Effect of estrogen on vascular smooth muscle cells is dependent upon cellular phenotype.
To investigate the growth-regulating action of estrogen on vascular smooth muscle cells (SMC), effects of beta-17-estradiol (beta-E2) on phenotypic modulation and proliferation of rabbit aortic SMC were observed in vitro. At 10(-8)M, beta-E2 significantly slowed the decrease in volume fraction of myofilaments (Vv myo) of freshly dispersed SMCs in primary culture, indicating an inhibitory effect of beta-E2 on spontaneous phenotypic modulation of SMC from a contractile to a synthetic phenotype. Freshly dispersed SMCs treated with beta-E2 also had a relatively longer quiescent phase than control cells before intense proliferation occurred. This was in contrast to SMCs in passage 2 3 (synthetic state), where beta-E2-treated cells replicated significantly faster than untreated cells. beta-E2 also markedly enhanced the serum-induced DNA synthesis of synthetic SMCs in a concentration-dependent manner within physiological range (10(-10)to 10(-8)M). These findings indicate that the growth-regulating effect of estrogen on vascular SMC is dependent on the cell's phenotypic state. It delays the cell cycle re-entry of the contractile SMCs by retarding their phenotypic modulation: however, once cells have modulated to the synthetic phenotype, it promotes their replication.
Song
J
J
Centre for Research in Vascular Biology, Department of Anatomical Sciences, University of Queensland, Brisbane, Australia.
Wan
Y
Y
Rolfe
B E
BE
Campbell
J H
JH
Campbell
G R
GR
D000818:Animals; D002453:Cell Cycle; D002455:Cell Division; D004261:DNA Replication; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D010641:Phenotype; D011817:Rabbits; D013936:Thymidine / Q000378:metabolism
D004958:Estradiol; D013936:Thymidine