Cited by 507Hypothalamic control of reproductive hormonesReproductive Biology and FertilityNeuropeptides and Animal Physiology

Involvement of central metastin in the regulation of preovulatory luteinizing hormone surge and estrous cyclicity in female rats

Kinoshita, Mika, Tsukamura, Hiroko, Adachi, Sachika, Matsui, Hisanori, Uenoyama, Yoshihisa, Iwata, Kinuyo, Yamada, Shunji, Inoue, Kinji +3 more·2005·Endocrinology

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.

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Crossref · 10.1210/en.2005-0195

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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
Venue
Endocrinology
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

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