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SUMMARY
Radioactive [14C]5-hydroxytryptamine (5-HT, serotonin) creatinine sulphate was injected intrapleurally into female rats treated with oestrogen and/or progesterone which had received, immediately before the injection of 5-HT, homogenates of placenta, foetus, uterus or plasma, taken from pregnant rats on the 19th day of pregnancy. The placental homogenate produced a significant increase in 5-HT uptake by the myometrium, when the rats had been primed with moderate doses of oestrogen plus progesterone. Higher doses prevented the increased uptake, and oestrogen treatment alone did not induce 5-HT uptake. The highest level of 5-HT accumulation in the uterus was produced by placental extract after pretreatment with 0·5 mg. oestradiol plus 10 mg. progesterone/rat/day.
These results suggest that the placenta contains a 'trans-serotonin' system which is dependent on the oestrogen—progesterone balance and serves to accumulate 5-HT in the placenta and myometrium. Shifts of the hormonal balance may contribute to the release of 5-HT and thus promote uterine contractions at any stage of pregnancy.
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SUMMARY
Intra-aortic injection of [3-14C]5-hydroxytryptamine creatinine sulphate ([14C]5-HT) into oestrogen or oestrogen-progestogen treated rats showed a pattern of homogeneous uptake similar to that found in untreated normal rats. In pregnant rats the injection resulted in a preferential uptake by the myometrium. Injection of a MAO inhibitor (pargyline hydrochloride, Eutonyl) into the amniotic sac, preceding the [14C]5-HT injection by 30 min., changed this pattern to a preferential accumulation in the myometrium and the spleen, perhaps due to unhampered transport of preserved 5-HT by the thrombocytes to the spleen. When [14C]5-HT was injected i.p. into the foetuses they retained high amounts of exogenous 5-HT. Myometrium and placenta also showed increased 5-HT uptake.
This finding—taken together with the established fact that foetal 5-HT increases and placental monoamine oxidase decreases steadily up to term—suggests that at term the release of foetal 5-HT may enrich the maternal myometrium with 5-HT through the umbilical arteries without its entering the general blood circulation. It is also possible that additional maternal 5-HT may accumulate in the myometrium sensitized by the oestrogen surge at term. The importance of these mechanisms for the induction of labour is discussed.
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SUMMARY
Subcutaneous injection of the 5-hydroxytryptamine (5-HT) antagonist cyproheptadine hydrochloride (Periactin) produced a significant decrease in uptake of [14C]5-HT (serotonin) in the myometrium and to a lesser degree in the ovaries, foetuses and heart of pregnant rats. This effect of cyproheptadine was considerably increased in rats pretreated with the monoamine oxidase inhibitor pargyline hydrochloride. These results suggest that the anti-abortive effect of cyproheptadine is based on specific inhibition of the contractile effect of 5-HT on the myometrium. The hypothesis is advanced that cyproheptadine competes with serotonin for its receptors and thus blocks the effect of serotonin.
