Effects of Light and Melatonin on Contractions in Pregnant Women

 描述(申请人提供)：褪黑激素被戏称为“德古拉”荷尔蒙，因为它通常在晚上分泌，这种分泌被眼睛光线照射所抑制。在足月妊娠中，分娩通常在晚上开始。怀孕的子宫上有褪黑素受体，在分娩过程中足月时被激活。我们建议使用这三个生理事实作为测试一种潜在的非侵入性干预措施来改变晚期妊娠妇女的子宫收缩：光抑制内源性褪黑素分泌。哺乳动物的眼睛通过视觉和非视觉细胞和途径处理光暴露。非视觉光暴露影响的生理功能包括激素浓度(例如，褪黑激素抑制)、昼夜节律相位和幅度、主观警觉性和瞳孔光反射。褪黑激素对光的反应是季节性繁殖的动物监测日长的方式。光诱导的褪黑素抑制和其他生理功能依赖于波长；这些非视觉光反应对蓝/绿波长最敏感，对红色波长更不敏感。在我们最近对六名晚期孕妇的研究中，包括夜间眼光暴露，暴露在蓝/绿光下的妇女比暴露在红光下的妇女褪黑素浓度更低，子宫收缩也更少。褪黑素总分泌量与总收缩次数呈显著正相关(R2=0.87)。这些令人兴奋的初步数据使这项研究建议成为NIH R21机制的理想选择，因为(I)这是一个新的探索性和发展性研究项目；(Ii)目前关于这一主题的数据有限；以及(Iii)这些研究可能导致在更好地理解生理学和开发可能对生物医学和临床研究和实践领域产生重大影响的新技术、方法和应用方面的突破。我们已经证明了我们有能力进行研究的所有方面，包括招募、门诊和住院监测、实验性光暴露以及褪黑素浓度和子宫收缩的生理数据收集。这些发现对产科实践的影响可能是戏剧性的。如果眼光暴露能够抑制早产(在所有怀孕中发生的早产超过12%)，这将是一种廉价、非侵入性、易于使用、副作用最小的方法。同样重要的是，除了催产素之外，使用药物褪黑素可能对引产有利，包括允许降低给药的催产素浓度。

 DESCRIPTION (provided by applicant): Melatonin is nicknamed the "Dracula" hormone because it is usually secreted at night and this secretion is suppressed by ocular light exposure. In term pregnancies, labor is more often initiated at night. There are melatonin receptors on the pregnant uterus that are activated at term during labor. We propose to use these three physiological facts as the basis for testing a potential non-invasive intervention for altering uterine contractions in late-term pregnant women: photic suppression of endogenous melatonin secretion. The mammalian eye processes light exposure through visual and non-visual cells and pathways. Physiological functions affected by non-visual light exposure include hormone concentrations (e.g., melatonin suppression), circadian rhythm phase and amplitude, subjective alertness, and the pupillary light reflex. The melatonin response to light is how seasonally-reproductive animals monitor daylength. Light-induced suppression of melatonin and other physiological functions is wavelength dependent; these non-visual light responses are most sensitive to blue/green wavelengths and much less to red wavelengths. In our recent studies in six late-term pregnant women that included nighttime ocular light exposure, women who were exposed to blue/green light had lower concentrations of melatonin and fewer uterine contractions than those exposed to red light. There was a significant positive relationship (R2 = 0.87) between the total amount of melatonin secreted and the total number of contractions during the light exposure. These exciting preliminary data make this research proposal ideal for the NIH R21 mechanism in that (i) it is a new exploratory and developmental research project; (ii) currently available data on this topic are limited; and (iii) these studies may lead to a breakthrough in better understanding of physiology and development of novel techniques, methodologies, and applications that could have a major impact on a field of biomedical and clinical research and practice. We have demonstrated our ability to conduct all aspects of the study, including recruitment, outpatient and inpatient monitoring, experimental light exposure and physiological data collection of melatonin concentrations and uterine contractions. Ramifications of these findings for the practice of obstetrics could be dramatic. If ocular light exposure were able to suppress pre-term labor (which occurs in more than 12% of all pregnancies), it would be an inexpensive, non-obtrusive, easy- to-use method with minimal side effects. Of equal importance, the use of pharmaceutical melatonin in addition to oxytocin might be beneficial in inducing labor, including allowing reduction of the concentrations of oxytocin administered.