Université Bordeaux, INRAE, UMR1286, Nutrineuro, 33076 Bordeaux, France.
Int J Mol Sci. 2021 Mar 19;22(6):3139. doi: 10.3390/ijms22063139.
Chronic stress is encountered in our everyday life and is thought to contribute to a number of diseases. Many of these stress-related disorders display a sex bias. Because glucocorticoid hormones are the main biological mediator of chronic stress, researchers have been interested in understanding the sexual dimorphism in glucocorticoid stress response to better explain the sex bias in stress-related diseases. Although not yet demonstrated for glucocorticoid regulation, sex chromosomes do influence sex-specific biology as soon as conception. Then a transient rise in testosterone start to shape the male brain during the prenatal period differently to the female brain. These organizational effects are completed just before puberty. The cerebral regions implicated in glucocorticoid regulation at rest and after stress are thereby impacted in a sex-specific manner. After puberty, the high levels of all gonadal hormones will interact with glucocorticoid hormones in specific crosstalk through their respective nuclear receptors. In addition, stress occurring early in life, in particular during the prenatal period and in adolescence will prime in the long-term glucocorticoid stress response through epigenetic mechanisms, again in a sex-specific manner. Altogether, various molecular mechanisms explain sex-specific glucocorticoid stress responses that do not exclude important gender effects in humans.
慢性应激存在于我们的日常生活中，被认为是许多疾病的诱因。许多与应激相关的疾病都表现出性别偏向。由于糖皮质激素是慢性应激的主要生物介质，研究人员一直致力于了解糖皮质激素应激反应中的性别二态性，以更好地解释应激相关疾病中的性别偏向。尽管尚未证明糖皮质激素调节存在性别差异，但性染色体在受孕后不久就会影响性别特异性生物学。然后，睾丸激素的短暂升高开始在产前阶段以不同于女性大脑的方式塑造男性大脑。这些组织效应在青春期前完成。参与静息和应激后糖皮质激素调节的大脑区域因此以性别特异性的方式受到影响。青春期后，所有性腺激素的高水平将通过各自的核受体与糖皮质激素激素进行特定的串扰相互作用。此外，生命早期发生的应激，特别是产前和青春期的应激，通过表观遗传机制在长期的糖皮质激素应激反应中引发，同样具有性别偏向性。总之，各种分子机制解释了性别特异性的糖皮质激素应激反应，这并不排除人类中重要的性别影响。
