PROSTAGLANDINS (PGs) are being used increasingly as abortifacients although their precise mechanism of action is uncertain. One of the compounds frequently used is PGF2α, which has been shown to stimulate the myometrium in vitro1 and in vivo2. Whether or not the direct action of this agent on the uterine muscle alone is responsible for the interruption of pregnancy is not clear, but the long interval between infusion and abortion3 suggests that other mechanisms might be involved; for example, a luteolytic effect4–6. The prompt increase in uterine activity after treatment with prostaglandin, however, argues that the direct effect plays some part in the abortifacient action. Little is known of the influence of other myometrial regulatory agents such as the ovarian steroids on the uterine response to PGs. Accordingly we examined the influence of progesterone on myometrial responses to prostaglandin F2α in the rabbit, a species in which progesterone is known to have a blocking action on the uterine muscle7.
PMID 4999223 4999223 DOI 10.1038/232627a0 10.1038/232627a0
Cite this article
Porter, D. G., & Behrman, H. R. (1971). Prostaglandin-induced myometrial activity inhibited by progesterone. Nature, 232(5313), 627-628. https://doi.org/10.1038/232627a0
Porter, D. G., and H. R. Behrman. "Prostaglandin-induced myometrial activity inhibited by progesterone." Nature, vol. 232, no. 5313, 1971, pp. 627-628.
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-2alpha (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-2alpha (10 microgram/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.
Forty-eight uterine strips were excised from 24 New Zealand white rabbits and studied in vitro. Sixteen strips were examined when eight animals were 25 days pregnant, 24 strips when 12 animals were about 12 hours postpartum, and eight strips about 12 hours after four animals received a single dose of 5 mg. progesterone (P) at spontaneous delivery. When after repeated exposures to electric fields (60 cycles per second, alternating current, of optimum strength, four seconds' duration at intervals of 30 seconds) the approximately 0.5 Gm. strips developed approximately 40-50g wall tension (WT) in steady state, the field strength was reduced in graded steps from 12 v per 5 cm. to 10, 8, 6, 4 and 3 v per 5 cm. and WT recorded. By measuring the effect on WT of "decreasing electric field stimulation" (DEFS), myometrical excitably and threshold were characterized and quantitated. The technique is based on the relationship between the fraction of myometrial cells activated in the total cell population and WT. As the stimulus is decreased in graded steps from optimal to increasingly suboptimal, DEFS activates fewer and fewer cells reflected by the decrease in WT. Threshold is defined by the strength of the minimum electric field which provokes WT and subthreshold by the field strength which fails to excite. Thus fractional WT averages the excitability of cells in the tissue and thus DEFS characterizes this important parameter of uterine function and quantitates threshold under a variety of regulatory conditions. The comparative study of excised uteri in three different endocrine states showed that the regulatory conditions of normal pregnancy (P levels 9 ng. per milliliter) suppressed excitability and increased threshold (to 6 v per 5 cm.). Post partum (P levels 1 ng. per milliliter) excitability increased and threshold decreased (to 4 v per 5 cm.), unless P treatment prevented this characteristic change by suppressing excitability and increasing threshold (to 6 v per 5 cm.). Both regulatory agents, prostaglandin F2alpha (PGF2alpha) and its analogue ICI 81008, increased excitability and decreased threshold significantly in picogram per milliliter concentrations. However, this effect was observed only when the P levels were low. These compounds had little effect, even in manogram per milliliter concentrations, when the P levels were high. The studies also revealed a close relationship between threshold and spontaneous uterine activity. Low threshold promoted while high threshold suppressed spontaneous activity. In similar concentrations the oxytocic actions of PGF2alpha and ICI 81008 were similar but the effect of ICI 81008 was prolonged through strong binding at myometrical sites.
General OB/GYNLipid Metabolism and ImmunityImmunometabolism
Of the 237 women, 92 (38.8%) had experienced both a normal and a toxaemic pregnancy, and 72 (78%) contrasted the sense of well-being associated with a normal pregnancy with the malaise and minor symptoms characteristic of the toxaemic condition. The striking feature of these early minor symptoms of toxaemia was their close resemblance to those of premenstrual syndrome noted in an earlier investigation (Greene and Dalton, 1953), most patients confirming that the minor symptoms during their toxaemic pregnancy were similar, though of increased severity, to those experienced in the premenstruum, irrespective of whether the onset of premenstrual syndrome had preceded or followed the toxaemic pregnancy.