MRC Centre for Reproductive Health, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Warwick Medical School, Coventry, United Kingdom.
J Clin Endocrinol Metab. 2018 Jan 1;103(1):95-104. doi: 10.1210/jc.2017-01306.
Neurokinin B (NKB) is obligate for human puberty, but its role in adult female gonadotropin secretion and ovarian follicle growth is unknown.
To investigate antagonism of NKB on pulsatile gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion and ovarian follicle development in healthy women.
Open investigation of the effects of a neurokinin-3 receptor (NK3R) antagonist (NK3Ra) vs a no-treatment control cycle.
Clinical research facility.
Healthy women with regular menses (n = 13).
INTERVENTION(S): NK3Ra MLE4901 40 mg taken orally twice daily from cycle day 5 to 6 for 7 days.
MAIN OUTCOME MEASURE(S): LH secretion, ovarian follicle growth, and timing of ovulation.
NK3Ra administration reduced basal LH secretion without a change in pulse frequency and delayed the LH surge by 7 days, the duration of treatment [mean cycle day ± standard error of the mean (SEM), 22 ± 1 days vs 15 ± 1 days in control cycles; P = 0.0006]. Follicle growth (mean diameter at the end of administration of NK3Ra administration ± SEM, 9.3 ± 0.4 mm vs 15.1 ± 0.9 mm in control cycles; P < 0.0001) and rising estradiol concentrations (mean ± SEM, 166 ± 29 pmol/L vs 446 ± 86 pmol/L in control cycles; P < 0.0001) were prevented. After treatment, follicle development resumed and normal preovulatory follicle diameter and estradiol concentrations were demonstrated. Postovulatory progesterone rise was similarly delayed (peak cycle day, 30 ± 2 vs 22 ± 1; P = 0.002) and cycle length was prolonged (35 ± 1 days vs 29 ± 1 days in control cycles; P = 0.0003) but luteal progesterone excretion was unaffected by the NK3Ra (LH surge day +7 mean urinary progesterone levels ± SEM, 58 ± 10 pmol/mol vs 48±7 pmol/mol creatinine in control cycles; nonsignificant).
These data demonstrate the involvement of NKB-NK3R signaling in the physiological regulation of GnRH/LH secretion, determining normal follicle development in women.
神经激肽 B（NKB）是人类青春期所必需的，但它在成年女性促性腺激素分泌和卵巢卵泡生长中的作用尚不清楚。
研究神经激肽-3 受体（NK3R）拮抗剂（NK3Ra）对健康女性脉冲式促性腺激素释放激素（GnRH）和黄体生成素（LH）分泌及卵巢卵泡发育的抑制作用。
对 NK3Ra 与无治疗对照周期的影响进行开放性研究。
临床研究设施。
月经规律的健康女性（n=13）。
NK3Ra MLE4901 40mg，每天口服 2 次，从月经周期第 5 天至第 6 天连续服用 7 天。
LH 分泌、卵巢卵泡生长和排卵时间。
NK3Ra 给药降低了基础 LH 分泌，但脉冲频率没有变化，并将 LH 激增延迟了 7 天，治疗持续时间[平均月经周期日±均数标准差（SEM），22±1 天 vs 对照组 15±1 天；P=0.0006]。卵泡生长（NK3Ra 给药结束时的平均直径±SEM，9.3±0.4mm vs 对照组 15.1±0.9mm；P<0.0001）和雌二醇浓度升高（平均±SEM，166±29pmol/L vs 对照组 446±86pmol/L；P<0.0001）被阻止。治疗后，卵泡发育恢复，表现出正常的排卵前卵泡直径和雌二醇浓度。排卵后孕酮升高也同样延迟（峰值周期日，30±2 vs 22±1；P=0.002），周期延长（35±1 天 vs 对照组 29±1 天；P=0.0003），但 NK3Ra 对黄体孕酮排泄无影响（LH 激增日后 7 天平均尿孕酮水平±SEM，58±10pmol/mol vs 对照组 48±7pmol/mol 肌酐；无显著差异）。
这些数据表明，NKB-NK3R 信号参与了 GnRH/LH 分泌的生理调节，决定了女性正常的卵泡发育。
