Androgens Contribute to the Process of Neuronal Development: Implications in Explanation of Autism Pathogenesis

Fetal testosterone significantly influences the brain development. It affects number of neurons and conformation of dendritic spines within the sexual dimorphic preoptic area in the hypothalamus. Excessive testosterone levels in utero possibly contribute to the masculinization of the brain. Evidences of these facts are plausible in the anatomic field as well as behavioral effects both in rat models and in humans. Rats exposed to excessive testosterone doses in utero show masculinized brain anatomy and behavior, such as better spatial visualization performance typical for males. In humans, congenital adrenal hyperplasia that causes elevated androgen level possibly results in masculinized behavior observed in these individuals. There are reasons for the theory of the connection existence between testosterone influence on the brain functions and the pathogenesis of neurodevelopmental disorders. In this review, pathogenesis of autism, the most genetic neurodevelopmental disease is discussed. Autism is a disease with broad genetic heterogeneity and polygenic inheritance. Autism associated genes are localized throughout the genome, with the chromosome 7q most frequently involved. One of these genes encodes reelin protein that is crucial for neuronal migration in the developing brain. The connection between androgens, neuronal migration and neurodevelopmental disorder pathophysiology is also discussed. ORIGINAL ARTICLE S. Kelemenova, D. Ostatnikova 4