Sex Hormone Binding Globulin (SHBG), in addition to regulating free concentrations of steroid sex hormones in plasma, also participates in membrane-based steroid signaling in breast and prostate cells. In this study, we address whether the breast and prostate can synthesize their own SHBG. SHBG mRNA and protein were detected in human breast and prostate cancer cell lines, as well as in normal and cancerous breast and prostate tissue where it was prominent in epithelial cells. In cultured human LNCaP prostate cancer cells, SHBG was found both in the cytoplasm, and on the outer cell membrane where it was presumably bound to its high affinity receptor (Rshbg)- When LNCaP cells were treated with 2-methoxyestradiol (2MeOE2), an antagonist of SHBG binding to Rshbg» membrane-associated SHBG was eliminated. These results demonstrate that the breast and prostate can synthesize SHBG locally, and that SHBG can bind to, and perhaps participate in autocrine and/or paracrine signaling through Rshbg- Therefore, perturbations in SHBG expression in breast and prostate tumors may affect the regulation of steroid signaling through and target SHBG-mediated biologic properties at the cellular level.

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