The receptor-mediated action of sex steroid binding protein (SBP, SHBG): Accumulation of cAMP in MCF-7 cells under SBP and estradiol treatment

The interaction of sex steroid binding protein (SBP) with its specific receptor in MCF-7 cell (estrogen-sensitive human breast cancer cells), followed by the binding of estradiol (E 2) to the complex SBP-receptor, induced a significant accumulation of intracellular cAMP. SBP alone as well as E 2 alone did not elicit any modification of the nucleotide. The maximal increase in cAMP was observed with 1 nM SBP + 1 nM E 2. Increasin doses of both SBP and E 2, even raising cAMP levels with respect to basal, did not give any higher response. Both testosterone and dihydrotestosterone, used instead of E 2, were not able to induce any significant modification of cAMP. E 2-induced MCF-7 cell proliferation was significantly reduced by 8Br-cAMP, MDA-MB 231 cells (estrogen-insensitive breast cancer cells) were not shown to bind SBP, or to respond to SBP + E 2 as far as both their proliferation and cAMP content are concerned. In summary, the present study provides evidence that the SBP receptor is part of the G-protein receptor family, and that SBP can act as modulator of E 2 action at cell site through the second messenger cAMP. (Steroids 59:661–667, 1994)