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Menstrual cyclic change of metastin/GPR54 in endometrium

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Abstract

Metastin/kisspeptin is encoded by KISS1 and functions as an endogenous ligand of GPR54. Interaction of metastin with GPR54 suppresses metastasis and also regulates release of gonadotropin-releasing hormone, which promotes secretion of estradiol (E2) and progesterone (P4). We have previously demonstrated epigenetic regulation of GPR54 in endometrial cancer and the potent role of metastin peptides in inhibiting metastasis in endometrial cancer. However, little is known about how the metastin–GPR54 axis is regulated in the endometrium, the precursor tissue of endometrial cancer. Endometrial stromal cells (ESCs) and endometrial glandular cells (EGCs) within the endometrium show morphological changes when exposed to E2 and P4. In this study, we show that metastin expression is induced in ESCs through decidualization, but is repressed in glandular components of atypical endometrial hyperplasia (AEH) and endometrial cancer relative to EGCs. The promoter of GPR54 is unmethylated in normal endometrium and in AEH. These results indicate metastin may function in decidualized endometrium to prepare for adequate placentation but this autocrine secretion of metastin is deregulated during oncogenesis to enable tumor cells to spread.

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Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Tsukasa Baba, Hyun Sook Kang, Yuko Hosoe, Budiman Kharma, Kaoru Abiko, Noriomi Matsumura, Junzo Hamanishi, Ken Yamaguchi, Yumiko Yoshioka, Masafumi Koshiyama & Ikuo Konishi

  2. Department of Obstetrics and Gynecology, Faculty of Medicine, Kinki University, Osaka, Japan

    Masaki Mandai

  3. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA

    Susan K. Murphy

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  1. Tsukasa Baba
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  2. Hyun Sook Kang
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  3. Yuko Hosoe
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  4. Budiman Kharma
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Correspondence to Tsukasa Baba.

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Baba, T., Kang, H.S., Hosoe, Y. et al. Menstrual cyclic change of metastin/GPR54 in endometrium. Med Mol Morphol 48, 76–84 (2015). https://doi.org/10.1007/s00795-014-0081-0

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  • DOI: https://doi.org/10.1007/s00795-014-0081-0

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