Proopiolipomelanocortin Peptides in Normal Pituitary, Pituitary Tumor, and Plasma of Normal and Cushing's Horses*

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Abstract
Using RIAs for six regions within proopiolipomelanocortin (proOLMC), gel filtration, and electrophoresis, we studied pituitary peptides in a normal horse and one with Cushing's disease caused by a pars intermedia adenoma. Almost all immunoreactive (IR) ACTH (78%) was 4,500 mol wt (4.5 K) ACTH in normal pars distalis, but it was almost 100% corticotropin-like intermediate lobe peptide (CLIP) in normal pars intermedia. αMSH and βMSH were found mainly in pars intermedia; equal concentrations of the βMSH precursors, β-lipotropin (βSLPH) and γLPH, were found in pars distalis. Most IR-β-endorphin (IR-βEND) was found as βEND in pars intermedia, but roughly equal concentrations of βEND and its precursor, βLPH, were found in pars distalis. A 33 K molecule containing IR-ACTH, IR-γ3MSH, and IRβEND, presumed to be proOLMC, and a variety of 15-27 K presumed biosynthetic intermediates were found in both normal pars distalis and pars intermedia. The pars intermedia adenoma causing Cushing's syndrome contained high IR-peptide concentrations. Several differences in precursors were noted, including the presence of three larger presumed precursors (38.5 K, 47 K, and 63 K) that had both ACTH and βEND immunoreactivities and both deletions and additions of 15–27 K intermediates. The Cushing's horse's plasma peptides reflected tumor concentrations; 4.5 K ACTH was modestly elevated, but the concentrations of CLIP, αMSH, βMSH, γLPH, and βEND were dramatically increased. About 20% of plasma IR-ACTH and 5% of IR-βMSH and IR-βEND were found as high molecular weight forms. Normal processing of horse proOLMC appears to be similar to that in other species, but may be altered in pars intermedia tumors of horses with Cushing's disease, the plasma of which contains disproportionately increased concentrations of pars intermedia proOLMC peptides.

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