Neuroactive steroids in the fetal brain: role in the regulation of behaviour and protection against hypoxia

类固醇激素的主要分解产物孕酮形成一组称为神经活性类固醇的激素。这些类固醇对大脑活动有重大影响，并影响成年受试者的行为。类固醇产生腺体产生类固醇的变化影响成人大脑中的神经类固醇水平。这可能会导致成年人的行为和情绪变化，导致经前压力和产后抑郁等状况。在胎儿期，胎盘释放大量的这些神经活性类固醇，并且在胎儿循环中发现高浓度的这些类固醇。我们已经证明，这些类固醇抑制胎儿大脑的活动，抑制觉醒，并在怀孕期间保持胎儿在睡眠状态。在这个建议中，我们调查的假设，胎儿大脑中的细胞修改大脑内的神经活性类固醇环境，以进一步抑制胎儿大脑的活动，在压力的时候，因此，保护大脑免受过度兴奋造成的损害。这些机制可以防止由于怀孕期间胎盘功能不全和出生时窒息造成的脑损伤。这些自然过程的增强可以形成治疗策略的基础，为高危妊娠中的胎儿大脑提供额外的保护。

The major breakdown products of the steroid hormone, progesterone, form a group of hormones termed neuroactive steroids. These steroids have major effects on the activity of the brain and influence behaviour in adult subjects. Changes in the production of steroids by the steroid producing glands influences neurosteroid levels in the adult brain. This in tern may cause behavioural and mood changes in adults, leading to conditions such as premenstrual stress and postnatal depression. In fetal life, the placenta releases large amounts of these neuroactive steroids and high concentrations of these steroid are found in the fetal circulation. We have shown that these steroids suppress the activity of the fetal brain, suppress arousal and maintain the fetus in a sleep-like state during pregnancy. In this proposal we investigate the hypothesis that cells in the fetal brain modify the neuroactive steroid environment within the brain so as to suppress fetal brain activity further during times of stress and, therefore, protect the brain from damage caused by excessive excitation. These mechanisms may prevent brain injury due to placental insufficiency during pregnancy and asphyxia during birth. The augmentation of these natural processes may form the bases for treatment strategies to provide additional protection for the fetal brain in high-risk pregnancies.