Dopaminergic Agents Differentially Regulate Both Processing and Content of α-N-Acetylated Endorphin and α-MSH in the Ovine Pituitary Intermediate Lobe

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Abstract
Hypothalamo-pituitary disconnection (HPD) in the sheep results in a two-fold increase in pituitary intermediate lobe (IL) immunoreactive (ir)-α-N-acetylated endorphin (NacEP) and ir-α-melanocyte-stimulating hormone (αMSH) content. The rise in IL NacEP content is accompanied by a markedly altered pattern of processing, in that NacEP1–27 becomes the dominant molecular species with a complementary fall in Nacα-EP and Nacγ-EP. To determine if these effects reflect the loss of descending dopaminergic neuronal input to the IL, we have chronically treated two groups (n = 4 per group) of normal sheep with the dopamine antagonist haloperidol or the dopamine agonist bromocriptine; a group of HPD sheep were also treated with bromocriptine. Acid extracts of IL were diluted and ir-α-MSH and ir-NacEP content determined by radioimmunoassay; aliquots were submitted to reversed-phase HPLC and collected fractions similarly assayed. Bromocriptine lowered ir-NacEP and ir-α-MSH by about 30%; on HPLC the ir-NacEP profiles, and perhaps to a lesser extent those for ir-α-MSH were qualitatively similar to untreated controls. In contrast, haloperidol increased by about 45% both ir-NacEP and ir-α-MSH levels and produced a marked change in the ir-NacEP molecular profile, with NacEPι_27 becoming the predominant molecular form and other species representing only minor components in the chromatogram. In the treated HPD group, bromocriptine partially restored the processing profiles previously observed in HPD animals to those found in untreated intact animals. These data suggest that not only is synthesis of pro-opiomelanocortin peptides in the sheep IL under tonic inhibitory dopaminergic control but that regulation of NacEP processing in the IL may also be mediated via dopaminergic neurons, probably arising from the medial basal hypothalamus.

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