Fig. 3. Lipoprotein receptors mediate uptake of steroid hormones bound to carrier proteins. In the circulation, androgens are solubilized by the sex hormone binding globulin (SHBG). Cell-type-specific uptake of SHBG-bound androgens involves the recognition of SHBG by LRP2 (megalin), followed by receptor-mediated endocytosis. In a process that parallels endocytic uptake of cholesterol in lipoproteins (see Fig. 2A), the protein moiety (here SHBG) is degraded in lysosomes, while the steroid enters the cytoplasm to exert its action (the induction of nuclear androgen receptors). Similar hormone-uptake pathways have been documented for SHBG-coupled estrogens and vitamin D binding protein-bound 25-hydroxyvitamin D₃. PM, plasma membrane.