ROSNER, W.; HRYB, D.J.; KAHN, S.; KHAN, M.S.; NAKHLA, A.M.; ST. GEORGE, J.: Sex Hormone-binding Globulin as an Intermediate in Sex Steroid Signaling at the Cell Membrane
In plasma, certain androgens and estrogens are bound to sex hormone-binding globulin (SHBG) with high affinity. SHBG not only regulates the concentration of free androgens and estrogens in plasma but binds to a specific receptor, RSHBG, on certain cell membranes, forming an SHBG-RSHBG complex. This complex is activated by an appropriate steroid hormone (in a tissue specific manner) such as dihydrotestosterone (DHT), 5&alpa-androstan,3&alpha,17&beta diol (3&alpha diol) or estradiol, to activate a second messenger system to produce cAMP after the steroid binds, e.g. after the complex, steroid-SHBG-RSHBG forms. Further, in whole non-cancerous explants of human prostate, the system causes increases in the secretion of prostate specific antigen (PSA), an event previously thought to be related only to the activation of the androgen receptor (AR) by DHT. All of the studies dealing with activation of RSHBG by SHBG and an appropriate steroid assumed that SHBG was delivered to cells via the plasma. We will review the evidence for all of the foregoing and, in addition, present data which support the hypothesis that SHBG is produced either by cells that themselves express RSHBG or are adjacent to cells that express RSHBG. The context of this new model attaches importance to the autocrine and paracrine regulation of SHBG as a regulator of sex steroid action at the cell membrane.
