Involvement of anteroventral periventricular metastin/kisspeptin neurons in estrogen positive feedback action on luteinizing hormone release in female rats
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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 express ERα, and the kisspeptin receptor GPR54 is expressed in GnRH neurons.
“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
The KISS1 positive regulation is believed to be important for the LH surge in females of many mammalian species.
“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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- 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
- Social Sciences › Psychology › Social Psychology › 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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