Chromosomal and hormonal factors involved in human sexual dimorphism

Males and females show significant differences in body structure, typical behavior, average life expectancy, and disease susceptibility. This review article introduces the current understanding and recent findings on the factors that lead to sexual dimorphism. First, recent studies have shown that sex chromosomes underlie male- and female-specific phenotypes through various mechanisms. For example, X chromosome inactivation exerts both positive and negative effects on female health, independent of sex hormone actions. Furthermore, differences in the frequency and clinical consequences of the mosaic loss of X and Y chromosomes have been implicated in sex differences in disease susceptibility and average life expectancy. In addition, sex-specific epigenetic regulation of the pseudoautosomal gene SHOX has been linked to the relative short stature of females. Second, an alternative steroidogenic pathway and novel non-aromatizable androgens have been specified in humans. These factors, together with classical sex hormones, likely contribute to the phenotypic differences between males and females. Elucidating the molecular basis of sexual dimorphism helps us understand the factors involved in human diversity.