Fissore F, Fortunati N, Comba A, Fazzari A, Gaidano G, Berta L, Frairia R
II Divisione Universitaria di Medicina Generale, University of Torino Medical School, Italy.
Steroids. 1994 Nov;59(11):661-7. doi: 10.1016/0039-128x(94)90023-x.
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 (E2) to the complex SBP-receptor, induced a significant accumulation of intracellular cAMP. SBP alone as well as E2 alone did not elicit any modification of the nucleotide. The maximal increase in cAMP was observed with 1 nM SBP + 1 nM E2. Increasing doses of both SBP and E2, even raising cAMP levels with respect to basal, did not give any higher response. Both testosterone and dihydrotestosterone, used instead of E2, were not able to induce any significant modification of cAMP. E2-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 + E2 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 E2 action at cell site through the second messenger cAMP.
性类固醇结合蛋白（SBP）与其在MCF-7细胞（雌激素敏感的人乳腺癌细胞）中的特异性受体相互作用，随后雌二醇（E2）与SBP-受体复合物结合，诱导细胞内cAMP显著积累。单独的SBP以及单独的E2均未引起核苷酸的任何改变。在1 nM SBP + 1 nM E2时观察到cAMP的最大增加。SBP和E2剂量增加，即使相对于基础水平提高了cAMP水平，也未产生更高的反应。用睾酮和二氢睾酮代替E2，均不能诱导cAMP的任何显著改变。8Br-cAMP显著降低了E2诱导的MCF-7细胞增殖。就MDA-MB 231细胞（雌激素不敏感的乳腺癌细胞）而言，未显示其能结合SBP，或对SBP + E2在增殖和cAMP含量方面产生反应。总之，本研究提供了证据表明SBP受体是G蛋白受体家族的一部分，并且SBP可通过第二信使cAMP在细胞位点充当E2作用的调节剂。
