Brain intracrinology of allopregnanolone during pregnancy and hormonal contraception

Allopregnanolone (ALLO) has a crucial role in brain development and remodeling. Reproductive transitions associated with endocrine changes affect synthesis and activity of ALLO with behavioral/affective consequences. Pregnancy is characterized by an increased synthesis of progesterone/ALLO by the placenta, maternal and fetal brains. This suggests the critical role of these steroids in maternal brain adaptation during pregnancy and the development of the fetal brain. ALLO is brain protective during complications of pregnancy, such as preterm delivery or intrauterine growth restriction (IUGR), reducing the impact of hypoxia, and excitotoxic brain damage. Negative behavioral consequences of altered progesterone/ALLO maternal brain adaptation have been also hypothesized in the post-partum and targeting ALLO is a promising treatment. Hormonal contraception may alter ALLO action, although the effects are mostly related to a specific class of progestins. Understanding the interactions between ALLO and the endocrine environment is crucial for more effective and tailored hormonal treatments