Sex Hormonebinding Globulin

Of the circulating testosterone in adult men, approx 45% is bound with high affinity to SHBG, 50% is loosely bound to albumin (Alb), 1-2% is bound to cortisol-binding globulin, and less than 4% is free (not protein bound) (3). SHBG is a carbohydrate-rich P-globulin produced by hepatocytes. It is a 100,000-kDA dimer, with protomers of 48-52 kDA that convert to a single 39 kDA species when deglycosylated and fractionated on a polyacrylamide gel (4). SHBG binds testosterone and other steroids with high affinity and prolongs their metabolic clearance (5). Because of SHBG's role as a plasma testosterone binding protein, there is a positive correlation between its level and the level of testosterone in human adult male plasma, such that total testosterone levels are low when SHBG levels are low (see Fig. 1). The general view is that SHBG reduces the cellular uptake of androgens from the plasma compartment (6) and negatively regulates availability to target cells (7). On the other hand, the finding of membrane binding sites for SHBG in testis, prostate, and other tissues (8) and the identification of SHBG mRNA and protein in human prostate cancer cell lines and cultured human prostate epithelial and stromal cells (9) suggest a paracrine function of SHBG after ligand activation that could directly influence androgen action.

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