi, J.-H., Francescatto, L., Willer, J., Horton, E. R., Asimacopoulos, E. P., Stankovic, K. M., Plummer, L., Buck, C. L., Quinton, R., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1417438111 · Cited by 83 · see citing works
Gill, J. C., Moenter, S. M., & Tsai, P.-S. (2004) · Endocrinology · doi:10.1210/en.2004-0214 · Cited by 81 · see citing works
Reversible Kallmann syndrome: report of the first case with a KAL1 mutation and literature review
Ribeiro, R. S., Vieira, T. C., & Abucham, J. (2007) · European Journal of Endocrinology · doi:10.1530/eje.1.02342 · Cited by 71 · see citing works
Kallmann’s syndrome, a neuronal migration defect
Cariboni, A., & Maggi, R. (2006) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-005-5604-3 · Cited by 65 · see citing works
Luteinizing hormone-releasing hormone (LHRH)-expressing cells in the nasal septum of human fetuses
Boehm, N., Roos, J., & Gasser, B. (1994) · Developmental Brain Research · doi:10.1016/0165-3806(94)90160-0 · Cited by 54 · see citing works
Development of the gonadotropin‐releasing hormone system
Duittoz, A. H., Forni, P. E., Giacobini, P., Golan, M., Mollard, P., Negrón, A. L., Radovick, S., & Wray, S. (2022) · Journal of Neuroendocrinology · doi:10.1111/jne.13087 · Cited by 50 · see citing works
Stamou, M. I., Cox, K. H., & Crowley, W. F. (2015) · Endocrine Reviews · doi:10.1210/er.2015-1045.2016.1.test · Cited by 32 · see citing works
TAM Signaling in the Nervous System
Burstyn-Cohen, T., & Hochberg, A. (2021) · Brain Plasticity · doi:10.3233/bpl-210125 · Cited by 29 · see citing works
Derouiche, L., Keller, M., Martini, M., Duittoz, A. H., & Pillon, D. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00463 · Cited by 21 · see citing works
- Authors
- Schwanzel-Fukuda, M., & Pfaff, D. W.
- Affiliations
- Rockefeller University (US)
- ORCID
- Pfaff, Donald W.
- Venue
- Nature
- Published
- 1989-03
- Volume
- 338
- Issue
- 6211
- Pages
- 161-164
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2029618197
- Cited by
- 1,116
- References
- 1
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 22 · 2023: 34 · 2022: 24 · 2021: 35 · 2020: 25 · 2019: 18 · 2018: 32 · 2017: 25 · 2016: 23 · 2015: 35 · 2014: 31 · 2013: 31 · 2012: 24
- FWCI
- 44.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Keywords
- gonadotropin-releasing hormone, GnRH neurons, neuronal origin, terminal nerve, hypothalamus, neuronal migration, gonadotropin deficiency, Kallmann syndrome, anosmia, reproductive behavior, fetal development, mice
- MeSH terms
- Animals, Autoradiography, Brain Chemistry, Immunoenzyme Techniques, Gonadotropin-Releasing Hormone, Neural Pathways, Neurons, Olfactory Bulb, Mice
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