Kanai Nahoko, Endo Natsumi, Ohkura Satoshi, Wakabayashi Yoshihiro, Matsui Hisanori, Matsumoto Hirokazu, Ishikawa Kaori, Tanaka Akira, Watanabe Tatsuya, Okamura Hiroaki, Tanaka Tomomi
Laboratory of Veterinary Reproduction, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.
Laboratory of Animal Production Science, Nagoya University, Nagoya 464-8601, Japan.
J Reprod Dev. 2017 Jun 21;63(3):305-310. doi: 10.1262/jrd.2016-184. Epub 2017 Mar 24.
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 F 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.
本研究旨在评估低剂量TAK - 683给药后山羊体内的激素反应及其与TAK - 683血药浓度的关联,该低剂量先前已被确定为去卵巢山羊促黄体生成素(LH)刺激的最小有效剂量。在实验1中,5μg TAK - 683处理对去卵巢柴山羊(n = 4)的LH分泌无显著刺激作用。在实验2中,处于发情周期的山羊接受前列腺素F和孕酮释放型皮下埋植剂(CIDR)处理以诱导卵泡期,然后在取出CIDR后12小时,静脉注射5μg TAK - 683(n = 4,IV组)或皮下注射(n = 3,SC组),或静脉注射赋形剂(n = 4,对照组)。在 - 2至6小时期间每10分钟、6至24小时期间每2小时、24至48小时期间每6小时采集血样。每天评估卵巢超声图像以确认处理后的排卵情况。IV组(峰值时间:4.2±0.6小时,峰值浓度:73.3±27.5 ng/ml)和SC组(峰值时间:4.6±0.4小时,峰值浓度:62.6±23.2 ng/ml)的所有动物在注射后立即观察到LH呈激增样释放,但对照组未观察到。IV组和SC组的所有动物在TAK - 683注射后3天内检测到排卵,且IV组从TAK - 683给药到排卵的间隔时间显著短于对照组(P < 0.05)。排卵后,IV组和SC组在黄体直径和血孕酮水平方面未观察到显著变化。目前的研究结果表明,一种或多种卵巢因子参与TAK - 683诱导的LH激增从而导致山羊排卵是必不可少的。