Effects of diethylstilboestrol and ovarian steroids on the contractile responses and calcium movements in rat uterine smooth muscle

Abstract

1. The synthetic oestrogen diethylstilboestrol had a potent inhibitory effect on the mechanical responses of the rat uterus. The spontaneous contractions were reduced in amplitude by 2 microgram and were completely abolished by 20 microgram diethylstilboestrol. The amplitude of contractions induced by acetylcholine (ACh) was also considerably reduced in the presence of 20 microgram of the compound. 2. Oestradiol (oestradiol-17 beta) had a weaker, and progesterone a negligible, effect on the spontaneous contractions. 3. In the depolarized (induced by high potassium) uterus, the log concentration response curve for contraction induced by Ca was sigmoidal and reached its maximum at about 1 mM-Ca. These responses to Ca were greatly depressed by oestradiol and progesterone and were again completely abolished by diethylstilboestrol. All three compounds were also able to induce a relatively rapid relaxation in preparations contracted by Ca. 4. Inhibition of the ACh contraction in the depolarized uterus by diethylstilboestrol, oestradiol and progesterone had the characteristic of blocking the second, and relatively slow, phase of the contraction without influencing the first rapid response. A similar pattern of inhibition was observed in the presence of D-600 or EGTA. 5. The lanthanum method gave only an approximate measure of cellular Ca in the rat uterus, since La failed to block 45Ca efflux and was unable effectively to displace extracellular 45Ca. 6. Diethylstilboestrol reduced the influx of 45Ca both in normal and depolarizing media but did not affect 45Ca efflux. 7. These results indicate that oestrogens and progesterone are able to decrease Ca entry into the uterine cells, which probably accounts for their inhibitory effect on the contractile activity. The mechanism by which these agents induce relaxation of a contracted uterus also seems to depend on the inhibition of Ca influx.