Central Administration of Neurokinin B Activates Kisspeptin/NKB Neurons in the Arcuate Nucleus and Stimulates Luteinizing Hormone Secretion in Ewes During the Non-Breeding Season

  • SAKAMOTO Kohei
    Laboratory of Veterinary Ethology, The University of Tokyo, Tokyo 113-8657, Japan Laboratory of Neurobiology, National Institute of Agrobiological Sciences, Ibaraki 305-0901, Japan
  • MURATA Ken
    Laboratory of Veterinary Ethology, The University of Tokyo, Tokyo 113-8657, Japan Laboratory of Neurobiology, National Institute of Agrobiological Sciences, Ibaraki 305-0901, Japan
  • WAKABAYASHI Yoshihiro
    Laboratory of Neurobiology, National Institute of Agrobiological Sciences, Ibaraki 305-0901, Japan
  • YAYOU Ken-ichi
    Laboratory of Neurobiology, National Institute of Agrobiological Sciences, Ibaraki 305-0901, Japan
  • OHKURA Satoshi
    Laboratory of Animal Production Science, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
  • TAKEUCHI Yukari
    Laboratory of Veterinary Ethology, The University of Tokyo, Tokyo 113-8657, Japan
  • MORI Yuji
    Laboratory of Veterinary Ethology, The University of Tokyo, Tokyo 113-8657, Japan
  • OKAMURA Hiroaki
    Laboratory of Neurobiology, National Institute of Agrobiological Sciences, Ibaraki 305-0901, Japan

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Abstract

Human genetic studies have suggested that kisspeptin and neurokinin B (NKB) play pivotal roles in the control of gonadotropin-releasing hormone (GnRH) secretion. However, the role of NKB in this context is less clear compared with that of kisspeptin. In the present study, we investigated the ratio of colocalization of kisspeptin and NKB in neurons in the arcuate nucleus (ARC), the effects of intracerebroventricular infusion of NKB on luteinizing hormone (LH) secretion and whether the treatment activates ARC kisspeptin/NKB neurons in seasonally anestrous ewes. Double-labeling immunohistochemistry revealed that the majority of kisspeptin neurons coexpressed NKB in the ARC. Infusion of NKB for 2 h into the lateral ventricle elicited a discharge of LH, which resulted in significant increases in LH concentrations between 20 and 50 min after the start of infusion compared with a saline-infused control. Animals were sacrificed immediately after the end of infusion, and Fos expression in ARC kisspeptin neurons was immunohistochemically examined. The NKB treatment activated kisspeptin neurons throughout the ARC, and approximately 70% of kisspeptin neurons expressed Fos immunoreactivity at the caudal portion of the nucleus. The present study demonstrated that a central infusion of NKB elicited a discharge of LH, which was associated with the activation of a large population of ARC kisspeptin/NKB neurons in seasonally anestrous ewes. The results suggest that NKB plays a stimulatory role in the control of pulsatile GnRH secretion and that the population of ARC kisspeptin/NKB neurons is one of sites of the NKB action in sheep.

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