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Involvement of Anteroventral Periventricular Metastin/Kisspeptin Neurons in Estrogen Positive Feedback Action on Luteinizing Hormone Release in Female Rats
Open accessAbstract
Metastin/kisspeptin, the KiSS-1 gene product, has been identified as an endogenous ligand of GPR54 that reportedly regulates GnRH/LH surges and estrous cyclicity in female rats. The aim of the present study was to determine if metastin/kisspeptin neurons are a target of estrogen positive feedback to induce GnRH/LH surges. We demonstrated that preoptic area (POA) infusion of the anti-rat metastin/kisspeptin monoclonal antibody blocked the estrogen-induced LH surge, indicating that endogenous metastin/kisspeptin released around the POA mediates the estrogen positive feedback effect on GnRH/LH release. Metastin/kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) may be responsible for mediating the feedback effect because the percentage of c-Fos-expressing KiSS-1 mRNA-positive cells to total KiSS-1 mRNA-positive cells was significantly higher in the afternoon than in the morning in the anteroventral periventricular nucleus (AVPV) of high estradiol (E(2))-treated females. The percentage of c-Fos-expressing metastin/kisspeptin neurons was not different between the afternoon and morning in the arcuate nucleus (ARC). Most of the KiSS-1 mRNA expressing cells contain ERalpha immunoreactivity in the AVPV and ARC. In addition, AVPV KiSS-1 mRNA expressions were highest in the proestrous afternoon and lowest in the diestrus 1 in females and were increased by estrogen treatment in ovariectomized animals. On the other hand, the ARC KiSS-1 mRNA expressions were highest at diestrus 2 and lowest at proestrous afternoon and were increased by ovariectomy and decreased by high estrogen treatment. Males lacking the surge mode of GnRH/LH release showed no obvious cluster of metastin/kisspeptin-immunoreactive neurons in the AVPV when compared with high E(2)-treated females, which showed a much greater density of these neurons. Taken together, the present study demonstrates that the AVPV metastin/kisspeptin neurons are a target of estrogen positive feedback to induce GnRH/LH surges in female rats.
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“Kisspeptin neurons have been shown to express ERα (Adachi et al., 2007; Clarkson, d’Anglemont de Tassigny, Moreno, Colledge, & Herbison, 2008; Franceschini et al., 2006) and the kisspeptin receptor GPR54 is expressed in GnRH neurons (Clements et al., 2001; Kotani et al., 2001; Muir et al., 2001; Ohtaki et al., 2001).”
From Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity (2017) · cites this paper as Adachi et al., 2007
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“The KISS1 positive regulation is believed to be important for the LH surge in females of many mammalian species.61”
From Pubertal development and regulation (2016) · cites this paper as [61]
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Metadata
- Authors
- ADACHI, S., YAMADA, S., TAKATSU, Y., MATSUI, H., KINOSHITA, M., TAKASE, K., SUGIURA, H., OHTAKI, T., MATSUMOTO, H., UENOYAMA, Y., TSUKAMURA, H., INOUE, K., & MAEDA, K.-I.
- Affiliations
- Saitama University (JP)
- Nagoya University (JP)
- Takeda (Japan) (JP)
- National Institute for Basic Biology (JP)
- ORCID
- Venue
- Journal of Reproduction and Development
- Published
- 2007
- Volume
- 53
- Issue
- 2
- Pages
- 367-378
- ISSN
- 0916-8818 (ISSN-L)
- 1348-4400
- OpenAlex
- W1984902037
- Cited by
- 580
- References
- 25
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 21 · 2023: 25 · 2022: 35 · 2021: 27 · 2020: 30 · 2019: 23 · 2018: 33 · 2017: 30 · 2016: 31 · 2015: 29 · 2014: 40 · 2013: 49 · 2012: 42
- FWCI
- 38.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Journal of Reproduction and Development (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (18658106)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- KISS1, anteroventral periventricular nucleus, estrogen positive feedback, luteinizing hormone surge, preoptic area, arcuate nucleus, estrous cycle, estradiol, GPR54, c-fos, estrogen receptor alpha, ovariectomy, female reproduction
- MeSH terms
- Receptors, Kisspeptin-1, Animals, Antibodies, Monoclonal, Arcuate Nucleus of Hypothalamus, Estradiol, Estrogens, Female, Gene Expression Regulation, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Male, Neurons, Preoptic Area, Proteins, Proto-Oncogene Proteins c-fos, Rats, Wistar, Anterior Thalamic Nuclei, Feedback, Physiological, Estrous Cycle, Receptors, G-Protein-Coupled, Estrogen Receptor alpha, Rats, Kisspeptins
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