These sex hormones circulate in the bloodstream, bound mostly to SHBG and to some degree bound to albumin. Only a small fraction is unbound, or "free," and thus biologically active and able to enter a cell and activate its receptor. Thus bioavailability of sex hormones is influenced by the level of SHBG.
SHBG production
SHBG is produced by the liver cells and released into the bloodstream. Other sites that produce SHBG are the brain, uterus, and placenta. In addition SHBG is produced by the testis; testis-produced SHBG is also called androgen-binding protein. The gene for SHBG is located on chromosome 17.
Control
SHBG levels appear to be controlled by a delicate balance of enhancing and inhibiting factors. Its level is decreased by high levels of insulin and insulin-like growth factor-I (IGF-I). Also, high androgen levels decrease SHBG, while high estrogen and thyroxine levels increase it.
When determining levels of circulating estradiol or testosterone, either a total measurement could be done that includes the "free" and the bound fractions, or only the "free" hormone could be measured.
