Dopaminergic regulation of alpha-melanocyte-stimulating hormone and N-acetyl-beta-endorphin secretion in the fetal lamb.

Abstract

alpha MSH is present in high concentrations in the intermediate lobe of the fetal pituitary and has been implicated as a regulator of fetal adrenal steroidogenesis and fetal growth. However, there are few data regarding alpha MSH levels in fetal plasma or the control of fetal alpha MSH secretion. We measured alpha MSH immunoactivity in the plasma of chronically catheterized fetal lambs (gestational age, 116-138 days), newborn lambs, and adult sheep both in the baseline state and after dopamine receptor blockade with metoclopramide. The effect of metoclopramide on the release of another proopiomelanocortin-derived peptide, N-acetyl-beta-endorphin (N-acetyl-beta EP), which is synthesized together with alpha MSH in the intermediate lobe, was also studied. Baseline fetal plasma alpha MSH was significantly greater than maternal alpha MSH [35.6 +/- 2.2 (+/- SEM) vs. 10.0 +/- 1.0 pg/ml]. In eight studies in five fetal lambs, alpha MSH rose to a peak level of 121 +/- 23 pg/ml 15 min after metoclopramide administration to the fetus. Simultaneous maternal alpha MSH levels did not change, suggesting that the alpha MSH in fetal plasma was of fetal pituitary origin. Gel filtration of pooled fetal plasma extracts revealed that the alpha MSH immunoactivity eluted in the same position as the alpha MSH standard. Metoclopramide caused the secretion of nearly equimolar amounts of alpha MSH and N-acetyl-beta EP into fetal plasma. In four fetal lambs, basal N-acetyl-beta EP levels of 156 +/- 34 pg/ml rose to 305 +/- 65 pg/ml 15 min after metoclopramide treatment. Metoclopramide also stimulated plasma alpha MSH in newborn and adult sheep. In six newborn lambs, alpha MSH rose from 45.2 +/- 13 to 211 +/- 38 pg/ml 15 min after metoclopramide treatment, whereas in four adult sheep, a basal alpha MSH level of 11.1 +/- 2.2 pg/ml rose to 20.1 +/- 2.7 pg/ml 15 min after metoclopramide. In addition, metoclopramide stimulated fetal and neonatal PRL secretion, but had no effect on plasma vasopressin concentrations or acid-base and blood gas values. These studies indicate that immunoreactive alpha MSH and N-acetyl-beta EP are secreted into ovine fetal plasma and that the secretion of these peptides in the fetus appears to be under tonic dopamine inhibition, as is the case in the adult sheep and newborn lamb.