Relationship between the fall in growth hormone secretion at birth and the onset of nonshivering thermogenesis is independent of beta adrenergic stimulation

Abstract

At the time of birth, many rapid metabolic changes occur including the initiation of nonshivering thermogenesis and a rapid fall in growth hormone concentrations. To evaluate the interaction between these events 5 fetal sheep were studied at 135-144 days' gestation. The fetuses were first cooled 2.22 +/- 0.19 degrees C by circulating cold water through a coil placed around the fetal thorax and then ventilated with oxygen through an exteriorized tracheostomy tube to raise fetal arterial PO2 above 67.5 +/- 14.1 Torr. An hour later the beta adrenergic agonist isoproterenol was infused intravenously for 90 min. The fetuses were then separated from the placenta by occluding the umbilical cord. After 60 min the cooling and then the isoproterenol infusion were stopped and the responses monitored. Basal plasma free fatty acid (FFA 35 +/- 5 microEq L-1) and growth hormone (GH 141 +/- 12 ng mL-1) concentrations were not significantly altered by cooling alone, but oxygenation modestly increased plasma FFA to 237 +/- 55 microEq L-1 (P < 0.01) while GH concentrations fell to 58 +/- 27 ng mL-1 (P < 0.05). Isoproterenol administration did not significantly affect either FFA or GH concentrations. Occlusion of the umbilical cord caused a rapid nearly threefold increase in plasma FFA concentrations to 903 +/- 71 microEq L-1 (P < 0.01) and a fall in the same proportions in GH concentrations to 16 +/- 2 ng mL-1 (P < 0.005). Maximal fetal oxygen consumption was 24.2 +/- 4.4 mL kg-1 min-1. Cessation of cooling induced a significant fall in plasma FFA to 480 +/- 58 microEq L-1 (P < 0.01) and rise in GH concentrations to 46 +/- 5 ng mL-1 (P < 0.01). Following the withdrawal of isoproterenol, the fall in plasma FFA and rise in GH concentrations continued while the fetal oxygen uptake fell to 6.4 +/- 1.7 mliter kg-1 mL-1 (P < 0.01). During the study the variation in plasma GH was inversely correlated with changes in FFA concentrations (R = 0.77, P < 0.001). This study confirms that the major factors initiating nonshivering thermogenesis at birth are: sympathetic stimulation from cutaneous cooling, which was not significantly enhanced by isoproterenol; adequate oxygenation; and removal of placental inhibitor(s). The findings are in agreement with a causal relationship between the initiation of nonshivering thermogenesis and consequent rise in FFA concentrations and the rapid fall in circulating GH concentrations after birth in the lamb, independent of beta adrenergic stimulation.