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The concentration of cortisol and cortisone in mixed saliva has been measured in normal non-pregnant women, normal pregnant women in the third trimester of pregnancy and pregnant ones with mild toxaemia in the third trimester. The ratio of cortisol to cortisone was 1:4 for the non-pregnant and 1:5 for the pregnant women. The mean concentration of cortisol for the pregnant subjects was twice that of the non-pregnant and the mean concentration of cortisone three times that of the non-pregnant women. Filtration studies showed no significant binding of cortisol or cortisone in the saliva.

It is concluded that the raised concentration of cortisol and cortisone in saliva indicates a raised concentration in the cells of the salivary gland. If this rise is common to the connective tissues generally it provides a reasonable explanation for the remission of rheumatoid arthritis experienced by some patients in the latter months of pregnancy.

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1. Samples of plasma and serum from healthy non-pregnant women, from normal gravidae and from patients with pre-eclamptic toxaemia have been tested for antidiuretic activity by means of the method described by Jeffers, Livezey & Austin [1942].

2. An antidiuretic substance (ADS) is present in normal pregnancy serum, and in pre-eclamptic plasma and serum. ADS was not detected in non-pregnant serum or plasma or in normal pregnancy plasma.

3. Normal pregnancy plasma contains a substance which inactivates both vasopressin and the ADS present in normal pregnancy serum and in pre-eclamptic plasma. This inactivator was not demonstrated in non-pregnant plasma.

4. Vasopressin and ADS are inactivated both by thioglycollic acid and normal pregnancy plasma.

5. The antidiuretic activity of normal pregnancy serum is not attributable to 5-hydroxytryptamine (5-HT).

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Rabbits were injected with oestradiol-17β for 3–6 consecutive days at different times during pregnancy. The course of pregnancy was followed thereafter, or, in acute experiments, the staircase effect and the oxytocin sensitivity were determined on the day following the last injection. Results showed that doses of oestrogen sufficient to interrupt pregnancy through an effect on the endometrial component of the uterus did not directly antagonize the influence of endogenous progesterone on the myometrium. Diminution of the progesterone block indicated by the oxytocin sensitivity of the myometrium is considered to be due to degeneration of the placenta and hence of its ability to maintain the corpus luteum.

The dosage of oestrogen necessary to interrupt pregnancy was higher in late pregnancy. This is in agreement with the finding that oestrogen production increases steadily from mid-pregnancy to term.

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Stimulation of the nipple lines and genital and pelvic regions by self-licking, found previously to increase during pregnancy in the rat, was studied for its effect on mammary gland development. Licking was prevented by fitting wide rubber collars around the necks of rats for the entire period of pregnancy or for either the first half (days 1–12) or the second half (days 12–22) of pregnancy. The percentage of secretory tissue, and ratings of lobulo-alveolar (L-A) development and secretory (S) activity were used to measure the development of the gland on either the 22nd or the 12th day of pregnancy. Notched collars, which permitted licking, were used as a control for any stress effects that resulted from the collars, and injections of formalin were used as a control for any stress produced by the collar. Mammary development was reduced to only 50% of normal, and L-A development and S-activity ratings showed a corresponding retarded development in animals wearing a collar throughout pregnancy. Notched collars did not affect gland development and formalin injections accelerated it. There was no difference in the effects of wearing a collar during the first or second half of pregnancy: both groups were equal in gland development on the 22nd day and their glands were more developed than those of females wearing a collar throughout pregnancy. In animals that wore collars from the beginning of pregnancy, gland development was already retarded (28%) by mid-pregnancy. Rats whose glands were reduced in development during the first half of pregnancy showed less nipple-line licking during the second half of pregnancy. These findings indicate that stimulation provided by self-licking contributes significantly to mammary gland development during pregnancy and, therefore, the activity of the gland before parturition, like lactation post partum, is regulated in part by external stimulation.

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R Magnaterra, O Porzio, F Piemonte, A Bertoli, G Sesti, D Lauro, LN Marlier, G Federici, and P Borboni

Pregnancy is associated with adaptive changes including increased number and size of beta cells and enhanced gap-junctional coupling among beta cells, increased glucose-induced insulin response and decreased glucose stimulation threshold. The role exerted by pregnancy steroids and lactogenic hormones in the development of islets upregulation during pregnancy has been widely investigated. In the present study we studied the possibility that pregnancy steroids induce functional modifications of beta cells involving the expression and function of glucokinase. Our results indicate that estradiol and progesterone do not influence significantly glucokinase mRNA expression, while they induce a dose-dependent and time-dependent increase of glucokinase activity in RIN 1046-38 cells. The increased enzymatic activity results in an increased glucose-induced insulin release. Therefore it is possible to hypothesize that pregnancy steroids influence glucokinase expression in beta cells at a post-transcriptional level and that this effect contributes to the development of hyperinsulinemia during pregnancy.

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Anthony J Weinhaus, Laurence E Stout, Nicholas V Bhagroo, T Clark Brelje, and Robert L Sorenson

Introduction To accommodate the increased demand for insulin during pregnancy, pancreatic islets of Langerhans undergo structural and functional changes leading to increased insulin release under normal glucose homeostasis ( Parsons

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During normal human pregnancy alterations in liver function similar to those seen in cholestasis occur (Tindall & Beazley, 1965; Haemmerli & Wyss, 1967). Adlercreutz & Tenhunen (1970) concluded that oestrogens were primarily responsible for this effect. In a previous report from this laboratory (Tikkanen, 1972) progressive changes, including decreasing proportions of OE3-3Gl† and increasing proportions of OE3-3S,16Gl†, in the urinary excretion of oestriol conjugates during pregnancy were noted, which were regarded as reflections of changes in the excretory function of the liver. Since a clear consistent change in urinary oestriol conjugate pattern was not observed in all the pregnancies studied, it appears that some women are more susceptible than others to this action of oestrogens on liver function. In multiple pregnancies Beazley & Tindall (1966) noted changes in the excretory function of the liver that were similar to but greater than those previously observed in singleton pregnancies. Accordingly, it might

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Reports on the fertility rate and the outcome of pregnancy in alloxan diabetic rats are conflicting. In part this is due to the differing conditions of the experiments, some authors having induced diabetes before pregnancy [Davis, Fugo & Lawrence, 1947], others after conception [Miller, 1947]. In general, observations have been limited to animals which had only recently been made diabetic, and, as such, are open to the objection that alloxan diabetes in its early stages may fluctuate markedly in severity. It therefore seemed of importance to study female rats with long-standing diabetes, particularly in respect to fertility rate and outcome of pregnancy. Human diabetic pregnancy results in delivery of large babies and a high late foetal and neonatal mortality. The outcome of pregnancy in the alloxan diabetic animal has therefore been studied particularly from these two aspects. The problem of high foetal loss has already been the subject of discussion

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The plasma 17:21-dihydroxy-20-keto-corticosteroid levels in the cow in late pregnancy (33–0 days before calving) are only slightly higher than in the cow soon after calving (0–99 days). A larger rise was sometimes seen in the last few days before calving.

Except in one case where calving was difficult, no evidence of increased levels associated with the time of labour was found.

Higher levels in the first day or two after calving were seen in some cases, but subsequently levels were uniformly low—the difference from earlier levels being statistically significant (P=0·01).

In general, these results are in contrast with the human picture. Possible reasons for these findings are discussed.

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1. The fertility and outcome of pregnancy have been studied in alloxan diabetic rats treated with insulin. The diabetes was only partly controlled, but the general condition of the diabetic mothers was good.

2. Fertility rate was increased compared with that in animals in which the diabetes was not treated with insulin. Stillbirth rate and neonatal death rate (5% combined loss) and the percentage of weaned animals (89%) were normal, as contrasted with a 37% combined stillbirth and neonatal mortality rate and 50% death-rate before weaning in the offspring of untreated diabetic mothers.

3. It is concluded that alloxan diabetes does not adversely affect the foetal mortality, neonatal death-rate or the feeding of young animals unless it impairs the general health of the mother.