Effects of Light and Melatonin on Contractions in Pregnant Women

 描述（由申请人提供）：褪黑激素被昵称为“德古拉”激素，因为它通常在夜间分泌，并且这种分泌受到眼部光照的抑制。在足月妊娠中，分娩通常在夜间开始。妊娠子宫上有褪黑激素受体，在分娩期间被激活。我们建议使用这三个生理事实为基础，测试一个潜在的非侵入性干预，改变子宫收缩在晚期妊娠妇女：内源性褪黑激素分泌的光抑制。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。受非可见光暴露影响的生理功能包括激素浓度（例如，褪黑激素抑制）、昼夜节律相位和振幅、主观警觉性和瞳孔对光反射。褪黑激素对光的反应是季节性繁殖动物监测日照长度的方式。光诱导的褪黑激素和其他生理功能的抑制是波长依赖性的;这些非可见光响应对蓝色/绿色波长最敏感，对红色波长不太敏感。在我们最近对6名晚期孕妇进行的研究中，包括夜间眼部光照，暴露于蓝光/绿色光的妇女的褪黑激素浓度较低，子宫收缩也比暴露于红光的妇女少。褪黑激素的分泌总量与光暴露期间的收缩总数之间存在显著的正相关（R2 = 0.87）。这些令人兴奋的初步数据使这项研究提案成为NIH R21机制的理想选择，因为（i）它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可用数据有限;和（iii）这些研究可能导致更好地理解生理学和开发新技术，方法，以及可能对生物医学和临床研究和实践领域产生重大影响的应用。我们已经证明了我们有能力进行研究的各个方面，包括招募，门诊和住院监测，实验光照和褪黑激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。如果眼部光暴露能够抑制早产（其发生在超过12%的所有妊娠中），则其将是一种廉价、非侵入性、易于使用且副作用最小的方法。同样重要的是，除了催产素之外，使用药物褪黑激素可能有利于引产，包括允许降低催产素的浓度。

 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.