Abstract
In 2001 the Institute of Medicine of the National Academy of Sciences United States published a report, “Exploring the Biological Contributions to Human Health: Does Sex Matter?”, which addressed and highlighted the role of biological sex differences in health and disease, including especially sex differences in non-reproductive areas of the male and female. The report aroused considerable interest and comment and had a significant role in stimulating the generation of a growing body of basic and clinical research on fundamental aspects of sex differences and its role in disease susceptibility, development, and aging. Sex is the most common human polymorphism that affects health and illness through the life cycle.
This perspective provides a brief overview of the importance of the critical interlinked interactions of nature (genes and sex hormones) and nurture (environment and experience) on behavior and perception. Differences in gene expression in the male and female appear in the early embryo, before differentiation of the fetal gonads into a testis or ovary, the latter a consequence of the testis-determining SRY gene on the Y chromosome (a developmental switch). Gonadal differentiation results in a striking sex difference in the fetal sex steroid milieu and the phenotypic differences in the internal and external genital tracts that follows. Recent data provide evidence that in addition to the classic brain masculinizing effects of testosterone in the fetus, XX and XY brain cells show different patterns of gene expression even before gonadal differentiation. The functional and structural significance and magnitude of these brain sex differences are uncertain. The X chromosome contains a higher number of genes that have a major role in the development of general cognitive ability. Further, we now know that estrogen formed mainly in extragonadal tissues has an important multifaceted role in boys at puberty and in men.
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