Peripheral administration of metastin induces marked gonadotropin release and ovulation in the rat.
Metastin is a novel peptide that has been isolated from the human placenta as the cognate ligand of the G-protein-coupled receptor OT7T175 (or GPR54). However, its physiological functions have not yet been fully investigated. In the present study, we show that subcutaneous administration of metastin increased the plasma levels of gonadotropins (follicle-stimulating hormone and luteinizing hormone) and induced ovulation in prepubertal female rats that had been pretreated with pregnant mare serum gonadotropin to induce follicle maturation. Furthermore, metastin administration drastically increased the plasma levels of gonadotropins in male rats. This action was abolished by pretreatment with a GnRH antagonist, and was accompanied by induction of c-Fos immunoreactivity in GnRH neurons. These results suggest that s.c. administered metastin induces the release of gonadotropin via activation of the hypothalamic GnRH neurons.
Matsui
Hisanori
H
Discovery Research Laboratories, Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., Wadai 10, Tsukuba, Ibaraki 300-4293, Japan.
Takatsu
Yoshihiro
Y
Kumano
Satoshi
S
Matsumoto
Hirokazu
H
Ohtaki
Tetsuya
T
D000818:Animals; D006062:Gonadotropins / Q000378:metabolism*; D008297:Male; D010060:Ovulation / Q000187:drug effects*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D006062:Gonadotropins; D016760:Proto-Oncogene Proteins c-fos