Sex steroids as mediators of phenotypic integration, genetic correlations, and evolutionary transitions.

In recent decades, endocrinologists have increasingly adopted evolutionary methods and perspectives to characterize the evolution of the vertebrate endocrine system and leverage it as a model for developing and testing evolutionary theories. This review summarizes recent research on sex steroids (androgens and estrogens) to illustrate three ways in which a detailed understanding of the molecular and cellular architecture of hormonally mediated gene expression can enhance our understanding of general evolutionary principles. By virtue of their massively pleiotropic effects on the expression of genes and phenotypes, sex steroids and their receptors can (1) structure the patterns of phenotypic variance and covariance that are available to natural selection, (2) alter the underlying genetic correlations that determine a population's evolutionary response to selection, and (3) facilitate evolutionary transitions in fitness-related phenotypes via subtle regulatory shifts in underlying tissues and genes. These principles are illustrated by the author's research on testosterone and sexual dimorphism in lizards, and by recent examples drawn from other vertebrate systems. Mechanistically, these examples call attention to the importance of evolutionary changes in (1) androgen- and estrogen-mediated gene expression, (2) androgen and estrogen receptor expression, and (3) the distribution of androgen and estrogen response elements in target genes throughout the genome. A central theme to emerge from this review is that the rapidly increasing availability of genomic and transcriptomic data from non-model organisms places evolutionary endocrinologist in an excellent position to address the hormonal regulation of the key evolutionary interface between genes and phenotypes.