Effects of Hypoxia on β-Endorphin and β-Lipotropin Release in Fetal, Newborn, and Maternal Sheep*

Abstract

Plasma β-endorphin immunoactivity was measured in chronically catheterized fetal, newborn, and maternal sheep before, during, and after periods of controlled hypoxia induced by having the pregnant ewe or newborn lamb breathe a gas mixture of 10% oxygen in nitrogen for 30 min. In 13 fetuses, mean (±SEM) β-endorphin immunoactivity increased from 125 ± 24.9 to 503 ± 73 pg/ml at 30 min of hypoxia (P < 0.001); simultaneous mean maternal β-endorphin immunoactivity did not rise during hypoxia. In contrast to the fetal lamb, no change in β-endorphin immunoactivity was noted in 3 newborn lambs, 1–11 days old, in response to breathing 10% oxygen. Sephadex G-50 chromatography of plasma extracts from 7 fetuses (6 before and during hypoxia) showed that the increase in total β-endorphin immunoactivity in response to hypoxia consisted of increases in both β-endorphin and β-lipotropin (β-LPH) concentrations. The mean β-endorphin to β-LPH molar ratio of 0.80 in the fetus in the baseline state was significantly higher than the mean molar ratio of 0.33 measured during hypoxia. Although breathing 10% oxygen failed to stimulate β-endorphin release in the adult and newborn sheep, the calculated hemoglobin oxygen saturation in these animals was significantly higher than that in the fetuses when this mixture was breathed. A stronger hypoxemic stimulus, induced by breathing 5% oxygen and designed to produce a hemoglobin oxygen saturation similar to that in the fetus in response to 10% oxygen, caused a rise in β-endorphin in all of six adult and three newborn sheep. We conclude that: 1) high levels of β-endorphin and β-LPH circulate in the fetal lamb and increase markedly in response to hypoxia, with relatively more β-LPH than β-endorphin being secreted during hypoxia than in the baseline state; 2) the failure of maternal plasma β-endorphin immunoactivity to increase in response to breathing 10% oxygen indicates that the increased β-endorphin and β-LPH in the fetus caused by this stimulus is not of maternal origin; and 3) hypoxia, if severe enough, stimulates β-endorphin secretion in the adult ewe and newborn lamb as well as in the fetus. (Endocrinology108: 1710, 1981)