The control of sexual differentiation of the reproductive system and brain

This review summarizes current knowledge of the genetic and hormonal control of sexual differentiation of the reproductive system, brain and brain function. While the chromosomal regulation of sexual differentiation has been understood for over 60 years, the genes involved and their actions on the reproductive system and brain are still under investigation. In 1990, the predicted testicular determining factor was shown to be the SRY gene. However, this discovery has not been followed up by elucidation of the actions of SRY, which may either stimulate a cascade of downstream genes, or inhibit a suppressor gene. The number of other genes known to be involved in sexual differentiation is increasing and the way in which they may interact is discussed. The hormonal control of sexual differentiation is well-established in rodents, in which prenatal androgens masculinize the reproductive tract and perinatal oestradiol (derived from testosterone) masculinizes the brain. In humans, genetic mutations have revealed that it is probably prenatal testosterone that masculinizes both the reproductive system and the brain. Sexual differentiation of brain structures and the way in which steroids induce this differentiation, is an active research area. The multiplicity of steroid actions, which may be specific to individual cell types, demonstrates how a single hormonal regulator, e.g. oestradiol, can exert different and even opposite actions at different sites. This complexity is enhanced by the involvement of neurotransmitters as mediators of steroid hormone actions. In view of current environmental concerns, a brief summary of the effects of endocrine disruptors on sexual differentiation is presented.