17 beta-estradiol inhibits cardiac fibroblast growth through both subtypes of estrogen receptor.
The effect of 17 beta-estradiol (E2) on the proliferation of cardiac fibroblasts (CFs) remains controversial. This study investigated which subtype of estrogen receptor (ER), ER alpha or ER beta, mediated the effect of E2 on CF growth by the gain of function analysis using an adenovirus vector. One hundred nanomoles per liter of E2 attenuated DNA synthesis by up to 10%, and transactivated the estrogen-responsive element determined by luciferase assay in rat neonatal CFs. We constructed replication-deficient adenoviruses bearing the coding region of human ER alpha, ER beta, or the dominant-negative form of ER beta (designated AxCAER alpha, AxCAER beta, and AxCADNER beta, respectively). When CFs were infected with AxCAER alpha or AxCAER beta at multiplicity of infection of 20 or higher, DNA synthesis was decreased by 50% in response to E2 and the effect was abolished by co-infection with AxCADNER beta. Similarly, transcriptional activity of ER in CFs infected with AxCAER alpha or AxCAER beta was markedly enhanced and co-infection with AxCADNER beta abolished the effects. These results suggest that E2 inhibits CF growth and that both ER subtypes mediate the effect comparably and redundantly.
Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
Tokumitsu
T
Watanabe
Masahiro
M
Akishita
Hong
H
He
Yukiko
Y
Miyahara
Koichiro
K
Nagano
Takashi
T
Nakaoka
Naohide
N
Yamashita
Koichi
K
Kozaki
Yasuyoshi
Y
Ouchi
D000818:Animals; D000831:Animals, Newborn; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000378:metabolism*
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011960:Receptors, Estrogen; D004958:Estradiol