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Ovariectomized post-partum rats exhibit in vivo continuous stable myometrial activity with a frequency of 45--50 pressure cycles per h, and a mean maximum amplitude of 45--50 mmHg for many days. Oestradiol benzoate (5 micrograms) reduced the frequency of intra-uterine pressure cycles to 5 cycles per h by 20 h after treatment. The decrease in frequency was due to increased periods of uterine quiescence. Pretreatment with reserpine caused significant reductions in the concentration of uterine adrenaline and noradrenaline as measured by a fluorometric assay but had no effect on the extent or time-course of oestrogen-induced myometrial quiescence. Neither intravenous infusion of the adrenergic beta-blocker, propranolol, altered the extent or the time-course of the reduction of intra-uterine pressure cycles after oestrogen treatment. These results suggest that the mechanism by which oestrogen induces myometrial quiescence does not involve adrenaline mediation or alpha- or beta-adrenoceptor activation.

Within some 14 h of treatment with oestradiol benzoate (5 microgram), the intra-uterine pressure cycles in ovariectomized puerperal rats were almost abolished. However, treatment with 600 microgram actinomycin D 30 min before the administration of oestradiol benzoate interfered significantly with the inhibition of uterine mechanical activity during the following 14h. Treatment of rats with actinomycin D alone produced no significant fall in the frequency of pressure cycles. These results suggest that oestrogen inhibits myometrial activity in the rat through a mechanism which involves the synthesis of protein.

The amplitude, frequency and rate of rise of intra-uterine pressure cycles in rats (postpartum, ovariectomized) were unaffected by treatment with progesterone. Amplitude was also unaffected by a combination of treatments with progesterone and oestradiol-17 beta, which was adequate to ensure the survival of 84% of foetuses in ovariectomized pregnant rats. The failure of progesterone to influence myometerial activity could not be attributed to a lack of "true" progesterone receptors since these were present in the myometria of the test animals in concentrations exceeding those of oestrous animals. Evidence was obtained which suggested that a high-affinity binding protein, different from the "true" receptor may predominate in the myometrium of the pregnant rat. Oestradiol-17 beta in single or repeated doses of from 0.25 to 5 microgram, however, was found to reduce the frequency of pressure cycles but to increase significantly their rate of rise of pressure. There was a latency of 6--8 h in these effects of oestradiol. The possibility that inhibition of the myometrium by oestrogen may play a part in the preparation for parturition is discussed.

Porcine relaxin (250 guinea-pig units/mg) infused intravenously into anaesthetized rats at 20 micrograms/h reversibly abolished spontaneous intra-uterine pressure cycles yet left the myometrium responsive to oxytocin in doses of 4--8 mu. The inhibition was found to be primarily of the frequency, rather than of the amplitude, of pressure cycles. Relaxin (5 or 10 micrograms) was capable of completely suppressing uterine activity driven by prostaglandin F2 alpha infusion in oestrogen-treated ovariectomized rats. Whereas the beta-adrenergic blocker, propranolol, had no effect on relaxin-induced inhibition, phentolamine, an alpha-blocker, significantly delayed the relaxin effect. It is unlikely, however, that relaxin operates through an alpha-inhibitory receptor. The results show that relaxin acts primarily as a frequency modulator and is capable of antagonizing an exogenous myometrial stimulant.

Relaxin in doses of 5 microgram i.v. completed but reversibly abolishes "spontaneous' myometrial activity in anaesthetized ovariectomized rats. Similar levels of myometrial activity, evoked in oestrogen-treated rats (which normally have quiescent uteri) by infusions of oxytocin or prostaglandin F2alpha (PGF2alpha), were also reduced to complete quiescence by relaxin in small doses. However when spontaneous myometrial activity in untreated ovariectomized rats was slightly stimulated by oxytocin the uterus became completely refractory to the inhibitory effects of relaxin even at doses of 50 microgram. Relaxin was also ineffective in reducing myometrial activity in similar rats during intra-arterial infusion of PGF2alpha. It is suggested that the ability of relaxin to inhibit uterine smooth muscle during exogenous stimulation is oestrogendependent.