H.G. Britton

Maternal and Fetal Arginine Vasopressin in the Chronically Catheterised Sheep

Catheters were implanted into the fetal dorsalis pedis and maternal jugular veins of 6 ewes of 122–130 days gestation age. Fetal plasma arginine vasopressin (AVP) concentrations rose in the last few days before parturition from undetectable levels to values associated with response to minor stress. Similarly, AVP was frequently present in maternal plasma in the last week of gestation but was rarely detected earlier. The levels attained in the mother were somewhat lower than in the fetus.

Pituitary and Plasma Concentrations of Adrenocorticotrophin, Growth Hormone, Vasopressin and Oxytocin in Fetal and Maternal Sheep during the Latter Half of Gestation and the Response to Haemorrhage

Fetal haemorrhage in exteriorized fetuses of 90 to 143 days conceptual age caused marked increases in fetal plasma ACTH and AVP with maximal values for ACTH at about 40% blood loss and maximal values

25-Hydroxycholecalciferol 1α-Hydroxylase Activity in the Kidney of the Fetal, Neonatal and Adult Guinea Pig

Homogenates of fetal, newborn and maternal kidney and placenta have been compared with homogenates of non-pregnant adult kidney for their ability to hydroxylate 25-hydroxycholecalciferol. The activity in the fetal kidney near term is similar to that in the mother and 4--5 times that in the non-pregnant adult. These differences from the non-pregnant adult are significant (p less than 0.05 and 0.1 fetus and newborn, respectively). Even higher levels are present in some newborn 12--24 h after birth, but these values fall towards the non-pregnant level in the following 21 days. Significant hydroxylating activity is present in the near-term placenta.

Maintenance of sheep fetuses by an extracorporeal circuit for periods up to 24 hours

Abstract The results obtained on two sheep fetuses maintained for 24 hours on an artificial perfusion circuit (artificial placenta) with the umbilical vessels are described. The problems involved in the maintenance of such isolated fetuses for prolonged periods on extracorporeal circuits are discussed.

Antidiuretic Hormone and Oxytocin Release and Antidiuretic Hormone Turnover in the Fetus, Lamb and Ewe

The release of antidiuretic hormone in response to the introduction of an osmotic stimulus into the cerebral circulation of the fetal sheep and lamb is described. Infusion of 1.0 M

Activation of carbamoyl phosphate synthetase by cryoprotectants

SummaryCarbamoyl phosphate synthetase I (E.C.6.3.4.16) from rat liver is activated by a range of cryoprotectants. Their diverse chemical structure and the normal stoichiometry and pattern of positional isotopic exchange for the reaction catalyzed in their presence strongly supports an allosteric mechanism for activation by the physiological activator, acetylglutamate, and by the cryoprotectants. Activation appears not to require any specific group in the cryoprotectants, but different agents activate to different degrees. All cryoprotectants found to activate are good hydrogen-bond formers and have low molecular weight (<1 000 for polyethylene glycols). This suggests that the cryoprotectant must associate with the enzyme to activate. In the presence of acetylglutamate all cryoprotectants tested, irrespective of their capacity to activate, inhibit.Carbamoyl phosphate synthetase I has activity in the absence of cryoprotectants and acetylglutamate. Under these conditions the Kms for ATP and K+ are very high, the Km for NH4+ is very low, the Vmax appears not to exceed 15% of that at saturation of acetylglutamate and the ratio of ATPase to carbamoyl phosphate synthetase activity is ca. three times that of the acetylglutamate activated enzyme. Acetylglutamate lowers the Kms for ATP and K+, and increases the Km for NH4+ and the Vmax. From steady state kinetics, pulse-chase, and measurements of the rate of activation, an allosteric model for activation of the enzyme by acetylglutamate is proposed in which there are two active species, R and R - AG (AG = acetylglutamate), which have similar but not identical activities. One molecule of ATP binds with high affinity to active and inactive enzyme species, but K+ and the other molecule of ATP bind preferentially to the active species.In the absence of acetylglutamate, glycerol (an effective activator) reduces the Kms for ATP and K+, increases the Vmax, and dramatically reduces the S0.5 for acetylglutamate to <1 μM for the synthetase reaction. In the presence of excess acetylglutamate, glycerol markedly reduces the Km for ATP for the synthetase, decreases the Vmax, NH4+ becomes a more effective activator than K+, and Na+ activates appreciably. From these and other kinetic measurements on the ATPase activity, the partial reverse reaction and rates of activation, and from pulse chase observations, the effect of glycerol is rationalized in terms of the allosteric model proposed for the actions of acetylglutamate if: a) glycerol reduces the rate of transformation and alters the allosteric equilibria between active and inactive enzyme species, and b) glycerol inhibits the active enzyme, at least in part due to slower conformational changes associated with dissociation of the products and binding of substrates.Glycerol also activates carbamoyl phosphate synthetase from E. coli in the absence of ornithine. This and the above findings are compared with data on the actions of cryoprotectants on carbamoyl phosphate synthetase II (EC 6.3.5.5) from rat liver. There are considerable similarities in the actions of these agents on the three enzymes. The relationship between these findings and the actions of cryoprotectants on other enzymes and possible physiological implications are discussed.

Glucagon Release in the Sheep Fetus

Arginine administered to the fetal sheep elicits a brisk transient increase in the glucagon concentration of peripheral fetal plasma. Neither direct elevation of the fetal plasma glucose level nor the

Corticotrophin and cortisol concentrations in the plasma of the chronically catheterised sheep fetus.

Plasma from six chronically catheterised sheep fetuses of 113–126 days conceptual age showed high levels of corticotrophin at all ages with somewhat higher values towards term. Plasma cortisol was not clearly related to corticotrophin in individual samples but was highly correlated in the pooled data. Short bouts of hypoxia (5–10 min 10% O2 in N2 to the mother) produced no significant change in either corticotrophin or cortisol although small transient changes in PO2 and lactate occurred. The high levels of corticotrophin suggest that the possibility of stress in the chronically catheterised preparation must be considered.

Impermeability of the Sheep Placenta to Glucagon

The permeability of the placenta to glucagon was studied in sheep of gestational ages of 99–143 days. Administration of large doses of glucagon to the mother was associated with little or no change in

Insulin Secretion in the Fetal and Neonatal Sheep

The effect on plasma insulin of elevating plasma glucose levels was studied in exteriorized sheep fetuses of 68 to 142 days conceptual age and in 2 lambs, 1 and 7 days old. Fetuses of less than 110 da