Hypothalamic enzymatic activities capable of degrading LHRH may play a physiological role in the neuroendocrine control of LHRH. There is increasing evidence, however, that these enzymes are not peptide specific. The present study in the ewe analyzed the possibility that the specificity of LHRHdegrading activity (LHRH-DA) could be conferred by the relative location of LHRH-DA with respect to that of the LHRH peptide itself. LHRH content was correlated with LHRH-DA in discrete hypothalamic samples containing LHRH-positive cell bodies and axons and in immediately adjacent areas apparently devoid of LHRH immunoreactivity. LHRH content was assessed by RIA, and LHRH-DA was determined by HPLC of the LHRH decapeptide and its degradation fragments. The sampling of discrete hypothalamic areas was designed after immunocytochemical localization of LHRH. LHRH-containing cell bodies were observed in the medial preoptic area, projecting LHRH-positive fibers to the infundibular region. At all hypothalamic levels, there was a tight correlation (r > 0.95; P < 0.01) among the regional distribution of LHRH-DA, LHRH content, and the presence of LHRH-like immunoreactivity. LHRH-DA, in addition, was present in areas of low (e.g. lateral hypothalamus) or undetectable (e.g. cerebral cortex) LHRH content that were devoid of LHRH-like immunoreactivity. The appearance of LHRH degradation fragments suggests that the initial cleavage of LHRH by LHRH-DA occurs at the Tyr6-Gly6 bond at all hypothalamic levels studied. These findings indicate that part of the total hypothalamic LHRH-DA may be located within the LHRH hypophysiotropic pathway. This suggests an anatomical locus for a possible physiological interaction between LHRH and LHRH-DA.
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