Lower serum activity of prolyl endopeptidase in anorexia and bulimia nervosa

The aim of this study was to examine whether anorexia and bulimia nervosa a re accompanied by lower serum activity of prolyl endopeptidase (PEP;EC 3.4. 21.26; post-proline cleaving enzyme), a cytosolic endopeptidase which cleav es peptide bonds on the carboxyl side of proline in proteins of relatively small molecular mass. Substrates of PEP are, amongst others, neuroactive pe ptides, such as arginine vasopressin, luteinizing hormone-releasing hormone , thyrotropin releasing hormone,alpha -melanocyte secreting hormone, substa nce P, oxytocin, bradykinin, neurotensin and angiotensin (Ag) I and II. Ser um PEP activity was measured in the serum of 18 normal women, 21 anorexia n ervosa and 21 bulimia nervosa women by means of a fluoremetric method. The Bulimic Investigatory Test, Edinburgh (BITE), the Eating Disorder Inventory (EDI) and the Hamilton Depression Rating Scale (HDRS) were scored. Serum P EP activity was significantly lower in patients with bulimia nervosa and an orexia nervosa, irrespective of the restricted or binging subtype, than in normal controls. There were significant and inverse correlations between se rum PEP activity and the HDRS and BITE. In anorectic patients, but not in n ormal or bulimic patients, there was a significant correlation between seru m PEP and body mass index. In bulimic patients, but not in normal or anorec tic patients, then was a significant correlation between serum PEP and dura tion of illness. It is concluded that lowered serum PEP activity takes part in the pathophysiology of anorexia and bulimia nervosa. It is hypothesized that a combined dysregulation of PEP and neuroactive peptides, which are s ubstrates of PEP, could be an integral component of eating disorders. (C) 2 000 Elsevier Science Ltd. All rights reserved.