Molecular androgen memory in sex development

Sex specific development in the human comprises irreversible sexual differentiation of the external genitalia during embryogenesis, sexual maturation of secondary sex characteristics during puberty (e.g., sex specific body proportions, pubertal voice change) and eventually sex specific development of extragenital tissues and organs, including the brain. The presence or absence of androgens acting via the androgen receptor plays a key role therein. At the single cell level, androgens cause reversible short term changes of gene transcription by activating the androgen receptor. From a developmental perspective, this often leads to irreversible long-term changes of anatomy (e.g., sex-specific differentiation of the external genitalia) and function (e.g., sex-specific play behavior in children). These observations are discussed in the context of recent genome-wide gene expression studies and first published experimental data at the epigenome level. In essence, there is evidence for a molecular androgen memory at both the transcriptome and the epigenome level.