Resolving the role of prenatal sex steroids in the development of digit ratio.

P renatal sex steroids [i.e., prenatal testosterone (PT), prenatal estrogen (PE)] are often implicated in the etiology of behaviors and diseases. They show sex differences (higher concentrations of PT to PE in males), with PT peaking at the end of the first trimester, and cause permanent “organizational” changes in the brain and other organ systems. It has been suggested that relative levels of PT and PE may have differential effects on fertility, speed, strength, aggression, autism, many cancers, and heart disease. However, PT and PE are difficult to assess, and this has prevented the establishment of convincing links. The relative lengths of the second and fourth digits [digit ratio (2D:4D)] is thought to correlate negatively with PT and positively with PE, thus affording us the possibility of establishing such links. Although associations between 2D:4D and many sexually dimorphic traits have been investigated, the developmental link between 2D:4D and PT and PE has remained controversial until now. In PNAS, Zheng and Cohn (1) present an elegant and powerful experimental examination of the influence of PT and PE on the development of 2D:4D in the mouse. To appreciate the relevance of their findings, it is necessary to consider them in the context of the recent history of 2D:4D research.