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

Sex hormone-binding globulin is a plasma glycoprotein that binds certain es trogens and androgens with high affinity. Over the past several years it ha s been shown that, in addition to functioning as a regulator of the free co ncentration of a number of steroid hormones, SHBG plays a central role in p ermitting certain steroid hormones to act without entering the cell. The sy stem is complex. SHBG interacts with a specific, high affinity receptor (R- SHBG) on cell membranes that appears to transduce its signal via a G protei n. The SHBG-R-SHBG complex causes the activation of adenylyl cyclase and th e generation of cAMP within a matter of minutes after exposure to an approp riate steroid. Only steroids that bind to SHBG can activate SHBG-RSHBG, but not all steroids that bind have this function, e.g. are agonists. All ster oids that bind to SHBG but do not activate adenylyl cyclase are antagonists . The signals generated by the steroid-SHBG-R-SHBG complex generate message s that have effects on the transcriptional activity of classic, intracellul ar receptors for steroid hormones. These and other downstream effects of th is system are reviewed. (C) 1999 Elsevier Science Ltd. All rights reserved.