Hormone-Dependent Chromatin Modifications Related to Sexually Differentiated Behaviors

摘要

Behaviors associated with reproduction depend on brain mechanisms which are the most extremely differentiated between the sexes. This article will describe those brain mechanisms, with an emphasis on sexually differentiated regulation of gene expression in the neurons of the hypothalamus. In turn, hormone-dependent transcriptional activation is regulated by changes in chromatin, histone proteins the tails of which are subject to several forms of chemical modification. We will describe specific examples of histone tail acetylation and methyla-tion as they influence reproductive behavior and sex differences in the brain. Finally, we must ask: under what circumstances are sex differences in brain and behavior most important? Thinking that sexually differentiated maladies answer that question, we will propose a 3-hit theory of the large sex difference in autism: (1) genetic predispositions, followed by (2) androgenic hormone effects on CNS arousal systems and limbic forebrain, in young males; followed in turn by (3) deleterious effects of early stress. These three types of mechanisms yield the 'extreme male brain' of the autistic boy.