TOBACCO SMOKE EXPOSURE AND HORMONAL CHANGES IN WOMEN

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本研究的目的是探讨吸烟与遗传易感性对绝经前妇女激素水平变化的关系和影响。我们希望阐明荷尔蒙紊乱中的基因-环境相互作用，以确定存在的不良暴露，并引入预防措施，以消除对母亲和未来婴儿的风险。 二手烟是一种动态的、复杂的混合物，由数千种化合物组成，包括致癌物质和刺激物，以及被怀疑会对生殖系统造成损害、增加怀孕损失的可能性并导致婴儿低出生体重的化合物。一些研究表明，吸烟可能会改变激素水平，进而可能对炎症、癌症、生育和怀孕等激素依赖型疾病产生影响。烟雾暴露引起的激素功能变化会显著影响女性的生育能力，她们的月经周期更短，更年期更早，患激素依赖型癌症的风险更高。吸烟是如何导致这些荷尔蒙变化的尚不清楚。在这项研究中，我们将尝试回答以下两个问题：吸烟者和不吸烟者的类固醇激素水平是否存在差异？与突变基因类型相比，在正常基因类型的女性中，吸烟与激素水平之间的关联是否存在显著差异？因此，我们将研究这些与吸烟相关的激素浓度变化是否特定于遗传上更容易发生这些变化的女性。为此，我们将检查四个与类固醇激素代谢有关的基因，看看在这些特定基因发生突变的女性中，吸烟导致的激素浓度变化是否更深远。同位素稀释串联质谱仪(MS/MS)是一种为激素(或其他物质)的准确定量提供卓越专属性的技术。在这项研究中，我们将使用MS/MS准确地测量类固醇和甲状腺激素的浓度。这是首次研究暴露在香烟烟雾中的大量类固醇和甲状腺激素浓度的变化。据我们所知，还没有使用MS/MS技术对这些激素和香烟烟雾进行研究。 作为这项研究的结果，我们希望更多地了解香烟烟雾和遗传如何影响激素系统，特别是烟草烟雾对类固醇激素浓度变化的影响。如果我们发现这些基因与这一人群中任何一种荷尔蒙的特定变化有关的证据，这些发现将有助于我们了解这些基因在女性健康、不孕和癌症病因中所起的作用。这些荷尔蒙和遗传生物标志物可以作为疾病预防的早期预警。在以后的阶段，我们还希望研究吸烟对怀孕期间类固醇和甲状腺激素变化的影响。这项研究与FAMRI的目标直接相关，即了解香烟烟雾的生物医学影响。它具有成本效益，因为它使用GUMC的设施和服务，而无需外包，我们将能够在短时间内取得重要成果。这项研究只需要血样，但它使用了最新的技术来回答非常重要的问题。类固醇激素分析是在单个样本上进行的，因此减少了个体内的任何差异，并且只需少量的血液，我们就能够产生实质性的结果。一些研究探讨了吸烟与荷尔蒙浓度变化之间的关系。在这项研究中，我们将确定吸烟和参与类固醇激素生物合成和代谢的基因多态性是否与女性激素变化有关。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this project is to explore the relationship between, and effect of cigarette smoke and genetic predisposition on alterations in hormone levels in premenopausal women. We hope to elucidate the gene-environment interaction in hormonal disruption in order to identify existing adverse exposure, and introduce preventative measures to eliminate risks to mother and future baby. Second-hand smoke is a dynamic, complex mixture of thousands of compounds, including carcinogens and irritants, as well as compounds suspected to cause damage to the reproductive system, increase the likelihood of pregnancy loss and cause low birth weight in infants. A few studies indicate that cigarette smoke may alter hormone levels, which in turn could have an effect on hormone-dependent conditions such as inflammation, cancer, fertility and pregnancy. Changes in hormone function from smoke exposure can significantly impact a woman's ability to have children, their menstrual cycles are shorter, menopause is earlier and they have a higher risk of development of hormone-dependent cancers. How smoke exposure may cause these hormonal changes is not clear. In this study we will try and answer the following two questions: Is there a difference in the levels of steroid hormones between smokers and non-smokers? And is the association between cigarette smoke and hormone levels significantly different in women with normal gene types compared to mutant gene types? Therefore, we will examine if these cigarette smoke-related alterations in hormone concentrations are specific to women who are genetically more prone to these changes. For that purpose, we will examine four genes responsible for steroid hormone metabolism to see if the changes in hormone concentrations due to cigarette smoke are more profound in women who have mutations in these specific genes. Isotope-dilution tandem mass spectrometry (MS/MS) is technology that provides superior specificity for accurate quantification of hormones (or other substances). In this study, we will use MS/MS to accurately measure the concentrations of steroid and thyroid hormones. This is the first study to investigate changes in concentrations of a large number of steroid and thyroid hormones due to exposure to cigarette smoke. To our knowledge, no studies of these hormones and cigarette smoke have been conducted using MS/MS technology. As a result of this study, we expect to learn more about how cigarette smoke and genetics affect hormone systems, and in particular the effects of tobacco smoke on changes in steroid hormone concentrations. If we find evidence that these genes are associated with specific changes in any of the hormones in this population, the findings will help us understand the role these genes play in women's health, infertility and cancer etiology. These hormonal and genetic biomarkers can serve as an early warning for disease prevention. At a later stage, we hope to also examine tobacco smoke effects on steroid and thyroid hormone changes during pregnancy. This study is directly relevant to the goals of FAMRI, to understand the biomedical effects of cigarette smoke. It is cost-effective because it uses GUMC facilities and services without having to contract out, and we will be able to have important results within a short period of time. The study only requires a blood sample, yet it uses the most recent technology to answer very important questions. The steroid hormone analysis is performed on a single sample thus reducing any intra-individual variations and with a small amount of blood we will be able to produce substantial results. Several studies have examined the relationship between cigarette smoke and changes in hormone concentrations. In this study we will determine whether tobacco smoke and polymorphisms in genes involved in steroid hormone biosynthesis and metabolism are associated with hormone changes in women.