Modulation of growth hormone secretion by thermogenically derived free fatty acids in the perinatal lamb

To evaluate the hypothesis that the rapid fall in circulating GH concentrations at birth is secondary to the initiation of nonshivering thermogenesis and the consequent rise in FFA levels, a series of experiments was performed in late-gestation fetal sheep. By sequentially cooling the fetus by means of a coil placed around the fetal thorax, ventilating with oxygen via an exteriorized tracheostomy tube, and separating the fetus from the placenta by occluding the umbilical cord, nonshivering thermogenesis could be induced in utero. In the first protocol (n = 6) cooling alone had no effect on fetal plasma FFA levels, oxygenation elevated FFAs slightly from 64 +/- 7 mu Eq/liter to 183 +/- 29 mu Eq/liter, and cord occlusion caused a further marked rise (P less than 0.005) to 635 +/- 69 mu Eq/liter. Neither cooling nor ventilation affected fetal plasma GH concentrations which fell (P less than 0.001) from 160 +/- 17 ng/ml to 65 +/- 13 ng/ml upon cord occlusion. When the cord occluder was removed FFA levels fell (P less than 0.001) and GH concentrations rose (P less than 0.001) once more, and when the cord was again occluded FFA levels rose (P less than 0.001) and GH concentrations fell (P less than 0.001). In a second protocol nine fetuses were cooled, ventilated, and the umbilical cord occluded. Once more, plasma FFA levels rose (P less than 0.001) and GH concentrations fell (P less than 0.001); when thermogenesis was inhibited by the infusion of the adenosine agonist N6-(L-2-phenyl isopropyl)-adenosine, FFA levels fell from 725 +/- 88 mu Eq/liter to 265 +/- 56 mu Eq/liter and GH concentrations rose from 54 +/- 13 ng/ml to 323 +/- 73 ng/ml. In two further protocols the possibility that PIA was acting directly on GH secretion was excluded in six fetuses with low plasma FFA levels and in three fetuses with elevated plasma FFA levels secondary to a fatty acid emulsion infusion. These studies provide direct evidence that the pattern of change in plasma GH concentrations at birth in the sheep is determined in part by the rise in plasma FFAs of thermogenic origin.