Chronic Peripheral Administration of Kappa-Opioid Receptor Antagonist
Advances Puberty Onset Associated with Acceleration of Pulsatile Luteinizing Hormone
Secretion in Female Rats |
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Authors: | Tatsuo NAKAHARA Yoshihisa UENOYAMA Akira IWASE Shinya OISHI Sho NAKAMURA Shiori MINABE Youki WATANABE Chikaya DEURA Taro NOGUCHI Nobutaka FUJII Fumitaka KIKKAWA Kei-ichiro MAEDA Hiroko TSUKAMURA |
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Institution: | 1)Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan;2)Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan;3)Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan;4)Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan |
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Abstract: | Puberty in mammals is timed by an increase in gonadotropin-releasing hormone (GnRH)
secretion. Previous studies have shown involvement of the two neuropeptides,
kisspeptin and neurokinin B (NKB), in controlling puberty onset. Little is known
about the role of the other key neuropeptide, dynorphin, in controlling puberty
onset, although these three neuropeptides colocalize in the arcuate kisspeptin
neurons. The arcuate kisspeptin neuron, which is also referred to as the KNDy neuron,
has recently been considered to play a role as an intrinsic source of the GnRH pulse
generator. The present study aimed to determine if attenuation of inhibitory
dynorphin-kappa-opioid receptor (KOR) signaling triggers the initiation of puberty in
normal developing female rats. The present study also determined if stimulatory
NKB-neurokinin 3 receptor (NK3R) signaling advances puberty onset. Female
Wistar-Imamichi rats were weaned and intraperitoneally implanted with osmotic
minipumps filled with nor-binaltorphimine (nor-BNI), a KOR antagonist, or senktide, a
NK3R agonist, at 20 days of age. Fourteen days of intraperitoneal infusion of nor-BNI
or senktide advanced puberty onset, manifested as vaginal opening and the first
vaginal estrus in female rats. Frequent blood sampling showed that nor-BNI
significantly increased luteinizing hormone (LH) pulse frequency at 29 days of age
compared with vehicle-treated controls. Senktide tended to increase this frequency,
but its effect was not statistically significant. The present results suggest that
the inhibitory input of dynorphin-KOR signaling plays a role in the prepubertal
restraint of GnRH/LH secretion in normal developing female rats and that attenuation
of dynorphin-KOR signaling and increase in NKB-NK3R signaling trigger the onset of
puberty in female rats. |
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Keywords: | GPR54 Metastin Sexual maturation |
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