Sex hormone-binding globulin mediates steroid hormone signal transduction at the plasma membrane.

Sex hormone-binding globulin is a plasma glycoprotein that binds certain estrogens and androgens with high affinity. Over the past several years it has been shown that, in addition to functioning as a regulator of the free concentration of a number of steroid hormones, SHBG plays a central role in permitting certain steroid hormones to act without entering the cell. The system is complex. SHBG interacts with a specific, high affinity receptor (R(SHBG)) on cell membranes that appears to transduce its signal via a G protein. The SHBG-R(SHBG) complex causes the activation of adenylyl cyclase and the generation of cAMP within a matter of minutes after exposure to an appropriate steroid. Only steroids that bind to SHBG can activate SHBG-R(SHBG), but not all steroids that bind have this function, e.g. are agonists. All steroids that bind to SHBG but do not activate adenylyl cyclase are antagonists. The signals generated by the steroid-SHBG-R(SHBG) complex generate messages that have effects on the transcriptional activity of classic, intracellular receptors for steroid hormones. These and other downstream effects of this system are reviewed.