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SUMMARY
A study was made of the effects of both systemic and intrauterine progesterone and medroxyprogesterone acetate (MPA) administration on the duration of pregnancy in the guinea-pig. In no case was pregnancy prolonged beyond normal term. When progesterone and MPA were administered to non-pregnant guinea-pigs (in doses up to 50 times that required to block myometrial activity in the rabbit) there was no effect on the amplitude and frequency of intrauterine pressure cycles recorded in vivo by means of intrauterine balloons. The response of the uterus to a standard dose (20 m-u.) of oxytocin was unchanged by progesterone. The administration of progesterone by an intrauterine, instead of a systemic, route did not alter the result. It is concluded that progesterone is not a myometrial blocking agent in the guinea-pig.
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Within some 14 h of treatment with oestradiol benzoate (5 μg), the intra-uterine pressure cycles in ovariectomized puerperal rats were almost abolished. However, treatment with 600 μg actinomycin D 30 min before the administration of oestradiol benzoate interfered significantly with the inhibition of uterine mechanical activity during the following 14 h. 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.
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SUMMARY
Small balloons attached to polyethylene tubing were inserted into either end of one uterine horn in rabbits on about the 22nd day of pregnancy. The tubing was threaded subcutaneously and brought out through an incision at the back of the neck; recordings of intra-uterine pressure changes were made up to and including parturition. There were no pressure changes which could be ascribed to contraction of the myometrium until an average of 31 hr. before delivery of the first foetus but there was considerable variation. Pressure waves recorded from the two balloons were often different in frequency and amplitude and were seldom synchronous. In none of the rabbits did one end of the horn develop 'parturient pressure' before the other and, in general, pressure at the ovarian end of the uterus was higher than at the cervical end. The rabbits could be divided into two groups: (I) those in which the onset of delivery was abrupt and preceding pressure waves were of low amplitude; (II) those in which the pressure waves increased gradually in intensity over several hours before delivery. Both the duration of delivery and the mortality rate of the foetuses were significantly greater in group II than in group I. The results in group I are consistent with the concept that in the normal rabbit parturition is initiated by a release of oxytocin. It is suggested that in group II oxytocin release failed to occur and that this failure was due to 'emotional stress' and possibly circulating adrenaline.
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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 μg) 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 α-adrenergic blocker, phentolamine, nor continuous infusion of the adrenergic β-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 α- or β-adrenoceptor activation.
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SUMMARY
The electrical activity of the myometrium and the intra-uterine pressure were recorded by means of suction electrodes and intraluminal balloons respectively from anaesthetized, oestrogen-primed, ovariectomized guinea-pigs treated with progesterone (25 mg, s.c. twice, 16 h apart). No loss of intra-uterine pressure occurred after progesterone treatment and electrical activities in the balloon-containing and intact horns were indistinguishable. Furthermore, the concentration of progesterone in the uteri of these animals was 0·32 ± 0·05 (S.E.M.) μg (balloon-containing horn) and 0·43 ± 0·06 μ/g wet tissue (intact horn). These values greatly exceed the levels found in uteri of pregnant animals (0·07 ± 0·03 μ/g wet tissue). Thus the failure of progesterone to reduce myometrial activity in the guinea-pig is real and is not due to interference from the balloon, or to failure of the steroid to reach the uterine muscle or to lack of oestrogen priming.
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Relaxin in doses of 5 μg i.v. completely 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 F2α (PGF2α), 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 μg. Relaxin was also ineffective in reducing myometrial activity in similar rats during intra-arterial infusion of PGF2α. It is suggested that the ability of relaxin to inhibit uterine smooth muscle during exogenous stimulation is oestrogen-dependent.
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Porcine relaxin (250 guinea-pig units/mg) infused intravenously into anaesthetized rats at 20 μg/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 μg) was capable of completely suppressing uterine activity driven by prostaglandin F2α infusion in oestrogen-treated ovariectomized rats. Whereas the β-adrenergic blocker, propranolol, had no effect on relaxin-induced inhibition, phentolamine, an α-blocker, significantly delayed the relaxin effect. It is unlikely, however, that relaxin operates through an α-inhibitory receptor. The results show that relaxin acts primarily as a frequency modulator and is capable of antagonizing an exogenous myometrial stimulant.
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ABSTRACT
The rat adrenal cortex contains quantities of dopamine that are compatible with its function as a neurotransmitter, suggesting that locally released dopamine may act as a neuroregulator within the gland. This possibility has been tested by comparing the effects of dopamine on aldosterone secretion in the perfused adrenal with the effects of stimuli designed to provoke the release of intraglandular dopamine.
Infusion of dopamine (0·1–100 μmol/l for 10-min periods) into the isolated perfused rat adrenal gland resulted in a transient, dose-related reduction of aldosterone secretion to a minimum of approximately 50% of the basal value at 1 μmol dopamine/l (ratio of experimental to control measurements, R = 0·53 ± 0·06 (s.e.m.); n = 5). In contrast, dopamine (1–100 μmol/l) had no effect on aldosterone production by dispersed zona glomerulosa cell preparations incubated in vitro.
The effects of changes in K+ concentration (3·9–52 mmol/l) on aldosterone secretion in the perfused gland and dispersed cell preparations were also compared. A similar bell-shaped dose–response relationship was seen in both preparations between 6 and 32 mmol K+/l, with a maximum at 8·4 mmol K+/l and a return to control values with 16, 24 or 32 mmol K+/l. However, infusion of media with very high K+ concentrations (42 or 52 mmol K+/l) reduced the secretion of aldosterone by the perfused gland to approximately 50% of the basal value (R = 0·51 ± 0·05, n = 9; R = 0·49± 0·08, n = 9; respectively) but produced no change in aldosterone production by zona glomerulosa cells. Electrical field stimulation (pulse width 1 ms, 1 Hz at 60 V for 5 min) of the perfused gland also resulted in a reduction in aldosterone secretion (R = 0·66 ± 0·66, n = 6). In the presence of 1 μmol haloperidol/l, a dopamine antagonist, no effect on aldosterone secretion was seen under control conditions, but the responses to 1 μmol dopamine/l, 52 mmol K+/l and field stimulation were eliminated.
The results are consistent with the view that aldosterone secretion by the perfused adrenal gland is subject to an inhibitory dopaminergic control, which may originate from catecholaminergic neurones within the gland itself.
Journal of Endocrinology (1992) 133, 275–282
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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-17β, which was adequate to ensure the survival of 84% of foetuses in ovariectomized pregnant rats. The failure of progesterone to influence myometrial 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-17β in single or repeated doses of from 0·25 to 5 μg, 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.
