An administration of TAK-683 at a minimally effective dose for luteinizing hormone stimulation under the absence of the ovary induces luteinizing hormone surge in ovary-intact goats

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  • KANAI Nahoko
    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
  • 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
  • MATSUI Hisanori
    Takeda Pharmaceutical Company Limited, Kanagawa 251-0012, Japan
  • MATSUMOTO Hirokazu
    Takeda Pharmaceutical Company Limited, Kanagawa 251-0012, Japan
  • ISHIKAWA Kaori
    Takeda Pharmaceutical Company Limited, Kanagawa 251-0012, Japan
  • TANAKA Akira
    Takeda Pharmaceutical Company Limited, Kanagawa 251-0012, Japan
  • WATANABE Tatsuya
    Takeda Pharmaceutical Company Limited, Kanagawa 251-0012, Japan
  • OKAMURA Hiroaki
    Laboratory of Neurobiology, National Institute of Agrobiological Sciences, Ibaraki 305-8602, Japan
  • TANAKA Tomomi
    Laboratory of Veterinary Reproduction, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan

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Abstract

<p> The present study aimed to evaluate hormonal responses and their association with the TAK-683 blood concentrations in goats administered TAK-683 at a low dose, which had been previously determined as the minimally effective dose for luteinizing hormone (LH) stimulation in ovariectomized goats. In Experiment 1, 5 µg of TAK-683 treatment had no significant stimulatory effect on LH secretion in ovariectomized Shiba goats (n = 4). In Experiment 2, cycling goats received the treatment of prostaglandin F2α and progesterone-releasing controlled internal drug releasing (CIDR) to induce the follicular phase, then they were treated with 5 µg of TAK-683 (hour 0) intravenously (n = 4, IV) or subcutaneously (n = 3, SC) or with vehicle intravenously (n = 4, control) at 12 h after CIDR removal. Blood samples were collected at 10-min (–2–6 h), 2-h (6–24 h), or 6-h (24–48 h) intervals. Ovarian ultrasonographic images were assessed daily to confirm ovulation after the treatment. A surge-like release of LH was immediately observed after injection in all animals in the IV (peak time: 4.2 ± 0.6 h, peak concentration: 73.3 ± 27.5 ng/ml) and SC (peak time: 4.6 ± 0.4 h, peak concentration: 62.6 ± 23.2 ng/ml) groups, but not in the control group. Ovulation was detected within 3 days after TAK-683 injection in all animals in the IV and SC groups, and the interval period from TAK-683 administration to ovulation in the IV group was significantly (P < 0.05) shorter than that of the control group. No significant changes were observed between the IV and SC groups in terms of luteal diameter and blood progesterone levels after ovulation. The present findings suggest that the involvement of one or more ovarian factor(s) is indispensable for a TAK-683-induced LH surge leading to ovulation in goats.</p>

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