Kisspeptin neurons mediate reflex ovulation in the musk shrew (Suncus murinus)

• Published in: Proceedings of the National Academy of Sciences - PNAS 2011-10, Vol.108 (42), p.17527-17532
• Main Authors: Inoue, Naoko, Sasagawa, Karin, Ikai, Kotaro, Sasaki, Yuki, Tomikawa, Junko, Oishi, Shinya, Fujii, Nobutaka, Uenoyama, Yoshihisa, Ohmori, Yasushige, Yamamoto, Naoyuki, Hondo, Eiichi, Maeda, Kei-ichiro, Tsukamura, Hiroko
• Format: Article
• Language: English
• Subjects: agonists; Amino Acid Sequence; Amino acids; Animals; antagonists; Arcuate nucleus; Arcuate Nucleus of Hypothalamus - drug effects; Arcuate Nucleus of Hypothalamus - physiology; Base Sequence; Biological Sciences; Brain; c-Fos protein; Cells; Complementary DNA; Copulation - physiology; Corpus Luteum - physiology; DNA, Complementary - genetics; Estradiol; Estradiol - pharmacology; Estrogens; Feedback; Female; Gene Expression - drug effects; Gonadotropin-releasing hormone; Gonadotropin-Releasing Hormone - physiology; Hormonal regulation; Hybridization; in situ hybridization; Kiss1 protein; Kisspeptins - genetics; Kisspeptins - physiology; Male; Mating; Mating behavior; Messenger RNA; Molecular Sequence Data; mRNA; Neurons; Ovarian Follicle - physiology; Ovaries; Ovulation; Ovulation - genetics; Ovulation - physiology; Phylogeny; Preoptic area; Preoptic Area - drug effects; Preoptic Area - physiology; Proteins; Rats; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - physiology; Reflexes; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Sequence Homology, Amino Acid; Shrews; Shrews - physiology; Suncus; Suncus murinus; Tissue Distribution
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1113035108

The present study investigated whether kisspeptin–G protein-coupled receptor 54 (GPR54) signaling plays a role in mediating mating-induced ovulation in the musk shrew (Suncus murinus), a reflex ovulator. For this purpose, we cloned suncus Kiss1 and Gpr54 cDNA from the hypothalamus and found that suncus kisspeptin (sKp) consists of 29 amino acid residues (sKp-29). Injection of exogenous sKp-29 mimicked the mating stimulus to induce follicular maturation and ovulation. Administration of several kisspeptins and GPR54 agonists also induced presumed ovulation in a dose-dependent manner, and Gpr54 mRNA was distributed in the hypothalamus, showing that kisspeptins induce ovulation through binding to GPR54. The sKp-29–induced ovulation was blocked completely by pretreatment with a gonadotropin-releasing hormone (GnRH) antagonist, suggesting that kisspeptin activates GnRH neurons to induce ovulation in the musk shrew. In addition, in situ hybridization revealed that Kiss1-expressing cells are located in the medial preoptic area (POA) and arcuate nucleus in the musk shrew hypothalamus. The number of Kiss1-expressing cells in the POA or arcuate nucleus was up-regulated or down-regulated by estradiol, suggesting that kisspeptin neurons in these regions were the targets of the estrogen feedback action. Finally, mating stimulus largely induced c-Fos expression in Kiss1-positive cells in the POA, indicating that the mating stimulus activates POA kisspeptin neurons to induce ovulation. Taken together, these results indicate that kisspeptin–GPR54 signaling plays a role in the induction of ovulation in the musk shrew, a reflex ovulator, as it does in spontaneous ovulators.