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 |
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| Authors: | Tomomi TANAKA Satoshi OHKURA Yoshihiro WAKABAYASHI Takenobu KUROIWA Kiyosuke NAGAI Natsumi ENDO Akira TANAKA Hisanori MATSUI Masami KUSAKA Hiroaki OKAMURA |
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| Institution: | 1)Laboratory of Veterinary Reproduction, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan;2)Laboratory of Animal Production Science, Nagoya University, Nagoya 464-8601, Japan;3)Laboratory of Neurobiology, National Institute of Agrobiological Sciences, Ibaraki 305-8602, Japan;4)Takeda Pharmaceutical Company Limited, Kanagawa 251-0012, 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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| Keywords: | Estradiol Goats Kisspeptin analog LH surge |
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