Peripheral administration of metastin induces marked gonadotropin release and ovulation in the rat
Abstract
Metastin is a novel peptide that has been isolated from the human placenta as the cognate ligand of the G-protein-coupled receptor OT7T175 (or GPR54). However, its physiological functions have not yet been fully investigated. In the present study, we show that subcutaneous administration of metastin increased the plasma levels of gonadotropins (follicle-stimulating hormone and luteinizing hormone) and induced ovulation in prepubertal female rats that had been pretreated with pregnant mare serum gonadotropin to induce follicle maturation. Furthermore, metastin administration drastically increased the plasma levels of gonadotropins in male rats. This action was abolished by pretreatment with a GnRH antagonist, and was accompanied by induction of c-Fos immunoreactivity in GnRH neurons. These results suggest that s.c. administered metastin induces the release of gonadotropin via activation of the hypothalamic GnRH neurons.
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
Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54
de Roux, N., Genin, E., Carel, J.-C., Matsuda, F., Chaussain, J.-L., & Milgrom, E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1834399100 · Cited by 2,431 · see citing works
Kotani, M., Detheux, M., Vandenbogaerde, A., Communi, D., Vanderwinden, J.-M., Le Poul, E., Brézillon, S., Tyldesley, R., Suarez-Huerta, N., Vandeput, F., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104847200 · Cited by 1,546 · 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-citationKiSS-1, a Novel Human Malignant Melanoma Metastasis-Suppressor Gene
Lee, J.-H., Miele, M. E., Hicks, D. J., Phillips, K. K., Trent, J. M., Weissman, B. E., & Welch, D. R. (1996) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/88.23.1731 · Cited by 1,072 · 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
The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system
Funes, S., Hedrick, J. A., Vassileva, G., Markowitz, L., Abbondanzo, S., Golovko, A., Yang, S., Monsma, F. J., & Gustafson, E. L. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.11.066 · Cited by 675 · see citing works
Multimodal Influence of Estrogen upon Gonadotropin-Releasing Hormone Neurons
Herbison, A. E. (1998) · Endocrine Reviews · doi:10.1210/edrv.19.3.0332 · Cited by 618 · see citing works
Sensory circumventricular organs and brain homeostatic pathways
Johnson, A. K., & Gross, P. M. (1993) · The FASEB Journal · doi:10.1096/fasebj.7.8.8500693 · Cited by 511 · see citing works
Lee, J., & Welch, D. R. (1997) · PubMed · Cited by 371 · see citing works
Horikoshi, 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-citationLee, W.-S., Smith, M. S., & Hoffman, G. E. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.13.5163 · Cited by 272 · see citing works
Urbanski, H. F., & Ojeda, S. R. (1990) · Endocrinology · doi:10.1210/endo-126-3-1774 · Cited by 213 · see citing works
Stafford, L. J., Xia, C., Ma, W., Cai, Y., & Liu, M. (2002) · PubMed · Cited by 188 · 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-citationLee, J., & Welch, D. R. (1997) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19970611)71:6 · Cited by 172 · see citing works
Distribution of Galanin-Like Peptide in the Rat Brain
Takatsu, Y., Matsumoto, H., Ohtaki, T., Kumano, S., Kitada, C., Onda, H., Nishimura, O., & Fujino, M. (2001) · Endocrinology · doi:10.1210/endo.142.4.8089 · Cited by 154 · see citing works
Self-citationEndogenous GABA Release Inhibits the Firing of Adult Gonadotropin-Releasing Hormone Neurons
Han, S., Todman, M. G., & Herbison, A. E. (2003) · Endocrinology · doi:10.1210/en.2003-1333 · Cited by 147 · see citing works
Fortune, J. E., & Hansel, W. (1985) · Biology of Reproduction · doi:10.1095/biolreprod32.5.1069 · Cited by 146 · see citing works
Metastin Suppresses the Motility and Growth of CHO Cells Transfected with Its Receptor
Hori, A., Honda, S., Asada, M., Ohtaki, T., Oda, K., Watanabe, T., Shintani, Y., Yamada, T., Suenaga, M., Kitada, C., et al. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.5470 · Cited by 106 · see citing works
Self-citationBrann, D. W., & Mahesh, V. B. (2008) · Neuroendocrinology · doi:10.1159/000125706 · Cited by 45 · see citing works
Veneroni, O., Cocilovo, L., Müller, E. E., & Cocchi, D. (1990) · Life Sciences · doi:10.1016/0024-3205(90)90218-g · Cited by 32 · see citing works
Attardi, B., Klatt, B. A., Hoffman, G. E., et al. (1997) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.1997.00610.x · Cited by 31 · see citing works
Funabashi, T., Jinnai, K., & Kimura, F. (1997) · Neuroreport · doi:10.1097/00001756-199702100-00038 · Cited by 31 · see citing works
Ping, L., Mahesh, V. B., & Brann, D. W. (1994) · Endocrinology · doi:10.1210/endo.135.1.7912182 · Cited by 29 · see citing works
Matsumoto, H., Suzuki, N., Shiota, K., et al. (1990) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(90)90725-3 · Cited by 25 · see citing works
Self-citationFunabashi, T., Jinnai, K., & Kimura, F. (1997) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.1997.00550.x · Cited by 20 · see citing works
Mitsushima, D., Funabashi, T., & Kimura, F. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01758-8 · Cited by 16 · see citing works
Dumesic, D. A., Renk, M., & Kamel, F. (1989) · Life Sciences · doi:10.1016/0024-3205(89)90264-6 · Cited by 12 · see citing works
The role of tyrosine kinase in gonadotropin-induced ovulation in the rat ovary
Shimamoto, T., Yamoto, M., & Nakano, R. (1998) · European Journal of Endocrinology · doi:10.1530/eje.0.1380594 · Cited by 6 · see citing works
Nishimura, O., Suenaga, M., Yamada, T., et al. (2001) · Journal of the Chemical Society Perkin Transactions 1 · doi:10.1039/b104948h · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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 · 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 · 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-citationKinoshita, M., Tsukamura, H., Adachi, S., Matsui, H., Uenoyama, Y., Iwata, K., Yamada, S., Inoue, K., Ohtaki, T., Matsumoto, H., et al. (2005) · Endocrinology · doi:10.1210/en.2005-0195 · Cited by 507 · see citing works
Self-citationSmith, J. T., Clay, C. M., Caraty, A., & Clarke, I. J. (2007) · Endocrinology · doi:10.1210/en.2006-1435 · Cited by 404 · see citing works
The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism
Bianco, S. D. C., & Kaiser, U. B. (2009) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2009.177 · Cited by 336 · 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
Caraty, A., Smith, J. T., Lomet, D., Ben Saïd, S., Morrissey, A., Cognie, J., Doughton, B., Baril, G., Briant, C., & Clarke, I. J. (2007) · Endocrinology · doi:10.1210/en.2007-0554 · Cited by 313 · see citing works
Semple, R. K., Achermann, J. C., Ellery, J., Farooqi, I. S., Karet, F. E., Stanhope, R. G., O’Rahilly, S., & Aparicio, S. A. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1418 · Cited by 291 · 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
Tenenbaum-Rakover, Y., Commenges-Ducos, M., Iovane, A., Aumas, C., Admoni, O., & de Roux, N. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-2147 · Cited by 169 · see citing works
The recent genetics of hypogonadotrophic hypogonadism—novel insights and new questions
Semple, R. K., & Topaloglu, A. K. (2010) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2009.03687.x · Cited by 117 · 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
Estrogen Regulates KiSS1 Gene Expression through Estrogen Receptor α and SP Protein Complexes
Li, D., Mitchell, D., Luo, J., Yi, Z., Cho, S.-G., Guo, J., Li, X., Ning, G., Wu, X., & Liu, M. (2007) · Endocrinology · doi:10.1210/en.2007-0154 · Cited by 90 · 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
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
From engineering to editing the rat genome
Meek, S., Mashimo, T., & Burdon, T. (2017) · Mammalian Genome · doi:10.1007/s00335-017-9705-8 · Cited by 63 · see citing works
Smith, J. T. (2012) · Domestic Animal Endocrinology · doi:10.1016/j.domaniend.2011.11.003 · Cited by 55 · 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
GnRH receptor and GPR54 inactivation in isolated gonadotropic deficiency
de Roux, N. (2006) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2006.10.005 · Cited by 35 · see citing works
- Authors
- Matsui, H., Takatsu, Y., Kumano, S., Matsumoto, H., & Ohtaki, T.
- Affiliations
- Takeda (Japan) (JP)
- Corresponding author
- Ohtaki, Tetsuya
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2004-07
- Volume
- 320
- Issue
- 2
- Pages
- 383-388
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2021996823
- Cited by
- 520
- References
- 31
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 8 · 2023: 7 · 2022: 17 · 2021: 22 · 2020: 14 · 2019: 13 · 2018: 23 · 2017: 21 · 2016: 25 · 2015: 18 · 2014: 30 · 2013: 36 · 2012: 34
- FWCI
- 29.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (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, GPR54, gonadotropin secretion, ovulation, follicle-stimulating hormone, luteinizing hormone, GnRH neurons, c-fos, hypothalamus, GnRH antagonist, peripheral administration, prepubertal female rats, male rats
- MeSH terms
- Animals, Gonadotropins, Male, Ovulation, Pituitary Gland, Anterior, Proto-Oncogene Proteins c-fos, Rats, Wistar, Rats
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