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  • Author: P. W. NATHANIELSZ x
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P. W. NATHANIELSZ

Several amino acids have been shown to stimulate insulin release from the pancreatic β-cell (Fajans, Knopf, Floyd, Power & Conn, 1963; Fajans, Floyd, Knopf & Conn, 1967). Although the various amino acids act directly on the β-cell there is some evidence that in the normal post-prandial state synergism occurs with various alimentary factors (Jarrett, Graver & Cohen, 1969). In this respect amino acids play a similar role to glucose after ingestion of a meal. The rise in both glucose and aminoacid levels stimulates insulin release and the insulin causes an increased uptake of glucose and amino acids by the tissues. In both instances other hormonal and alimentary factors may influence the effect of the metabolite on the β-cell.

There is evidence that the secretion of insulin in response to hyperglycaemia is impaired in the newborn infant (Baird & Farquhar, 1962). Since insulin plays an important role in tissue growth it

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P. W. NATHANIELSZ

Very few sequential studies of plasma thyroxine (T4) levels from birth are available in any species. In human infants, the serum protein-bound iodine (PBI) rises significantly during the first week of neonatal life (Danowski, Johnston, Price, McKelvy, Stevenson & McCluskey, 1951). There then follows a gradual decrease in PBI until by the 6th to 12th week it is below the level at birth. In the calf, the plasma T4 level is elevated in the first 3 hr. of extra-uterine life when it is 12·8 ± 0·6 μg./100 ml. (Nathanielsz, 1969). There then follows a rapid fall in plasma T4 to a level of 4·2 ± 0·6 μg./100 ml. on day 4. A secondary rise occurs with a peak value of 5·7 ± 1·2 μg./100 ml. on day 21. This rise appears to precede the onset of steady growth in the calf which occurs at day 20–25.

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P. W. NATHANIELSZ

SUMMARY

Recently changes in plasma free fatty acids have been suggested as a possible regulator of the levels of free thyroxine in the plasma. Oleic acid has been shown to displace tri-iodothyronine from human serum, human serum albumin, rat serum, rabbit serum and guinea-pig serum. The extent of the displacement, much greater from human serum albumin than from whole serum, suggests that free fatty acid does not affect the globulin binding site. It would also appear that, in the rat, all the binding sites are sensitive to free fatty acids and hence there is probably only albumin binding in this species. The results with rabbit and guinea-pig serum were intermediate to those with human and rat serum. A significant rise in resin uptake of tri-iodothyronine in vitro occurred with an increase of free fatty acid level of 0·5 m-equiv./l., well within the physiological range.

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P. W. NATHANIELSZ and MARGARET ABEL

Glucocorticoids secreted by the foetal adrenal cortex play a major causative role in initiating parturition in the sheep and goat (Liggins, 1968, 1969a; Bassett & Thorburn, 1969; Comline, Nathanielsz, Paisey & Silver, 1970; Thorburn, Nicol, Bassett, Shutt & Cox, 1972). However, Liggins (1969b) failed to precipitate premature parturition with dexamethasone (4 mg/h) infused into the maternal circulation of the pregnant ewe. Fylling (1971) produced delivery with 6–10 mg dexamethasone/day in the pregnant ewe. Since it is uncertain what role glucocorticoids may play in polytocous species, an attempt was made to initiate parturition by infusing cortisol into the maternal circulation of the pregnant rabbit. Cortisol was chosen as the glucocorticoid for infusion since in the newborn rabbit the plasma cortisol: corticosterone ratio is about 3·0 (K. W. Malinowska, R. N. Hardy & P. W. Nathanielsz, unpublished observations).

Pregnant rabbits of known gestational age were anaesthetized with sodium pentobarbitone (30–45

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P. W. NATHANIELSZ and MARGARET ABEL

SUMMARY

Continuous infusion of cortisol at rates from 0·31 to 1·24 mg/h into pregnant rabbits from day 21 of pregnancy onwards induced delivery in approximately 72 h. Similar rates of infusion into the foetal amniotic sac induced delivery with a shorter latency. Maternal infusion of 1·24 mg cortisol/h produced parturition providing it was continued for at least 24 h. If after this period the infusion was terminated, delivery still occurred after a further 48 h (i.e. 72 h in all). Progesterone administration to the mother blocked the effect of cortisol administered by the maternal or foetal route.

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J. W. BUCKLE and P. W. NATHANIELSZ

SUMMARY

Prostaglandin F2α (PGF2α) was infused intra-aortically at different rates into rats for 11·5 h from day 18 of gestation. At doses in excess of 5 μg/h premature delivery invariably occurred 40–41 h later. At lower doses an all-or-none effect was observed, some animals delivering prematurely and others continuing to term. Parturition could not be induced earlier than 40 h after the start of the treatment even by a continuous infusion of PGF2α, suggesting that the luteolytic role of PGF2α is more important than its oxytocic action in this case.

The rate of fall in plasma progesterone was greater in the rats delivering prematurely than those delivering at term, although the final concentrations of between 15 and 30 ng/ml at delivery were the same.

Labour appeared more normal in the animals receiving PGF2α than in those which had been bilaterally ovariectomized. The possible significance of this in relation to an effect of PGF2α on oestrogen secretion is discussed.

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J. W. BUCKLE and P. W. NATHANIELSZ

SUMMARY

Myometrial activity was recorded in vivo in unrestrained pregnant rats from day 19 of gestation using radiotelemetry. The effects of short-term infusions of theophylline, dibutyryl cyclic AMP and 8-bromo-cyclic GMP were investigated. All three compounds caused a decrease in oxytocin-induced, prostaglandin F-induced and spontaneous uterine activity. After cessation of the infusion of these compounds uterine activity returned to near pre-infusion levels within approximately 15 min in most animals. The possible roles of cyclic nucleotides in the control of myometrial contraction are discussed in the light of these observations.

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P. M. B. JACK and P. W. NATHANIELSZ

A preparation has been described previously for the investigation of the action of various agents on the myometrium of the pregnant rabbit. This technique involves the insertion of specially prepared catheters into the femoral artery and vein under sodium pentobarbitone (Nembutal) anaesthesia. The catheters are passed cranially until the tips lie well above the level of origin of the ovarian arteries and veins. At the same time a pressure-sensitive radiotransducer is inserted into the uterus to record intrauterine pressure changes (Smith, Abel & Nathanielsz, 1973).

The experiments reported here were performed on animals catheterized at day 21 of pregnancy and infused with 1 μg prostaglandin F (PGF through the aortic catheter for 16 h after recovery from anaesthesia. The PGF infusion was then stopped and the catheters were maintained patent with heparinized saline between experiments. This procedure resulted in the gradual evolution of spontaneous myometrial activity and

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R. B. PAISEY and P. W. NATHANIELSZ

Plasma cortisol levels are raised in the cord blood of newborn human infants (Migeon, Prystowsky, Grumbach & Byron, 1956). In man these high levels have been attributed to placental permeability to the high maternal levels of cortisol which occur during parturition. In the pregnant sheep the placenta does not appear to be permeable to cortisol in the latter stages of gestation since variations in maternal cortisol levels are not reflected in changes in the level of cortisol in the foetal blood (Bassett & Thorburn, 1969). Few observations have been made in this species of any changes in placental permeability to cortisol that may occur during parturition. Studies with radioactive cortisol suggest that there is little, if any, increase in the passage of cortisol across the placenta in either direction during parturition (Beitins, Kowarski, Shermeta, De Lemos & Migeon, 1970; Comline, Nathanielsz, Paisey & Silver, 1970).

The hypothalamo—adenohypophysial—adrenocortical system is active

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P. W. NATHANIELSZ, MARGARET ABEL and G. W. SMITH

Prostaglandin F (PGF) has been shown to possess luteolytic properties in several species including the rabbit (Duncan & Pharriss, 1970; O'Grady, Kohorn, Glass, Caldwell, Brock & Speroff, 1972). Surgical removal of the corpus luteum leads to parturition in the rabbit. Thus, PGF should initiate parturition in this species. In primates, controversy has arisen over the ability of PGF to produce luteolysis (Kirton, Pharriss & Forbes, 1970). Since prostaglandins are very rapidly cleared by the pulmonary circulation, observed discrepancies may be due to the actual route of administration and dosage used.

Experiments have been carried out to measure the effect of PGF in producing parturition in the pregnant rabbit. PGF was infused continuously into rabbits with an indwelling aortic catheter (Nathanielsz & Abel, 1972). Infusions were started on day 21 and continued until delivery. PGF was infused at dose rates varying from 1·125 ng/h