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SUMMARY
Some derivatives of phenelzine have been shown to interrupt pregnancy in mice, when given after implantation, i.e. on days 7–10. Pregnancy can be maintained in mice treated with these compounds and in mice hypophysectomized on day 7 by administration of suspensions of whole mouse pituitaries, of human chorionic gonadotrophin or of progesterone given with a basic concentration of oestrogen. Prolactin was ineffective in maintaining pregnancy. The action of the phenelzine derivatives could also be reversed by 0·5–1 μg. luteinizing hormone and by 0·05 μg. oestradiol. The compounds antagonized the action of progesterone in maintaining pregnancy in ovariectomized mice and this indicates that they act on the uterus. There may be, in addition, a more central action, e.g. on the ovary or on the pituitary but this would be masked by the peripheral (i.e. uterine) effect.
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University of Melbourne, Department of Medicine, Austin Hospital, Heidelberg, Victoria 3084 and Monash University, Department of Medicine, Prince Henry's Hospital, St Kilda Road, Melbourne, Victoria 3004, Australia
(Received 25 February 1974)
The present studies were made on the function of the placenta and foetal adrenals in an oophorectomized and adrenalectomized woman during the second trimester of pregnancy. Bilateral oophorectomy at week 9 of pregnancy and bilateral adrenalectomy at week 14 of pregnancy were carried out for multiple breast cancer metastases. Unfortunately, at the time, the possibility of pregnancy was not excluded. Replacement treatment was started and continued with cortisol (20 mg/day).
Oestrone, oestradiol and oestriol were measured by the method of Brown (1955) and colorimetrie estimation and correction for loss were done as previously described (Maeyama, Nakagawa, Tuchida & Matuoka, 1969). Pregnanediol was measured by g.l.c. Urinary 17-hydroxycorticosteroids (17-OHCS) were measured by a modification of the method of Silber &
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Neurohypophysial hormones are thought to be involved in alterations in fluid balance during pregnancy and delivery. In the course of normal pregnancy intravascular volume is increased whereas sodium restriction is thought to reduce plasma volume and cardiac output. In the present study, we measured the effect of long-term severe sodium restriction on vasopressin (AVP) and oxytocin (OT) levels during normal pregnancy and after delivery.
Fifty-nine healthy nulliparous women were randomized either for a low sodium diet (20 mmol sodium daily) or for a normal diet from week 12 of pregnancy onwards. Circulating plasma levels and urinary excretion of AVP and OT, their neurophysins (Np-AVP and Np-OT) and AVP bound to platelets were determined at regular intervals during pregnancy and after delivery. After completion of the study, women on a sodium-restricted diet were compared with control women on a normal diet using repeated measurement ANOVA with adjustment for potentially confounding variables.
After randomization, a reduction in urinary sodium excretion of, on average, 40–82% was found. In general, no effect of sodium restriction could be demonstrated on the various parameters (0·53<P<0·98) with the exception of a significantly lower 24-h urinary AVP excretion by non-smokers with sodium restriction compared with non-smokers having a normal diet (P=0·018) For all parameters, clear changes were found in the course of pregnancy and puerperium (P<0·0001 to P<0·005). Platelet-bound AVP decreased and Np-OT increased during pregnancy. After birth, free plasma AVP, plateletbound AVP, OT, osmolality, sodium and potassium increased, while Np-AVP and Np-OT decreased.
Although elevated Np-AVP and Np-OT levels during pregnancy seem to indicate increased release of neurohypophysial hormones, pregnancy up to 36 weeks of gestation is accompanied by low circulating AVP and OT levels.
Long-term severe sodium restriction diminishes urinary AVP excretion in (non-smoking) pregnant women, without changing circulating levels of AVP and OT, despite the known reduction in circulating volume. The reduced circulating (platelet-bound) AVP levels during pregnancy, whether or not in combination with severe sodium restriction, support the absence of significant non-osmotic stimulation of AVP during pregnancy.
Journal of Endocrinology (1997) 152, 345–354
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SUMMARY
The haemagglutination-inhibition test was investigated as an immunological method for the assay of human chorionic gonadotrophin (HCG). The preparation of a potent antiserum to HCG is described. The results of the assay of HCG during normal pregnancy in ten patients are compared with the results of immunological assays from two Swedish laboratories. The mean values and the 95 % confidence limits for the excretion of HCG from the 10th week of normal pregnancy are calculated.
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SUMMARY
Progesterone or progestin concentrations were measured in the peripheral plasma of the tammar wallaby (Macropus eugenii) during pregnancy and the oestrous cycle, using a competitive protein-binding method. In common with most other members of the marsupial family Macropodidae, the tammar has a gestation period slightly shorter than one oestrous cycle, and the occurrence of pregnancy does not affect the time of onset of the following oestrus. This study was an attempt to obtain direct evidence for the common assumption that most macropodid marsupials secrete the same amounts of ovarian hormones during pregnancy as they do during the oestrous cycle. The effect on progesterone levels of ovariectomy and removal of the corpus luteum was also studied to discover whether an extra-ovarian source of progesterone exists during pregnancy. Circulating levels of both total plasma progestins and progesterone are very low compared with other mammalian species—less than 1 ng/ml at all stages of the reproductive cycle. An increase in plasma progesterone concentration, apparently of ovarian origin, occurs before birth and/or oestrus, and this may possibly be associated with parturition. The plasma progestin concentration during pregnancy, and that of progesterone during the last 10 days of pregnancy, were significantly greater than during the oestrous cycle.
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Concentrations of prostaglandin F2α (PGF2α) and prostaglandin E (PGE) were measured in endometrium from 18 women with ectopic pregnancies. In the nine pregnancies not associated with vaginal bleeding or an intra-uterine contraceptive device (IUCD; intact ectopics), concentrations of PGF2α (12·8 ± 7·4 (s.e.m.) ng/g) and PGE (4·7 ± 3·0 ng/g) were similar to those in decidua from nine intra-uterine pregnancies of comparable gestational age (14·4 ± 4·4 and 8·2 ± 2·2 ng/g respectively). In both ectopic and intra-uterine pregnancies concentrations of prostaglandins were significantly lower than those found in endometrium throughout the normal menstrual cycle (P < 0·01). In nine ectopic pregnancies with associated vaginal bleeding and/or an IUCD, concentrations of PGF2α and PGE were significantly higher than in the intact group (P < 0·05), although the concentration of PGF2α remained significantly lower than levels in normal secretory endometrium (P < 0·05).
These results suggested that suppression of endometrial synthesis of prostaglandin during early pregnancy may be mediated systemically rather than through a local action of the conceptus.
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The concentration of progesterone in the peripheral plasma of seven sheep during late pregnancy was reduced by injection of an inhibitor of 3β-hydroxysteroid dehydrogenase activity. Concentrations of progesterone were 10·0± 1·0(s.e.m.) ng/ml (n = 6) before injection of the inhibitor, fell to 1·39 ± 0·40 ng/ml (n = 6) 30 min after injection, and remained within this lowered range for 6 h after injection. By 20–24 h and 30–35 h after injection progesterone concentrations had recovered to 4·63±0·94 and 14·07 ±4·17 ng/ml respectively (n = 6). Six out of seven ewes delivered prematurely 32·5± 2·9 h after injection. Delivery appeared to be normal, and was associated with increasing concentrations of 13,14-dihydro-15-oxo prostaglandin F2α in peripheral plasma. Concentrations of oestradiol-17β17β in peripheral plasma were slightly raised immediately before delivery, at which time progesterone concentrations were within the preinjection range. These data suggest that progesterone withdrawal is one mechanism that initiates increased prostaglandin F2α secretion in the pregnant sheep.
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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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Several 9α-halogenated progestagens are of high biological activity in the ewe. Cronolone (9α-fluoro-11β-hydroxy-17α-acetoxyprogesterone), SC-21110 (9α-chloro-11β-hydroxy-17α-acetoxyprogesterone and SC-5848 (9α-chloro-11β-hydroxyprogesterone) are indistinguishable from progesterone in priming the spayed ewe to respond to oestrogen and moreover are 20 times as potent as progesterone in this bioassay (Shelton, Robinson & Holst, 1967; Holst & Moore, 1968; R. Sinclair, personal communication). Cronolone has a similar potency in the inhibition of oestrus (Shelton & Robinson, 1967), and in a flock of ewes allows precise synchronization of oestrus and ovulation after termination of treatment (Robinson, Moore, Holst & Smith, 1967). These findings indicate that 9α-halogenated progestagens are similar to progesterone in duration of activity and are of high potency. To study further the biological activity of these compounds, they were tested for ability to maintain pregnancy in rats.
Virgin female rats weighing 200–250 g. were housed in a constant temperature environment with free access to food and
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(eNOS) and prostanoid production in response to cytosolic phospholipase A2 activation are thought to be mediated by Ca 2+ signaling. Pregnancy is a time of increasing needs and demands by the growing fetus and these are met in part by
