Estrogen receptor beta mediates the inhibitory effect of estradiol on vascular smooth muscle cell proliferation.
OBJECTIVE
It has been demonstrated that 17beta-estradiol (E2) has an inhibitory effect on the proliferation of vascular smooth muscle cells (VSMCs) through an estrogen receptor (ER)-dependent pathway. Both ER subtypes, classical ER (ERalpha) and the newly identified ER subtype (ERbeta), are expressed in VSMCs. However, it remains unknown which receptor plays the critical role in the inhibitory effect on VSMC proliferation.


RESULTS
We constructed replication-deficient adenoviruses bearing the coding region of human ERalpha, ERbeta, and the dominant-negative form of ERbeta (designated AxCAERalpha, AxCAERbeta, and AxCADNERbeta, respectively). Prior to infection with the adenoviruses, 100 nmol/l E2 attenuated DNA synthesis by up to 14% and transactivated the estrogen-induced expression of the desired mRNA in rat VSMCs. This was accompanied by increased transcriptional activity of estrogen responsive element in response to E2, and the increase was comparable between AxCAERalpha and AxCAERbeta. When VSMCs were infected with AxCAERbeta at a multiplicity of infection of 5 or higher, DNA synthesis as well as cell number decreased by 50% in response to E2, and the effect was abolished by co-infection with AxCADNERbeta. In contrast, when VSMCs were infected with AxCAERalpha, the reduction in DNA synthesis was minimal.


CONCLUSIONS
Our results indicate that ERbeta is more potent than ERalpha in the inhibitory effect on VSMC proliferation.
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D019925:Cyclin A / Q000378:metabolism; D003864:Depression, Chemical; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005822:Genetic Vectors / Q000008:administration & dosage; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014161:Transduction, Genetic / Q000379:methods
D019925:Cyclin A; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011960:Receptors, Estrogen; D004958:Estradiol; D008156:Luciferases