Further characterization of the extra-arcuate alpha-melanocyte stimulating hormone-like material in hypothalamus: Biochemical and anatomical studies

Abstract

Previous studies had shown the existence of an extra-arcuate cell group in lateral hypothalamus which contains alpha-melanocyte stimulating hormone (a-MSH)-like immunoreactivity, but no other pro-opiomelanocortin (POMC) immunoreactivity. The question we have attempted to address in this series of studies is whether the material is indeed a-MSH or a cross-reacting material. Chromatographic studies failed to detect any material which is different from a-MSH or des-acetyl-a-MSH, suggesting that either the material is authentic a-MSH/des-acetyl-a-MSH, or that it is not detected by our RIAs. A series of manipulations including dissections of arcuate vs. extra-arcuate hypothalamic areas, treatment with colchicine, lesions with monosodium glutamate and knife cuts were aimed at isolating the extra-arcuate region and showing that it contains an excess of a-MSH over beta-endorphin (B-END), presumably deriving from the extra-arcuate group. However, all studies showed parallel changes in a-MSH and B-END, suggesting that we were not detecting a non-POMC derived a-MSH in these studies. This led to the tentative conclusion that the material was not a-MSH and was not being detected by our RIA's. This hypothesis was tested by further characterizing the material immunohistochemically. These studies led to the conclusion that the extra-arcuate material had a carboxy-terminal homology with a-MSH but differed from it in the midregion, since antisera directed at the 4-10 region of a-MSH failed to stain this non-POMC cell group. Finally, the anatomy of this extra-arcuate group is described, particularly the projections to the striatum, hippocampus, neocortex and olfactory bulb.