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D. G. PORTER

Myometrial activity is not completely inhibited during pregnancy in the guineapig, but it is reduced to a level significantly below that of the non-pregnant animal (Porter, 1971). In view of a recent finding (Porter, 1969, 1970) that progesterone was totally without effect on myometrial activity in vivo in the pregnant and non-pregnant guinea-pig, it seemed possible that relaxin might be implicated in the mechanism by which myometrial activity is reduced in pregnancy in this species. This hormone increases in concentration in the serum during pregnancy in guinea-pig (Zarrow, 1947) and inhibits guinea-pig uterine contractions in vitro (Felton, Frieden & Bryant, 1953). A study was carried out therefore on the effects of the hormone in vivo.

Non-pregnant guinea-pigs in various stages of the oestrous cycle were equipped with intrauterine recording balloons according to a method described earlier

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D. G. PORTER

Summary.

The effect of altering the light regimen after copulation upon the duration of pregnancy in mice was investigated. It was found that mice bore young at a constant interval after copulation irrespective of the prevailing light conditions. No evidence was obtained that a light-dependent circadian mechanism determined the delivery time, although the possibility that such a mechanism might be established in the period immediately before mating was not ruled out by the present study. A significant negative correlation of litter size on gestation length was noted.

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D. G. PORTER

Summary.

Parturition in mice implanted with pellets of oestradiol on Day 16 of pregnancy occurred 1 day later than in cholesterol-treated controls. This prolongation of pregnancy was attributed to a reduction in the litter size occurring pre-partum due to `jettisoning' of an average of 2·2 foetuses per mouse. Progesterone treatment was only partially effective in preventing the oestrogen-induced foetal loss.

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D. G. PORTER

Summary.

Intrauterine pressure recordings were made in non-pregnant guinea-pigs, and in either the gravid horn of bilaterally pregnant, or the sterile horn of unilaterally pregnant animals. The results showed that, rather than a reduction of uterine activity during the luteal phase of the oestrous cycle, there was a significant increase compared with the level at oestrus. Activity during pregnancy was reduced compared with nonpregnant levels and this reduction was accomplished by a lowered frequency of pressure cycles while their amplitude remained unchanged. The activity of the gravid horn was significantly less than that of the sterile horn during the mid-third of pregnancy. Both the sterile and gravid horns responded to oxytocin at all stages of pregnancy. From these results, it is suggested that progesterone may not be a myometrial regulatory agent in the guinea-pig.

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D. Claire Wathes and D. G. Porter

Summary. Gap junctions were present in the myometrium of 1 out of 5 rats on Day 21 of pregnancy, 4 out of 5 on the morning of Day 22, 7 out of 7 during parturition and 1 out of 3 on Day 1 post partum. Their frequency (number per mm membrane) at these time periods increased from 0·30 to 2·20 and 6·48 and then decreased to 0·31.

Ten ovariectomized post-partum rats were fitted with an intrauterine balloon in one horn for recording pressure changes. Control rats maintained continuous pressure cycles. In rats given 7·5 μg oestradiol-17β the frequency of intrauterine pressure cycles decreased from about 50 per hour to 4·3 per hour 15 h later, but the maximum rate of rise of uterine pressure cycles increased significantly from 7·2 ± 0·95 to 11·3 ± 1·85 mmHg sec−1 (n = 5, P < 0·05). The overall number of gap junctions per mm membrane in the oestrogen-treated rats was 7·37 in the horns equipped with balloons and 1·03 in the empty horns, compared with 0·97 and none respectively in the control rats. The increased rate of rise of pressure in the oestrogen-treated myometrium indicated improved coupling between cells and this was associated with a high frequency of gap junctions. Both oestrogen treatment and distension (from the balloon) appeared to cause some gap junctions to form, but numbers equivalent to those at parturition were only obtained in animals in which these two treatments were combined.

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D. G. Porter and A. D. Watts

Summary. Intravenous bolus injections of pig relaxin which produced short-lived peaks of the hormone equivalent in concentration to those observed at term promptly rendered the uterus almost totally quiescent and the inhibition persisted for about 2·5 h. During this time the uterus remained responsive to oxytocin. The main effect of relaxin was to reduce the frequency of intrauterine pressure cycles rather than the amplitude. In contrast progesterone, which also inhibited myometrial activity, took between 6 and 24 h to exert its maximum effect by reducing both amplitude and frequency of IUP cycles and it also abolished the responsiveness of the myometrium to oxytocin. Its actions were reversible but recovery took between 54 and 140 h. Oestradiol benzoate had no significant effect on myometrial activity in 21 out of 26 treatments. At 24 h after the 5 remaining treatments, however, myometrial activity was virtually zero. No evidence was obtained of a biphasic effect of oestradiol on myometrial activity as reported for the rat and ewe. This work demonstrates that purified pig relaxin is an active myometrial inhibitor in the oestrogen-treated ovariectomized non-pregnant pig in vivo.

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D. G. PORTER and J. R. G. CHALLIS

In a pilot experiment to test the feasibility of studying the progesterone 'block' in a species other than the rabbit, it was found that the myometrial activity of the post-partum rat recorded in vivo by means of small indwelling recording balloons was not reduced following intramuscular injections of progesterone (10 mg in oil). In view of the ample evidence that progesterone is essential in maintaining pregnancy in the rat after ovariectomy (Johnson & Challans, 1930; Rothchild & Meyer, 1940), this paradoxical finding was investigated in more detail.

On the day following parturition, six Holtzman rats were anaesthetized with tribromoethanol intraperitoneally and a small latex recording balloon attached to a polyethylene catheter (0·015 in. i.d. × 0·043 in. o.d.) was placed in one uterine horn through a

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S. J. Lye and D. G. Porter

Summary. Intrauterine pressure was monitored in vivo in oestrogen-treated ovariectomized ewes before, during and after treatment with progesterone (50 mg s.c./day for 3 days). Progesterone reversibly reduced the frequency and amplitude of myometrial activity and abolished uterine reactivity to oxytocin (i.v.) and PGF-2α (intrauterine infusion). The rate of rise of intrauterine pressure during active pressure cycles was significantly reduced. These results confirm that the action of progesterone on the ovine myometrium is comparable to the classic progesterone 'block'. The intrauterine infusion of PGF-2α (10 μg/min), which elicited a marked mechanical response in the control animals, failed to stimulate the progesterone-'blocked' uterus, suggesting that the inhibition produced by progesterone is due to a direct action of the hormone on the uterine muscle and not to an indirect mechanism operating through endometrial prostaglandin output.

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D. G. Porter and Sandra J. Downing

Summary. When post-partum ovariectomized rats were linked to 21-day-pregnant rats by a cross-circulation system their myometrial activity was almost completely inhibited. No reduction in activity was induced by cross-circulation with other post-partum rats, or with rats in which myometrial activity had been suppressed with oestrogen. Changes in uterine activity could not be correlated with alterations in arterial blood pressure occurring during the experiments. Uteri rendered inactive by cross-circulation were found to be responsive to oxytocin. It is concluded that a humoral myometrial inhibitor is present in late pregnancy in rat blood and the possibility that it is relaxin is discussed.

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D. G. PORTER, R. BECKER, and A. CSAPO

Summary.

A study was made into the effects of hypertonic saline upon the intra-uterine pressure in non-pregnant and pregnant rabbits. In non-pregnant rabbits intra-luminal administration of hypertonic saline caused an almost immediate transient increase in amplitude and frequency of uterine pressure cycles, a response which was abolished by prior treatment with progesterone. In pregnant rabbits, provided all placentae were damaged by the treatment, intra-amniotic administration of 20% NaCl resulted in abortion of all foetuses in 56 ± 7·3 hr SE. If one conceptus escaped damage pregnancy was not interrupted. Furthermore, treatment with 25 μg/day oestradiol propionate prevented abortion. Of the procedures carried out, only dislocation of the placentae also caused abortion, whereas pregnancy was not terminated by extra-amniotic administration of hypertonic saline, by cutting the umbilical cords (i.e. causing foetal death), nor by the intra-amniotic administration of normal (0·9%) saline. The abortion produced by both intra-amniotic hypertonic saline and dislocation of the placentae could be prevented by oestrogen administration, but not if ovariectomy were combined with placental dislocation. From these results, it is concluded that intra-amniotic hypertonic saline induced abortion in rabbits by interrupting the luteotrophic function of the placenta which resulted in loss of the luteal function essential for the defence of pregnancy.