Sex hormone-binding globulin receptor signal transduction proceeds via a Gprotein

The plasma protein, sex hormone-binding globulin (SHBG) binds to a receptor (R-SHBG) on cell membranes to form an SHBG-R-SHBG complex. When an appropr iate steroid binds to this complex, there is a rapid rise in intracellular cyclic adenosine monophosphate (cAMP). Although the system is moderately we ll characterized, the molecular cloning of R-SHBG has not been accomplished and there is a paucity of evidence regarding the mechanism of transmission of the R-SHBG signal. In this communication, we offer two independent line s of evidence that a G protein is involved in R-SHBG signal propagation. Ex posure of cell membranes containing R-SHBG to a non-hydrolyzable analog of guanosine triphosphate (guanylyl-5'-imidodiphosphate) caused a substantive decrease in the binding of SHBG to R-SHBG. This behavior is typical of memb rane receptors coupled to G proteins and has been used by others as evidenc e to support that relationship. Another set of experiments involved the ass umption that, if R-SHBG-induced increases in cAMP were diminished when the wild-type alpha subunit of a G protein was replaced with mutants that were inefficient/ineffective in signal transduction, then the idea that G protei ns were involved in that signal would be buttressed. Hence, we infected COS -1 cells with a construct containing such mutants, along with a cAMP respon se element reporter, and demonstrated a marked decrease in R-SHBG-engendere d reporter activity, e.g. cAMP generation. (C) 1999 Elsevier Science Inc. A ll rights reserved.