In vitro effect of oestradiol on thymidine uptake in pulmonary vascular smooth muscle cell: role of the endothelium.
1. The effect of different concentrations of oestradiol-17 beta (3-300 nM) on [3H]-thymidine uptake was studied in segments from canine pulmonary artery, and cultures of rat pulmonary vascular smooth muscle cells (VSMC). 2. Incubation with oestradiol-17 beta for 24 h, potentiated in a concentration-dependent manner [3H]-thymidine uptake in VSMC cultures. 3. Oestradiol-17 beta potentiated thymidine uptake by pulmonary arterial segments but only when the endothelium had been removed. Autoradiography showed dense incorporation of radioactive thymidine in the vascular smooth muscle cells of the media. 4. The non-steroidal oestrogen, stilboestrol (300 nM), also significantly potentiated [3H]-thymidine uptake, in both VSMC cultures and pulmonary artery segments. Testosterone was ineffective at a similar concentration. 5. Pre-incubation of the pulmonary VSMC with the anti-oestrogen tamoxifen (1 microM) antagonized the potentiating effect of oestradiol-17 beta on [3H]-thymidine incorporation. The effect of tamoxifen was less pronounced in pulmonary arterial segments. 6. These data suggest that oestrogen may promote proliferation of pulmonary VSMC. Endothelial injury or dysfunction may be an important factor in the expression of the oestrogenic effect. 7. We speculate that plasma oestrogen may be a contributing factor to the proliferative lesion observed in certain forms of pulmonary vascular injury in women.
Farhat
M Y
MY
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, D.C. 20007.
Vargas
R
R
Dingaan
B
B
Ramwell
P W
PW
D000818:Animals; D001345:Autoradiography; D004054:Diethylstilbestrol / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013629:Tamoxifen / Q000494:pharmacology; D013739:Testosterone / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism*
D013629:Tamoxifen; D013739:Testosterone; D004958:Estradiol; D004054:Diethylstilbestrol; D013936:Thymidine