Involvement of central metastin in the regulation of preovulatory luteinizing hormone surge and estrous cyclicity in female rats
Abstract
Ovulation is caused by a sequence of neuroendocrine events: GnRH and LH surges that are induced by positive feedback action of estrogen secreted by the mature ovarian follicles. The central mechanism of positive feedback action of estrogen on GnRH/LH secretion, however, is not fully understood yet. The present study examined whether metastin, the product of metastasis suppressor gene KiSS-1, is a central neuropeptide regulating GnRH/LH surge and then estrous cyclicity in the female rat. Metastin had a profound stimulation on LH secretion by acting on the preoptic area (POA), where most GnRH neurons projecting to the median eminence are located, because injection of metastin into the third ventricle or POA increased plasma LH concentrations in estrogen-primed ovariectomized rats. Metastin neurons were immunohistochemically found in the arcuate nucleus (ARC) to be colocalized with estrogen receptors with some fibers in the preoptic area (POA) in close apposition with GnRH neuronal cell bodies or fibers. Quantitative RT-PCR has revealed that KiSS-1 and GPR54 mRNAs were expressed in the ARC and POA, respectively. The blockade of local metastin action in the POA with a specific monoclonal antibody to rat metastin completely abolished proestrous LH surge and inhibited estrous cyclicity. Metastin-immunoreactive cell bodies in the ARC showed a marked increase and c-Fos expression in the early proestrus afternoon compared with the day of diestrus. Thus, metastin released in the POA is involved in inducing the preovulatory LH surge and regulating estrous cyclicity.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Cites
The <i>GPR54</i> Gene as a Regulator of Puberty
Seminara, S. B., Messager, S., Chatzidaki, E. E., Thresher, R. R., Acierno, J. S., Shagoury, J. K., Bo-Abbas, Y., Kuohung, W., Schwinof, K. M., Hendrick, A. G., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa035322 · Cited by 2,557 · see citing works
Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor
Ohtaki, T., Shintani, Y., Honda, S., Matsumoto, H., Hori, A., Kanehashi, K., Terao, Y., Kumano, S., Takatsu, Y., Masuda, Y., et al. (2001) · Nature · doi:10.1038/35079135 · Cited by 1,447 · see citing works
Self-citationMessager, S., Chatzidaki, E. E., Ma, D., Hendrick, A. G., Zahn, D., Dixon, J., Thresher, R. R., Malinge, I., Lomet, D., Carlton, M. B. L., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409330102 · Cited by 1,215 · see citing works
A role for kisspeptins in the regulation of gonadotropin secretion in the mouse
Gottsch, M. L., Cunningham, M. J., Smith, J. T., Popa, S. M., Acohido, B. V., Crowley, W. F., Seminara, S., Clifton, D. K., & Steiner, R. A. (2004) · Endocrinology · doi:10.1210/en.2004-0431 · Cited by 1,161 · see citing works
Irwig, M. S., Fraley, G. S., Smith, J. T., Acohido, B. V., Popa, S. M., Cunningham, M. J., Gottsch, M. L., Clifton, D. K., & Steiner, R. A. (2004) · Neuroendocrinology · doi:10.1159/000083140 · Cited by 913 · see citing works
AXOR12, a Novel Human G Protein-coupled Receptor, Activated by the Peptide KiSS-1
Muir, A. I., Chamberlain, L., Elshourbagy, N. A., Michalovich, D., Moore, D. J., Calamari, A., Szekeres, P. G., Sarau, H. M., Chambers, J. K., Murdock, P. R., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102743200 · Cited by 906 · see citing works
Navarro, V. M., Castellano, J. M., Fernández-Fernández, R., Barreiro, M. L., Roa, J., Sanchez-Criado, J. E., Aguilar, E., Dieguez, C., Pinilla, L., & Tena-Sempere, M. (2004) · Endocrinology · doi:10.1210/en.2004-0413 · Cited by 711 · see citing works
Peripheral administration of metastin induces marked gonadotropin release and ovulation in the rat
Matsui, H., Takatsu, Y., Kumano, S., Matsumoto, H., & Ohtaki, T. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.05.185 · Cited by 520 · see citing works
Self-citationHorikoshi, Y., Matsumoto, H., Takatsu, Y., Ohtaki, T., Kitada, C., Usuki, S., & Fujino, M. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021235 · Cited by 324 · see citing works
Self-citationA sensitive sandwich-enzyme immunoassay for human endothelin
Suzuki, N., Matsumoto, H., Kitada, C., et al. (1989) · Journal of Immunological Methods · doi:10.1016/0022-1759(89)90012-4 · Cited by 290 · see citing works
Self-citationHrabovszky, E., Shughrue, P. J., Merchenthaler, I. J., Hajszán, T., Carpenter, C. D., Liposits, Z., & Petersen, S. L. (2000) · Endocrinology · doi:10.1210/endo.141.9.7788 · Cited by 279 · see citing works
New Evidence for Estrogen Receptors in Gonadotropin-Releasing Hormone Neurons
Herbison, A. E., & Pape, J. (2001) · Frontiers in Neuroendocrinology · doi:10.1006/frne.2001.0219 · Cited by 257 · see citing works
The Site of the Positive Feedback Action of Estradiol in the Rat*
Goodman, R. L. (1978) · Endocrinology · doi:10.1210/endo-102-1-151 · Cited by 195 · see citing works
Caraty, A., Fabre‐Nys, C., Delaleu, B., Locatelli, A., Bruneau, G., Karsch, F. J., & Herbison, A. E. (1998) · Endocrinology · doi:10.1210/endo.139.4.5904 · Cited by 191 · see citing works
Expression of KiSS-1, a metastasis suppressor gene, in trophoblast giant cells of the rat placenta
Terao, Y., Kumano, S., Takatsu, Y., Hattori, M., Nishimura, A., Ohtaki, T., & Shintani, Y. (2004) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/j.bbaexp.2004.02.005 · Cited by 187 · see citing works
Self-citationCagampang, F. R. A., Maeda, K., Tsukamura, H., Ohkura, S., & Ôta, K. (1991) · Journal of Endocrinology · doi:10.1677/joe.0.1290321 · Cited by 180 · see citing works
Self-citationEstrogen Induction of LH Release in the Rhesus Monkey12
YAMAJI, T., Dierschke, D. J., Hotchkiss, J., et al. (1971) · Endocrinology · doi:10.1210/endo-89-4-1034 · Cited by 149 · see citing works
Naftolin, F. N., Mor, G., Horváth, T. L., Luquı́n, S., Fajer, A. B., Kohen, F., & García‐Segura, L. M. (1996) · Endocrinology · doi:10.1210/endo.137.12.8940386 · Cited by 95 · see citing works
Matsumoto, H., Murakami, Y., Horikoshi, Y., et al. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0463 · Cited by 77 · see citing works
Self-citationTsukamura, H., Maeda, K., & Yokoyama, A. (1988) · Journal of Endocrinology · doi:10.1677/joe.0.1180311 · Cited by 59 · see citing works
Self-citationGoubillon, M.-L., Delaleu, B., Tillet, Y., Caraty, A., & Herbison, A. E. (1999) · Neuroendocrinology · doi:10.1159/000054481 · Cited by 55 · see citing works
Clarke, I. J., Pompolo, S., Scott, C., Rawson, J. A., Caddy, D. J., Jakubowska, A. E., & Pereira, A. (2001) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.2001.00694.x · Cited by 46 · see citing works
Horváth, T. L., García‐Segura, L. M., & Naftolin, F. N. (2008) · Neuroendocrinology · doi:10.1159/000127173 · Cited by 31 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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 · see citing works
Lehman, M. N., Coolen, L. M., & Goodman, R. L. (2010) · Endocrinology · doi:10.1210/en.2010-0022 · Cited by 768 · see citing works
Kisspeptin 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 · see citing works
Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males
Dhillo, W. S., Chaudhri, O. B., Patterson, M., Thompson, E. L., Murphy, K. G., Badman, M. K., McGowan, B. M., Amber, V., Patel, S., Ghatei, M. A., et al. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-1468 · Cited by 656 · see citing works
ADACHI, S., YAMADA, S., TAKATSU, Y., MATSUI, H., KINOSHITA, M., TAKASE, K., SUGIURA, H., OHTAKI, T., MATSUMOTO, H., UENOYAMA, Y., et al. (2007) · Journal of Reproduction and Development · doi:10.1262/jrd.18146 · Cited by 580 · see citing works
Self-citationRometo, A. M., Krajewski, S. J., Lou Voytko, M., & Rance, N. E. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-0553 · Cited by 396 · see citing works
Herbison, A. E. (2008) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.05.006 · Cited by 351 · see citing works
Sex differences in circadian timing systems: implications for disease
Bailey, M., & Silver, R. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2013.11.003 · Cited by 348 · see citing works
Hrabovszky, E., Ciofi, P., Vida, B., Horvath, M. C., Keller, E., Caraty, A., Bloom, S. R., Ghatei, M. A., Dhillo, W. S., Liposits, Z., et al. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07239.x · Cited by 314 · see citing works
Rance, N. E. (2009) · Peptides · doi:10.1016/j.peptides.2008.05.016 · Cited by 237 · see citing works
Kinsey‐Jones, J. S., Li, X. F., Knox, A. M. I., Wilkinson, E. S., Zhu, X. L., Chaudhary, A. A., Milligan, S. R., Lightman, S. L., & O’Byrne, K. T. (2009) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2008.01807.x · Cited by 196 · see citing works
Robertson, J. L., Clifton, D. K., de la Iglesia, H. O., Steiner, R. A., & Kauffman, A. S. (2009) · Endocrinology · doi:10.1210/en.2009-0247 · Cited by 189 · 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
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
Coming of age in the Kisspeptin Era: Sex differences, development, and puberty
Kauffman, A. S. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.01.017 · Cited by 106 · see citing works
Estrogenic Regulation of the GnRH Neuron
Radovick, S., Levine, J. E., & Wolfe, A. (2012) · Frontiers in Endocrinology · doi:10.3389/fendo.2012.00052 · Cited by 102 · see citing works
Khan, A. R., & Kauffman, A. S. (2012) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2011.02162.x · Cited by 99 · see citing works
Kisspeptin regulates prolactin release through hypothalamic dopaminergic neurons
Szawka, R. E., Ribeiro, A. B., Leite, C. M., Helena, C. V. V., Franci, C. R., Anderson, G. M., Hoffman, G. E., & Anselmo-Franci, J. A. (2010) · Endocrinology · doi:10.1210/en.2009-1414 · Cited by 97 · see citing works
Kisspeptin and seasonality in sheep
Clarke, I. J., Smith, J. T., Caraty, A., Goodman, R. L., & Lehman, M. N. (2009) · Peptides · doi:10.1016/j.peptides.2008.08.022 · Cited by 96 · see citing works
Ohkura, S., Uenoyama, Y., Yamada, S., Homma, T., Takase, K., Inoue, N., Maeda, K.-I., & Tsukamura, H. (2009) · Peptides · doi:10.1016/j.peptides.2008.08.004 · Cited by 80 · see citing works
Self-citationKisspeptin-neuron control of LH pulsatility and ovulation
Stevenson, H., Bartram, S., Charalambides, M. M., Murthy, S., Petitt, T., Pradeep, A., Vineall, O., Abaraonye, I., Lancaster, A., Koysombat, K., et al. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.951938 · Cited by 48 · see citing works
Kisspeptin Overcomes GnRH Neuronal Suppression Secondary to Hyperprolactinemia in Humans
Hoskova, K., Kayton Bryant, N., Chen, M. E., Nachtigall, L. B., Lippincott, M. F., Balasubramanian, R., & Seminara, S. B. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac166 · Cited by 39 · see citing works
Zhuo, Y., Zhou, D., Che, L., Fang, Z., Lin, Y., & Wu, D. (2014) · Nutrition · doi:10.1016/j.nut.2013.12.019 · Cited by 33 · see citing works
- Authors
- Kinoshita, M., Tsukamura, H., Adachi, S., Matsui, H., Uenoyama, Y., Iwata, K., Yamada, S., Inoue, K., Ohtaki, T., Matsumoto, H., & Maeda, K.-I.
- Affiliations
- Nagoya University (JP)
- Saitama University (JP)
- Takeda (Japan) (JP)
- Corresponding author
- Maeda, Kei-Ichiro
- ORCID
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2005-10
- Volume
- 146
- Issue
- 10
- Pages
- 4431-4436
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2155941020
- Cited by
- 507
- References
- 23
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 6 · 2023: 17 · 2022: 27 · 2021: 19 · 2020: 14 · 2019: 16 · 2018: 25 · 2017: 16 · 2016: 27 · 2015: 24 · 2014: 26 · 2013: 45 · 2012: 38
- FWCI
- 32.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- kisspeptin, KISS1, GPR54, luteinizing hormone surge, estrous cyclicity, preoptic area, arcuate nucleus, estrogen receptor, GnRH neurons, ovulation, c-fos, female rats
- MeSH terms
- Animals, Antibodies, Monoclonal, Estrus, Female, Homeostasis, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Ovariectomy, Proteins, Rats, Wistar, DNA Primers, Reverse Transcriptase Polymerase Chain Reaction, Tumor Suppressor Proteins, Rats, Kisspeptins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review