The role of the pituitary-thyroid axis in the developmental regulation of enkephalin-containing peptides in the superior cervical ganglia and adrenal of the fetal sheep

We have postulated that sympathetic neurones may be one source of circulating enkephalins in the fetus. Therefore, we have investigated the effects of increasing gestational age on the content of the enkephalin-containing peptides in the superior cervical ganglia (SCG) of the fetal sheep during late gestation. We have also investigated the role of the pituitary-thyroid axis in the coordinate regulation of enkephalin-containing peptides within the fetal sympathoadrenal system. We found an increase (P0.05) in the content of Free Met-O-Enkephalin between 85 and 105 days (d) (0.46 +/- 0.12 nmoles/SCG) and 116 and 125 d (0.93 +/- 0.12 nmoles/SCG), and the SCG content of Free Met-O-Enkephalin remained elevated throughout the remainder of gestation. The fetal SCG content of Total Met-O-Enkephalin also increased significantly between 85 and 105 d (2.8 +/- 0.5 nmoles/SCG) and 116 and 125 d (7.1 +/- 1.2 nmoles/SCG). There was, therefore, no change in the ratio of Total:Free Met-O-Enkephalin content of the SCG between 85 and 145 d. There were no significant effects of fetal hypophysectomy with or without thyroxine (T4) replacement on the content of Free Met-O-Enkephalin (intact, 1.11 +/- 0.18 nmoles; hypophysectomy (HX) + Sal, 1.41 +/- 0.25 nmoles; HX + T4, 1.08 +/- 0.27 nmoles) or Total Met-O-Enkephalin (intact, 3.03 +/- 0.90 nmoles; HX + Sal, 4.03 +/- 0.22 nmoles; HX + T4, 3.53 +/- 0.88 nmoles) in the fetal SCG. The adrenal contents of Free and Total Met-O-Enkephalin were, however, significantly reduced after fetal hypophysectomy and these effects were not altered by replacement with T4 after fetal hypophysectomy. In summary, we have demonstrated for the first time that enkephalin-containing peptides are present in the SCG of the fetal sheep and that the SCG enkephalin content increases between 85 and 125 days gestation. We have found no evidence that there is a change in the post-translational processing of the enkephalin precursor to Free Met-Enkephalin within the SCG during the second half of gestation. In contrast to the fetal SCG, maintenance of adrenal enkephalin content in late gestation is dependent on the presence of an intact fetal pituitary, but is independent of the circulating concentrations of thyroxine.