Differential Effects of Continuous Exposure to the Investigational Metastin/Kisspeptin Analog TAK-683 on Pulsatile and Surge Mode Secretion of Luteinizing Hormone in Ovariectomized Goats

  • TANAKA Tomomi
    Laboratory of Veterinary Reproduction, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan
  • OHKURA Satoshi
    Laboratory of Animal Production Science, Nagoya University, Nagoya 464-8601, Japan
  • WAKABAYASHI Yoshihiro
    Laboratory of Neurobiology, National Institute of Agrobiological Sciences, Ibaraki 305-8602, Japan
  • KUROIWA Takenobu
    Laboratory of Veterinary Reproduction, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan
  • NAGAI Kiyosuke
    Laboratory of Veterinary Reproduction, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan
  • ENDO Natsumi
    Laboratory of Veterinary Reproduction, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan
  • TANAKA Akira
    Takeda Pharmaceutical Company Limited, Kanagawa 251-0012, Japan
  • MATSUI Hisanori
    Takeda Pharmaceutical Company Limited, Kanagawa 251-0012, Japan
  • KUSAKA Masami
    Takeda Pharmaceutical Company Limited, Kanagawa 251-0012, Japan
  • OKAMURA Hiroaki
    Laboratory of Neurobiology, National Institute of Agrobiological Sciences, Ibaraki 305-8602, Japan

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Abstract

The aim of the present study was to determine if the estradiol-induced luteinizing hormone (LH) surge is influenced by the constant exposure to TAK-683, an investigational metastin/kisspeptin analog, that had been established to depress the pulsatile gonadotropin-releasing hormone (GnRH) and LH secretion in goats. Ovariectomized goats subcutaneously received TAK-683 (TAK-683 group, n=6) or vehicle (control group, n=6) constantly via subcutaneous implantation of an osmotic pump. Five days after the start of the treatment, estradiol was infused intravenously in both groups to evaluate the effects on the LH surge. Blood samples were collected at 6-min intervals for 4 h prior to the initiation of either the TAK-683 treatment or the estradiol infusion, to determine the profiles of pulsatile LH secretion. They were also collected at 2-h intervals from –4 h to 32 h after the start of estradiol infusion for analysis of LH surges. The frequency and mean concentrations of LH pulses in the TAK-683 group were remarkably suppressed 5 days after the start of TAK-683 treatment compared with those of the control group (P<0.05). On the other hand, a clear LH surge was observed in all animals of both groups. There were no significant differences in the LH concentrations for surge peak and the peak time of the LH surge between the TAK-683 and control groups. These findings suggest that the effects of continuous exposure to kisspeptin or its analog on the mechanism(s) that regulates the pulsatile and surge mode secretion of GnRH/LH are different in goats.

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