RECEPTORS FOR ANDROGEN-BINDING PROTEINS - INTERNALIZATION AND INTRACELLULAR SIGNALING

In plasma, most steroid hormones are bound and transported by the spec ific binding protein, testosterone-estradiol-binding globulin (TeBG). For years, it was believed that the only function of this protein was to regulate the concentration of free steroids in plasma. However, a n umber of reports have provided evidence for the presence of specific T eBG receptors on plasma membranes. Furthermore, the interaction of TeB G with its receptor was shown to be inhibited when steroids are bound to TeBG, suggesting that TeBG is an allosteric protein. The purpose of this manuscript is to review the evidence that androgen-binding prote ins bind to membrane receptors, and, in some cells, this binding stimu lates cAMP accumulation, and transfer TeBG/ABP into tissue as a conseq uence of receptor mediated endocytosis. Recent studies from our labora tories have demonstrated binding and uptake of TeBG by MCF-7 breast ca ncer cells. The interaction of unligated rabbit TeBG with membranes fr om MCF-7 cells resulted in a time and concentration-dependent increase in adenylate cyclase activity. The TeBG alone also had a reproducible effect on intact cells by increasing cAMP accumulation by 30-35%. The addition of DHT to cells, after TeBG has been allowed to bind, result ed in increases in cAMP of greater than 4-fold. This effect was not bl ocked by antiandrogens. These data support the hypothesis that extrace llular SHBG is a regulator of cellular function through a membrane rec eptor that is coupled to adenylate cyclase.