SUMMARY1. The blood flow to the liver in fetuses near term, newborn and adult sheep was measured by the Fick principle, using radionuclide-labelled plastic microspheres, before and during infusion of adrenaline, noradrenaline or glucagon.2. Glucose output and lactate consumption by the liver in sheep of each age group were calculated by application of the Fick principle using the concentration gradients of these metabolites measured in blood samples obtained, simultaneously with blood flow measurements, from catheters chronically implanted in the inflow and outflow vessels of the liver.3. Catecholamines were infused into the portal vein of fetuses near term at a rate comparable with that at which they are known to be secreted in the sheep fetus during moderate to severe hypoxia. The cardiovascular and metabolic responses to these infusions were found to be comparable with those that occur in the fetus during hypoxia.4. Catecholamines increased glucose output from the liver in all except the immediate post-partum animals. Catecholamines were less effective than glucagon in promoting glucose release. The mean increments in glucose output during adrenaline infusion were 0055+0-015 mmol min-(100 g liver)-1 in the fetus, 0-122+ 0024 mmol min-(100 g)-1 in the 2-week-old lambs, 0078+0019 mmol min-' (100 g)-' in young lambs and 0-049+0-012 mmol min-' (100 g)-' in the adult sheep.During glucagon infusion the mean glucose output increments were 0-146 + 0023 mmol min-1 (100 g)-in the fetus, 0-274+0-085 mmol min-(100 g)-1 in the 2-week-old and young lambs and 0 180+0-054 mmol min-' (100 g)-1 in the adult. Adrenaline was more potent than noradrenaline, suggesting that the major glycogenolytic response might be f-receptor mediated.5. In the immediate newborn period the output of glucose from the liver was high (0-20 + 0-05 mmol min-' (100 g liver)-' and was not statistically significantly increased by infusion either of glucagon or of catecholamines which resulted in similar increments of glucose output of about 04128 +0-133 mmol min-' (100 g)-1. It is probable that the high output of glucose reflected the high endogenous circulating levels of catecholamines and glucagon in these animals at birth and that further infusions failed to add significantly to the already near-maximal glucose release. R. S. K. APATU AND R. J. BARNES absence of high levels of circulating catecholamines and glucagon in the resting fetus but also may indicate a deficiency in either the receptor mechanism for catecholamines or of the intracellular second messenger system for glycogenolysis. The greater effectiveness of glucagon (than adrenaline) as a mediator of glucose release in these animals tends to support the idea of a fl-receptor rather than a second messenger deficiency. It is postulated that a deficiency of hepatic ,-adrenergic receptors, provided that it can be corrected in time for birth, would help to protect glycogen stores in the liver in utero.

SUMMARYIn the present study, the ontogenic changes in gluconeogenic enzyme activities and in hepatic glycogen and ,-adrenergic receptor levels were investigated in fetal pigs from 70 days of gestation until delivery at term (114 + 2 days). The values were compared with those observed in fetuses infused subcutaneously with cortisol for 6 days beginning at 82-84 or 92-94 days of gestation. Tissue glucose-6-phosphatase (G6Pase) activity increased with increasing gestational age in the liver, kidney and duodenum of control fetal pigs. At birth, there was a further increase in G6Pase activity in the liver but not in the kidney or duodenum. In the kidney, there was a similar gestational increase in phosphoenolpyruvate carboxykinase (PEPCK) activity. These changes in enzyme activities closely paralleled the prepartum increase in fetal plasma cortisol and were accompanied by increases in hepatic glycogen content and f-adrenergic receptor density. At 98-100 days, there were significant increases in G6Pase activity in the liver, kidney and duodenum of the cortisol-infused fetuses, whereas at 88-90 days only renal G6Pase was significantly elevated by cortisol infusion. Cortisol infusion also increased hepatic ,-receptor density at 88-90 days and hepatic glycogen content at both gestational ages. There were no changes in hepatic PEPCK, hepatic or renal fructose diphosphatase and aspartate amino transferase activities during cortisol infusion or with increasing gestational age. When the data from all the piglets were combined, irrespective of age or treatment, there were significant positive correlations between log plasma cortisol and G6Pase activity in the liver, kidney and duodenum. Similar positive correlations were observed between hepatic ,/-adrenoceptor density and log plasma cortisol and between the latter values and the hepatic glycogen content. These findings show that cortisol induces tissue G6Pase activity in the fetal pig and suggest that the prepartum rise in endogenous cortisol may be responsible for the increase in fetal glucogenic capacity observed towards term in this as in other species.

1. The blood flow to the liver in fetuses near to term, in newborn and in adult sheep was measured in vivo by the Fick principle using radionuclide‐labelled plastic microspheres and timed withdrawal of reference organ blood samples. 2. There is a rapid flow of blood, 410.1 +/‐ 41.8 ml min‐1 (100 g liver)‐1, mean +/‐ S.E.M., to the liver in the fetus. Immediately after birth the blood flow is significantly less (172.5 +/‐ 27.5 ml min‐1 (100 g liver)‐1), reflecting the loss of the umbilical venous return to the liver following delivery and separation from the placenta. Arterial blood flow to the liver per unit weight of liver was small in the fetus (9.5 +/‐ 1.2 ml min‐1 (100 g liver)‐1), significantly greater in the immediate newborn (27.9 +/‐ 7.9 ml min‐1 (100 g)‐1) but appeared to decline with age after birth to 12.2 +/‐ 6.6 ml min‐1 (100 g)‐1 in lambs at 16 weeks of age. Portal blood flow to the liver, on a weight basis, changed little with age being 126 +/‐ 20.9 ml min‐1 (100 g liver)‐1 in the fetus, 144.7 +/‐ 21.1 ml min‐1 (100 g liver)‐1 in the immediate newborn and 203.2 +/‐ 27.8 ml min‐1 (100 g liver)‐1 in the adult. 3. Oxygen consumption and glucose and lactate fluxes across the sheep liver were determined from 132 days of gestation into adulthood. 4. The oxygen consumption by the fetal liver was 0.11 +/‐ 0.02 mmol min‐1 (100 g)‐1 which represents about 6% of the total fetal oxygen metabolism. Immediately after birth there was an apparent increase in liver oxygen consumption but the wide variation in the values recorded means that the change is not statistically significant. There were no significant changes in liver oxygen consumption with age after delivery, oxygen consumption by the adult liver was 0.16 +/‐ 0.05 mmol min‐1 (100 g)‐1. 5. The liver at all ages studied consumed lactate. Lactate consumption was particularly high in the fetus (0.13 +/‐ 0.04 mmol min‐1 (100 g)‐1 and could account for three times the oxygen consumed by the fetal liver, but the fate of this lactate is not yet known. 6. In the fetus the liver is in approximately zero glucose balance; in contrast postnatal animals release glucose from the liver at rest.(ABSTRACT TRUNCATED AT 400 WORDS)

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