Role of prostaglandin I2 and prostaglandin E2 in the initiation of nonshivering thermogenesis during the simulation of birth in utero.
Because maximal nonshivering thermogenesis can commence only after occlusion of the umbilical cord, circulating stimulators and inhibitors were hypothesized to alter brown fat activity in the perinatal period. The roles of prostaglandin I2 (PGI2) and PGE2 in the initiation of nonshivering thermogenesis at birth were investigated. Indomethacin (45 mg bolus, 3 mg h-1 thereafter) was infused into 10 near-term fetal sheep to decrease prostanoid synthesis; 6 age-matched fetuses were infused with saline as controls. Sixteen hours later, birth was simulated in utero by sequentially cooling the fetus, ventilating its lungs with oxygen and occluding the umbilical cord. In the control fetuses, the plasma concentrations of PGI2 and PGE2 and free fatty acids, an index of nonshivering thermogenesis, were unaffected by cooling. Ventilation caused the concentration of PGI2 to increase 108% (P < 0.001) and that of PGE2 to decrease 26% (P < 0.05), while fatty acid concentrations increased 100% (P < 0.05). After cord occlusion, PGI2 concentrations remained elevated whereas PGE2 concentrations decreased a further 46% (P < 0.01), and fatty acid concentrations increased a further 100% (P < 0.05). In the indomethacin-treated fetuses, PGI2 and PGE2 concentrations decreased to 20% of the preinfusion values (P < 0.001) and did not change during the experiment. Cooling initiated a 300% increase in fatty acid concentrations (P < 0.05) and ventilation and cord occlusion induced no further significant changes. Thus, prostanoid concentrations follow changes in nonshivering thermogenic activity and support a regulatory role for PGI2 and PGE2 in the initiation of thermogenesis. Before birth, high concentrations of PGE2 favour suppression of thermogenesis, and after birth this inhibition is removed and there is stimulation by PGI2.
Ball
K T
KT
Center for Perinatal Biology, School of Medicine, Loma Linda University, CA 92350, USA.
Takeuchi
M
M
Yoneyama
Y
Y
Power
G G
GG
D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology*; D001835:Body Weight; D003080:Cold Temperature; D015232:Dinoprostone / Q000502:physiology*; D011464:Epoprostenol / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005865:Gestational Age; D007213:Indomethacin / Q000494:pharmacology; D007743:Labor, Obstetric / Q000502:physiology*; D008954:Models, Biological; D010100:Oxygen / Q000008:administration & dosage; D011247:Pregnancy; D012756:Sheep
D005230:Fatty Acids, Nonesterified; D011464:Epoprostenol; D015232:Dinoprostone; D010100:Oxygen; D007213:Indomethacin