Estradiol effect on rate of proliferation of rat carotid segments: effect of gender and tamoxifen.
Using organ culture of carotid artery segments from sexually mature male and female rats, we examined the effect of estradiol 17 beta on proliferation. The index of cell proliferation was [3H]thymidine uptake. Estradiol 17 beta (0.18-0.36 microM) inhibited the uptake of thymidine in a concentration-dependent manner (p < 0.05). Estradiol 17 beta inhibited [3H]thymidine uptake only in the absence of the weak estrogen receptor agonist phenol red and in carotid artery segments from sexually mature female (p < 0.01) but not male rats. Tamoxifen (0.1 and 1 microM), a partial agonist of estrogen receptors, significantly inhibited thymidine uptake (p < 0.01). However, preincubation of the segments with tamoxifen (0.1 and 1.0 microM) for 4 h before the exposure to estradiol, blocked estradiol 17 beta-induced inhibition of thymidine uptake (p < 0.05 and p < 0.01 for 0.1 and 1.0 microM, respectively). The cyclooxygenase inhibitor indomethacin (5 microM) did not affect either the basal [3H]thymidine uptake or the estradiol 17 beta-induced inhibition of that uptake. This latter finding suggests that prostacyclin or prostaglandin E2 does not mediate the inhibitory response to estradiol 17 beta. The results of these experiments suggest that estradiol 17 beta-induced inhibition of proliferation of rat carotid artery segments is mediated through activation of estrogen receptors.
Vargas
R
R
Department of Physiology & Biophysics, Georgetown University Medical Center, Washington D.C. 20007, USA.
Hewes
B
B
Rego
A
A
Farhat
M Y
MY
Suarez
R
R
Ramwell
P W
PW
D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D010637:Phenolsulfonphthalein / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000187:drug effects; D012737:Sex Factors; D013629:Tamoxifen / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D011960:Receptors, Estrogen; D013629:Tamoxifen; D004958:Estradiol; D010637:Phenolsulfonphthalein; D013936:Thymidine; D007213:Indomethacin