Fetal and maternal hormonal response to starvation in the ewe.

Abstract

Summary: Five ewes 90–130 days of gestation with chronically indwelling fetal catheters were studied. Blood samples were drawn each morning simultaneously from the maternal femoral artery, fetal femoral artery, and fetal umbilical vein. Total starvation was begun after blood samples had been drawn on the 3rd morning, but water was given ad libitum. The mean maternal arterial plasma glucose concentration before starvation (73.4 ± 31.0 (SEM) mg/100 ml plasma H2O) fell to 54.8 ± 5.2 mg/100 ml (P < 0.01) after 24 hr of fasting and to 37.5 ± 1.6 mg/100 ml (P < 0.001) by 72 hr of fasting. The maternal arterial fructose concentration was low in both the fed (2.9 ± 0.4 mg/100 ml) and fasted states (1.8 ± 0.5 mg/100 ml, day 3). The maternal arterial insulin concentration fell early in fasting from a mean of 27.9 ± 3.9 uU/ml on 2 days before starvation to 12.4 ± 1.8 uU/ml after 24 hr of fasting (P < 0.005) and remained low for the duration of the 7-day fasting period. The mean maternal arterial glucagon concentration in the fed state was 112 ± 20 pg/ml and did not change significantly throughout the 7 days of maternal fasting. Fetal arterial plasma glucose was much lower than maternal levels (mean 18.4 ± 1.1 mg/100 ml plasma H2O in the fed state), decreased to 12.1 ± 1.4 mg/100 ml after 24 hr of fasting (P < 0.05) and did not change significantly after the 1st day of fasting. The whole blood fructose concentration in the fetal artery was high in the fed state (71.7 ± 11.5 mg/100 ml, mean 2 days before fasting) and fell quickly during starvation (34.2 ± 3.4 mg/100 ml after 48 hr). The fructose concentration did not change further for the duration of the fasting period. The fetal arterial insulin concentration was lower than the maternal (19.4 ± 1.0 uU/ml in the fed state and did not fall dramatically after fasting as the mother did. After 24 hr of fasting, the fetal insulin was 15.0 ± 1.5 uU/ml (P < 0.005) and remained low throughout the fast. The umbilical venous-arterial differences of insulin were statistically different from 0 in both fed (mean – 1.4 ± 0.3 uU/ml; P < 0.005) and fasted state (mean – 1.4 ± 0.5 uU/ml; P < 0.02), with the fetal artery greater than the umbilical vein in 25 of 28 measurements. The fetal arterial concentration of glucagon was lower than in the ewe (32 ± 7 pg/ml) and also did not change significantly during starvation. There was a good correlation of the plasma glucose and insulin concentrations for both the fetus and the ewe. Analysis of pooled fetal and maternal regression lines for insulin-glucose relationships reveals no difference in the slope (maternal 0.48, fetal 0.48), but a statistically significant difference in the y intercept (maternal – 7.70, fetal 8.65, P < 0.005), with the fetal curve shifted to the left. The excellent correlation between plasma glucose and insulin concentration throughout the fed and fasted periods suggests that the decrease in fetal plasma glucose and the decreased utilization of exogenous glucose by the fetus is mediated by fetal insulin level. Although the response of insulin to the change in glucose in the fetus is the same as in the mother, the threshold is set at a lower glucose concentration in the fetus. The data in this study would suggest that glucagon is not an important regulator of fetal metabolism during maternal starvation because there was no significant change in the glucagon concentration in the fetus throughout the study. Speculation: Fetal growth and metabolism appear to be influenced by both substrate availability from the mother and fetal hormonal mechanisms. The role of alanine and the possibility of altering fetal growth by manipulating substrate availability need to be investigated to further understand the fetal metabolic response to maternal nutritional deprivation.