Androgen and estrogen signaling at the cell membrane via G-proteins and cyclic adenosine monophosphate

Androgens and estrogens are well-known to initiate their actions by binding to specific intracellular receptors. The steroid-receptor interaction, the receptors, and the details of transcriptional activation consequent to the binding of these steroids with their respective receptors have been, and c ontinue to be, intensively studied. More recently, it has become increasing ly apparent that steroids may interact with cells by other than this classi c pathway. This communication will deal with activation by sex hormones of a signal transduction pathway that originates at the cell membrane and util izes cyclic adenosine monophosphate (cAMP) as a second messenger. The syste m consists of three components, an agonist steroid, sex hormone-binding glo bulin (SHBG), and a membrane receptor (R-SHBG) for SHBG. SHBG is a well-cha racterized plasma protein that has two binding sites, one binds certain est rogens and androgens, and the other binds to R-SHBG. The characteristics of this novel signal transduction system, from the interaction of SHBG with R -SHBG, to the intermediacy of G-proteins, to cAMP generation, to downstream effects of the second messenger will be reviewed. (C) 1999 Elsevier Scienc e Inc. All rights reserved.