Leibniz Institute for Farm Animal Biology, 18196 Dummerstorf, Germany.
Hum Reprod. 2013 Nov;28(11):3093-102. doi: 10.1093/humrep/det349. Epub 2013 Sep 5.
How does insulin-like factor 3 (INSL3) concentration in blood vary across the menstrual cycle in women?
INSL3 is secreted by the theca interna cells of growing antral follicles and is phasic in its expression.
The relaxin-like hormone INSL3 is known to be expressed in follicles of several mammal species, and was recently shown in cows to be specifically secreted into the bloodstream by growing antral follicles, corresponding to follicular waves. In males INSL3 is known to be acutely independent of the hormones of the hypothalamic-pituitary-gonadal axis, suggesting that in women INSL3 might be a novel biomarker for antral follicle recruitment and development.
STUDY DESIGN, SIZE, DURATION: Two cohorts of women were studied. First, 18 healthy women of reproductive age were followed longitudinally for one and a half cycles, with blood sampling and hormone measurement every 2-3 days. A second cohort comprised a cross-sectional study of 909 women attending an infertility clinic, with a single blood sample taken at entry, together with other clinical and hormonal parameters.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Blood samples from both retrospective cohorts were analyzed for INSL3 using a highly sensitive time-resolved fluorescent immunoassay, and data were analyzed in comparison with other clinical and hormonal parameters.
For young healthy women of reproductive age, we showed a phasic expression of INSL3 corresponding to antral follicle growth in both the follicular and luteal phases of the cycle, which was significantly (P < 0.05) elevated compared with that during menses. For women attending an infertility clinic, those with diagnosed polycystic ovarian syndrome indicated significantly (P < 0.0005) greater circulating INSL3 levels and those with low ovarian reserve showed significantly (P < 0.002) decreased INSL3 values.
LIMITATIONS, REASONS FOR CAUTION: These were retrospective studies and the results were obtained from natural cycles only, with their inherent variability.
We show for the first time that INSL3 in women does vary across the menstrual cycle, and appears to reflect the number of growing antral follicles recruited within both follicular and luteal phases.
STUDY FUNDING/COMPETING INTEREST(S): The present retrospective study was largely supported by departmental funds. There were no competing interests.
女性的血液中胰岛素样因子 3（INSL3）浓度在月经周期中如何变化？
INSL3 由生长的窦卵泡的内膜细胞分泌，其表达呈阶段性。
众所周知，松弛素样激素 INSL3 存在于几种哺乳动物的卵泡中，最近在奶牛中发现它专门由生长的窦卵泡分泌到血液中，与卵泡波相对应。在男性中，INSL3 已知与下丘脑-垂体-性腺轴的激素急性无关，这表明在女性中，INSL3 可能是窦卵泡募集和发育的新的生物标志物。
研究设计、大小和持续时间：对两个队列的女性进行了研究。首先，对 18 名处于生育年龄的健康女性进行了为期一个半周期的纵向随访，每 2-3 天进行一次血液采样和激素测量。第二个队列由在不孕诊所就诊的 909 名女性的横断面研究组成，在就诊时采集了一份血液样本，同时还采集了其他临床和激素参数。
参与者/材料、设置、方法：使用高度敏感的时间分辨荧光免疫分析法分析两个回顾性队列的血液样本中的 INSL3，并将数据与其他临床和激素参数进行比较。
对于处于生育年龄的年轻健康女性，我们显示 INSL3 的表达呈阶段性，与周期中的卵泡期和黄体期的窦卵泡生长相对应，与月经期间相比明显升高（P <0.05）。对于在不孕诊所就诊的女性，诊断为多囊卵巢综合征的女性表明循环 INSL3 水平显著升高（P <0.0005），而卵巢储备功能低下的女性表明循环 INSL3 值显著降低（P <0.002）。
局限性、谨慎的原因：这些都是回顾性研究，结果仅来自自然周期，具有内在的可变性。
我们首次表明，女性的 INSL3 在月经周期中确实会发生变化，并且似乎反映了在卵泡期和黄体期募集的生长窦卵泡的数量。
研究资金/利益冲突：本回顾性研究主要由部门资金支持。没有竞争利益。
