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 ma le and female rats, we examined the effect of estradiol 17 beta on pro liferation. The index of cell proliferation was [H-3]thymidine uptake. Estradiol 17 beta (0.18-0.36 mu M) inhibited the uptake of thymidine in a concentration-dependent manner (p < 0.05). Estradiol 17 beta inhi bited [H-3]thymidine uptake only in the absence of the weak estrogen r eceptor agonist phenol red and in carotid artery segments from sexuall y mature female (p < 0.01) but not male rats. Tamoxifen (0.1 and 1 mu M), a partial agonist of estrogen receptors, significantly inhibited t hymidine uptake (p < 0.01). However, preincubation of the segments wit h tamoxifen (0.1 and 1.0 mu M) 4 h before the exposure to estradiol, b locked estradiol 17 beta-induced inhibition of thymidine uptake (p < 0 .05 and p < 0.01 for 0.1 and 1.0 mu M, respectively). The cyclooxygena se inhibitor indomethacin (5 mu M) did not affect either the basal [H- 3]thymidine uptake or the estradiol 17 beta-induced inhibition of that uptake. This latter finding suggests that prostacyclin or prostagland in E(2) does not mediate the inhibitory response to estradiol 17 beta. The results of these experiments suggest that estradiol 17 beta-induc ed inhibition of proliferation of rat carotid artery segments is media ted through activation of estrogen receptors.