Expression of KiSS-1, a metastasis suppressor gene, in trophoblast giant cells of the rat placenta

• Published in: Biochimica et biophysica acta 2004-05, Vol.1678 (2), p.102-110
• Main Authors: Terao, Yasuko, Kumano, Satoshi, Takatsu, Yoshihiro, Hattori, Masahiko, Nishimura, Atsushi, Ohtaki, Tetsuya, Shintani, Yasushi
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; CHO Cells; Cloning, Molecular; Cricetinae; Disulfides; DNA, Complementary - metabolism; Dose-Response Relationship, Drug; Embryo Implantation; Embryo, Mammalian - metabolism; Genes, Tumor Suppressor; Giant Cells - metabolism; Implantation; In Situ Hybridization; KiSS-1; Kisspeptins; Metastin; Mice; Molecular Sequence Data; Neoplasm Metastasis; OT7T175; Peptides - chemistry; Placenta; Placenta - metabolism; Protein Biosynthesis; Proteins - genetics; Proteins - physiology; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Sequence Analysis, DNA; Time Factors; Tissue Distribution; Trophoblast giant cell; Trophoblasts - metabolism
• ISSN: 0167-4781; 0006-3002; 1879-2634
• DOI: 10.1016/j.bbaexp.2004.02.005

Metastin is encoded by a putative human metastasis suppressor gene KiSS-1, and is the cognate ligand of a G-protein-coupled receptor designated OT7T175. To study the physiological function(s) of metastin, we cloned rat and mouse KiSS-1 cDNAs both encoding 130-amino acid KiSS-1 proteins. Sequence analysis suggested that processing of the rat and mouse KiSS-1 proteins produces 52-amino-acid peptides, each with an amidated carboxyl terminal and with a single possible disulfide bond, corresponding to rat and mouse metastins. The carboxyl-terminal sequence of metastin, known to be essential for functional receptor interaction, was found to be highly conserved among humans and rodents. Real-time PCR analysis indicated that rat KiSS-1 mRNA showed the highest expression level in the cecum and colon. Since KiSS-1 mRNA and metastin are known to be abundant in human placenta, we further studied the localization of KiSS-1 and OT7T175 mRNAs in rat placenta by in situ hybridization. KiSS-1 and OT7T175 mRNAs were specifically detected in trophoblast giant cells at embryonic day 12.5, and the transcripts in the cells gradually decreased during placental maturation. These results suggest that metastin/OT7T175 signaling may participate in implantation of the mammalian embryo, placenta formation, and maintenance of pregnancy.