Mechanisms of specific change by estradiol in sensitivity of rat uterus to serotonin.

The sensitivity (contractile response) to serotonin (5-HT) of the isolated rat uterus was increased either during estrus or by administration of estradiol to ovariectomized rats. These increases in sensitivity to 5-HT were specific, because the sensitivities to acetylcholine and oxytocin were not influenced in either case. Pargyline (10(-5) M), an inhibitor of monoamine oxidase, did not affect the contractile responses to 5-HT, acetylcholine and oxytocin of uterus from ovariectomized rats. The monoamine oxidase activities in 100,000 X g precipitates and supernatants of homogenates for uteri from ovariectomized rats were either increased or unchanged by administration of estradiol. The contractile response to 5-HT of the uterus of untreated ovariectomized rats was not affected by chlorimipramine at 10(-6) M, a concentration that inhibits 5-HT uptake. Administration of estradiol increased significantly the number of [3H]spiroperidol binding sites (5-HT receptors) from 0.56 +/- 0.04 to 1.23 +/- 0.11 pmol/mg of protein, but did not change the apparent affinity of 5-HT receptors. Administration of estradiol did not change the dissociation constant or number of binding sites for [3H]quinuclidinyl benzilate (muscarinic acetylcholine receptors) significantly. These results indicate that the specific increase in sensitivity to 5-HT on administration of estradiol is due to change in the number of 5-HT receptors, but not to change in 5-HT uptake or in metabolic degradation of 5-HT.