A. P. F. Flint

SIGNIFICANT FALL IN PROGESTERONE AND RISE IN ŒSTRADIOL LEVELS IN HUMAN PERIPHERAL PLASMA BEFORE ONSET OF LABOUR

Abstract Plasma progesterone and œstradiol17β levels have been measured serially in thirty-three obstetrically normal young primigravidae from the 20th week of pregnancy up to and during spontaneous labour. Hormones were measured by radioimmunoassay using specific antisera. A significant fall in progesterone and rise in œstradiol occurred during the 5 weeks preceding labour. The plasma progesterone and œstradiol concentrations during labour were no different from those found in the week before labour. These changes are consistent with those found in other species and suggest that the onset of labour in human pregnancy occurs after the withdrawal of an inhibitory effect of progesterone on the myometrium and at a time of relative oestrogen dominance.

Stimulation by oxytocin of prostaglandin F levels in uterine venous effluent in pregnant and puerperal sheep

The purpose of this work was to investigate the effect of oxytocin on prostaglandin F (PGF) concentrations in uterine venous effluent. PGF was measured in utero-ovarian venous plasma from three pregnant ewes and in posterior vena caval plasma from two puerperal ewes, during oxytocin administration. Oxytocin caused 4.9 - 5.3-fold increases in PGF concentrations in the pregnant animals, the response increasing towards term. In the puerperal animals oxytocin caused 3.7 - 17.2-fold increases in PGF concentrations with a marked latency in the response. Measurement of uterine activity and progesterone and total unconjugated oestrogen concentrations indicated that neither uterine contractions nor a decreased uterine blood flow accounted for the elevated PGF levels stimulated by oxytocin.

Plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F during pregnancy in sheep

A specific and sensitive radioimmunoassay is decribed for 13,14-dihydro-15-keto-prostaglandin F in ovine plasma. Using this assay it has been shown that, in sheep, jugular venous 13,14-dihydro-15-keto-prostaglandin F concentrations increase at parturition and correlate well with concentrations of prostaglandin F in the utero-ovarian vein. It is suggested that uterine prostaglandin F production under these conditions may be assessed by measuring peripheral venous 13,14-dihydro-15-keto-prostaglandin F, thereby avoiding the need for chronic utero-ovarian venous catheters.

PROSTAGLANDINS IN THE HUMAN UMBILICAL CIRCULATION AT BIRTH

Prostaglandin E (PGE), prostaglandin F (PGF) and 13, 14‐dihydro‐15‐keto‐prostaglandin F (PGFM) have been measured in umbilical cord plasma obtained immediately after delivery of the baby before clamping of the cord. In general the prostaglandin levels followed the pattern PGFM>PGE>PGF. A significant arterio‐venous difference was demonstrated only for PGE with raised venous levels (P<0.01). In cord blood samples obtained from infants whose mothers had received epidural anaesthesia, no arterio‐venous difference for PGE could be demonstrated although the mean levels were not significantly different from controls. The concentrations of prostaglandins in Umbilical cord plasma proximal to the placenta were found to rise continuously from the time of delivery of the baby with no significant changes after cord clamping or placental delivery. The possible physiological significance of these findings is discussed.

Studies in Menorrhagia: (a) Mefenamic Acid, (b) Endometrial Prostaglandin Concentrations

Twenty‐two women with unexplained heavy menstrual blood loss (average loss for two cycles of >80 ml) were treated with the prostaglandin synthetase inhibitor mefenamic acid during two consecutive menstruations. There was a significant reduction in menstrual blood loss on mefenamic acid therapy, the median loss being 137 ml before treatment and 76 ml while on treatment. Reduction in menstrual loss was achieved in 20 of the 22 patients but varied from a 2% to 78% reduction. The greater the menstrual loss before treatment, the more it was reduced on mefenamic acid therapy. Endometrial concentrations of prostaglandins E2 and F2α in the follicular phase of the cycle were similar whether or not patients had menorrhagia. In the luteal phase, however, 6 of 14 patients with menorrhagia had higher endometrial prostaglandin E2 and F2α concentrations than all 13 controls.

Prostaglandin concentrations in intra-uterine tissues from late-pregnant sheep before and after labour

Prostaglandin E (PGE), prostaglandin F (PGF) and 13,14-dihydro-15-keto-prostaglandin F (PGFM) have been measured in cotyledons and myometrium from sheep before and after labour. Fetal cotyledons contained more PGE than maternal cotyledons which in turn contained more than myometrium. The maternal cotyledon contained the highest concentrations of PGF, but the fetal cotyledon was the only tissue exhibiting a statistically significant rise in the concentration of PGF following labour. Concentrations of PGFM were closely correlated with (although usually lower than) those of PGF.

Progesterone withdrawal: effects on prostaglandins and parturition.

Premature delivery was induced in 1 sheep by injecting the progesterone synthesis inhibitor 2alpha-cyano-44-17alpha-trimethyl-17beta-hydroxyandrost-5-ene-3one (cyanoketone) into the amniotic sac thus separating the effects of progesterone withdrawal and heightened estrogen secretion. The drug was ineffective when infused in 1 ewe intrafetally at 1 mg/24 hours starting 8 days after the placement of catheters on Day 120 of gestation. 10 mg in 16 ml saline intraamniotically repeated 24 hours later induced delivery of twin lambs 19 and 22 hours after the 2nd dose. The lambs weighed 3.5 and 2.66 kg had adrenal weights of 398 and 355 mg suggesting premature delivery. Maternal plasma progesterone levels fell from 45.0 to 6.0 ng/ml in 6 hours and returned to 42.0 ng/ml 14 hours later; prostaglandin F (PGF) rose from .8 to 4.2 ng/ml. At delivery estrogens were 38 pg/ml and progesterone was 45.5 ng/ml normal for that gestational age while PFG was 35.2 normal for ewes at delivery. This is the 1st time delivery was induced by progesterone withdrawal without affecting estrogen in ewes inducing a chronic elevation in plasma PFGs.

PLASMA STEROID CHANGES IN PRE‐TERM LABOUR IN ASSOCIATION WITH SALBUTAMOL INFUSION

Serial measurements of peripheral plasma concentrations of progesterone and oestradiol‐17β were made in 23 women with singleton pregnancies who were given intravenous salbutamol in an attempt to inhibit pre‐term labour. Mean levels of both hormones fell significantly during salbutamol infusion but returned to pre‐treatment levels after therapy was stopped. Plasma human placental lactogen concentrations did not change during salbutamol infusion, suggesting that the fall in steroid hormone levels was unlikely to be an effect of altered uterine or placental blood flow.