Effects of menstrual cycles on the human circadian clock

在发情周期的血液雌二醇水平高的那一天，雌性仓鼠开始它们的夜间活动阶段更早，在整个发情周期中自发活动节律的这种变化可能是由雌激素和孕激素对昼夜节律的直接影响引起的。然而，尚未报道人类女性在昼夜节律中显示月经变化。我们研究了6名健康女性和6名经前综合征（PMS）患者的月经周期对昼夜节律的影响。我们测量了手腕活动和温度的昼夜节律以及卵泡期（FP）和黄体期（LP）的血浆褪黑激素浓度。在健康女性和经前综合征女性中，睡眠和体温的昼夜节律没有月经变化。然而，发病的夜间褪黑激素上升延迟约1小时，在LP的PMS妇女，虽然没有相移观察到健康妇女。因此，在大鼠中观察到的昼夜节律的发情变化可能在人类女性中受到抑制。我们观察到一名PMS女性，她在月经周期的睡眠、温度和褪黑激素节律中表现出交替的相移：卵泡期的渐进性相位提前和黄体期的相位延迟，其方式类似于仓鼠。我们推测该受试者可能参与了抑制机制的紊乱。为了阐明这种疾病的病因，我们检测了17β-雌二醇（E2）对生物钟所在的视交叉上核（SCN）中神经元间缝隙连接基因连接蛋白-32 mRNA表达的影响。E2使SCN中连接蛋白32 mRNA表达增加。SCN神经元间通讯功能障碍可能参与了本病的发病机制，因为我们已经证明大鼠SCN中存在缝隙连接偶联神经元。

On the day of the estrous cycle during which blood levels of estradiol are high, female hamsters start their nocturnal activity phase earlier, This change in the locomotor activity rhythm throughout the estrous cycle may be caused by a direct effect of estrogen and progesterone on the circadian clock. However, it has not been reported that human females show a menstrual variation in circadian rhythms. We examined the effects of the menstrual cycle on circadian rhythms in 6 healthy women and 6 women with premenstrual syndrome (PMS). We measured circadian rhythms of wrist activity and temperature as well as plasma concentration of melatonin in the follicular phase (FP) and luteal phase (LP). In healthy women and PMS women, there was no menstrual change in circadian rhythms in sleep and temperature. However, the onset of the nocturnal melatonin rise was delayed by about 1 hr in the LP in PMS women although no phase shift was observed in healthy women. Therefore, estrous changes in circadian rhythm as observed in rats may be inhibited in human females. We observed a PMS woman who showed alternative phase shifts in the sleep, temperature and melatonin rhythms in the menstrual cycle : progressive phase advances in the follicular phase and phase delays in the luteal phase in a way similar to hamsters. We speculated that disturbance of the inhibition mechanism might be involved in this subject. To clarify the etiology of this disease, we examined the effects of 17β-estradiol (E2) on the expression of an interneuronal gap junction gene connexin-32 mRNA in the suprachiasmatic nucleus (SCN), the site of the circadian clock. E2 increased connexin-32 mRNA in the SCN. Dysfunction of interneuronal communication in the SCN bay be involved in the mechanism of this disease since we have shown that gap junction couple neurons in the rat SCN.