Characterizing the influence of endogenous and exogenous sex steroid hormones in the stress response

表征内源性和外源性类固醇激素对应激反应的影响

• 批准号: RGPIN-2022-04896
• 负责人: McQuaid, Robyn
• 金额: $ 1.89万
• 依托单位: Carleton University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=761436
• 关键词: Characterizing; influence; endogenous; exogenous; sex

Sex hormones, such as estrogen, progesterone and testosterone have widespread influences on cognition, affective states, and stress reactivity. Indeed, fluctuations of sex hormones across the menstrual cycle correspond to altered brain activity and connectivity, alterations in stress hormones, such as cortisol, and pro-inflammatory cytokines (i.e., signaling molecules released by immune cells). Although there has been a shift in the past 10 years to include females in biological research, sex is most often not the focus of the investigation. As a result, significant gaps remain in our understanding as to how alterations in sex hormones, for example through the menstrual cycle or use of hormonal contraceptives, affects biological stress responses in females. With over 100 million women worldwide using hormone contraceptives there is a pressing need for the systematic examination of the how alterations of sex hormones impact female biology, as these may have significant consequences on cognition, behaviour and well-being. Therefore, the overarching objective of this program of research is to examine the role of sex hormones in biological responses to stressors and the long-term implications of disrupting sex hormones, through hormonal contraceptives. First, we will examine whether sex hormones account for sex differences seen between males and females in response to an acute social stressor in the laboratory. We will further assess how biological responses (e.g., cortisol and cytokine levels), to this laboratory stressor will differ according to menstrual cycle phase, and hormonal contraceptive use. We will similarly explore how sex hormones and hormonal contraceptives map onto gene expression, through a process called epigenetics. Moreover, a 2-year prospective study will allow us to assess the long-term associations of sex hormones, hormonal contraceptives and epigenetic patterns with later cortisol and inflammatory profiles. The current program of research will help reveal the short- and long-term biological implications of sex hormones among young females. Moreover, this research will provide novel insights into the targets of sex hormones by identifying top sites marked by epigenetic changes among naturally cycling females and those using hormonal contraceptives. Importantly, this research will tease-apart the biological consequences of estrogens versus progestin-only hormonal contraceptives. These findings could potentially inform policies regarding recommendations for specific hormonal contraceptives, which could directly impact behaviours, allowing females to make evidence-based decisions as to if, and what type of hormonal contraceptive is best for them.

性激素，如雌激素、孕激素和睾酮对认知、情感状态和应激反应有广泛的影响。事实上，性激素在月经周期中的波动对应于大脑活动和连接的改变、应激激素（如皮质醇）和促炎细胞因子（即，由免疫细胞释放的信号分子）。虽然在过去10年中出现了将女性纳入生物学研究的转变，但性往往不是调查的重点。因此，我们对性激素的变化，例如月经周期或使用激素避孕药，如何影响女性的生物应激反应的理解仍然存在重大差距。全世界有1亿多妇女使用激素避孕药，迫切需要系统地检查性激素的变化如何影响女性生物学，因为这些变化可能对认知，行为和福祉产生重大影响。因此，这项研究计划的总体目标是研究性激素在对压力源的生物反应中的作用，以及通过激素避孕药破坏性激素的长期影响。首先，我们将在实验室中研究性激素是否能解释男性和女性在应对急性社会压力时的性别差异。我们将进一步评估生物反应（例如，皮质醇和细胞因子水平），对这个实验室的压力将根据月经周期阶段和激素避孕药的使用而不同。我们将同样探索性激素和激素避孕药如何映射到基因表达，通过一个过程称为表观遗传学。此外，一项为期2年的前瞻性研究将使我们能够评估性激素、激素避孕药和表观遗传模式与后来的皮质醇和炎症特征的长期关联。目前的研究计划将有助于揭示性激素在年轻女性中的短期和长期生物学意义。此外，这项研究将通过确定自然循环女性和使用激素避孕药的女性中表观遗传变化的最高位点，为性激素的靶点提供新的见解。重要的是，这项研究将梳理除了雌激素与孕激素的激素避孕药的生物学后果。这些发现可能会为有关特定激素避孕药建议的政策提供信息，这可能会直接影响行为，使女性能够做出基于证据的决定，以及哪种激素避孕药最适合她们。