Sex hormone-binding globulin and male sexual development

The masculinization of the brain, reproductive tract and many other structures is critically dependent on the testicular hormone, testosterone (T). In many species, T circulates bound with high affinity to sex hormone-binding globulin (SHBG). This protein has a wide phylogenetic distribution and SHBG or SHBG-like proteins are produced by the liver, testes, placenta, brain and other tissues. SHBG activity is detectable during gestation and its expression is both stage- and tissue-dependent. Although SHBG binds circulating androgens, it is argued that the trapping of steroids in the circulation is not the principal function of this protein. The specific binding and uptake of SHBG by various tissues has been observed and suggests that SHBG may directly affect the delivery of androgen signals to target tissues. Effects of SHBG on androgen metabolism, tissue retention, cellular targeting, and action are reviewed. Evidence to date indicates that SHBG is able to enhance or inhibit the uptake of androgens in a cell- and tissue-specific manner. Future work will be necessary to demonstrate whether such actions of SHBG are important for normal male reproductive development.