Sex Hormone-Binding Globulin Binding to Cell Membranes and Generation of a Second Messenger

I n plasma, most steroid hormones are largely bound and transported by two specific steroid-hormone-binding proteins, corticosteroid-binding globulin (CBG) and sex hormone-binding globulin (SHBG) (Siiteri et al, 1982; Englebienne, 1984; Westphal, 1986; Rosner, 1986; Brien, 1981; Mercier-Bodard et al, 1981). Although it is an oversimplification (see Mendel, 1989), it is fair to state that the prevailing view of the function of these proteins is to bind steroids and thus trap them in the plasma compartment. Only a small fraction of free steroids are available to diffuse passively out of the capillary bed and across cell membranes to initiate hormonal effects. The best evidence supports this notion of how steroid hormones exit the vascular space and enter cells. In the past few years, however, there is undeniable evidence of additional functions for the steroidbinding proteins. The major lines of evidence that led to this conclusion are reviewed here.