Menstrual cyclic change of metastin/GPR54 in endometrium

Journal Article

© 2014, The Japanese Society for Clinical Molecular Morphology. 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.

Full Text

Duke Authors

Cited Authors

  • Baba, T; Kang, HS; Hosoe, Y; Kharma, B; Abiko, K; Matsumura, N; Hamanishi, J; Yamaguchi, K; Yoshioka, Y; Koshiyama, M; Mandai, M; Murphy, SK; Konishi, I

Published Date

  • June 1, 2015

Published In

Volume / Issue

  • 48 / 2

Start / End Page

  • 76 - 84

Electronic International Standard Serial Number (EISSN)

  • 1860-1499

International Standard Serial Number (ISSN)

  • 1860-1480

Digital Object Identifier (DOI)

  • 10.1007/s00795-014-0081-0

Citation Source

  • Scopus