Role of prostaglandin E2 and prostacyclin in nonshivering thermogenesis during simulated birth in utero.

Prostaglandin E2 (PGE2) inhibits and prostacyclin (PGI2), stimulates lipolysis in vitro. Their role in initiating nonshivering thermogenesis at birth was investigated in 16 fetal sheep at 129-143 days gestation. In 10 fetuses indomethacin, a prostaglandin synthesis inhibitor, was infused; in 6 fetuses saline was administered as a control. 16 h later birth was simulated in utero. The plasma levels of PGE2 and PGI2 were unaffected by cooling. In the control fetuses, ventilation with oxygen caused PGE2 to fall, PGI2 to rise, and initiated moderate thermogenesis, signaled by a twofold increase in plasma free fatty acids (FFA). After umbilical cord occlusion, PGE2 decreased further (PGI2 was unchanged) and thermogenesis accelerated. In indomethacin-treated fetuses, in which the prostanoids had decreased and remained at approximately 20% normal, cooling initiated moderate nonshivering thermogenesis, and ventilation and cord occlusion caused no further changes. Changes in plasma adenosine were similar in control and indomethacin-treated groups. We conclude that declining PGE2 and rising PGI2 contribute to the initiation of thermogenesis at birth, but that other agents possibly of placental origin may play a contributory role.