Distribution of proSAAS-derived peptides in rat neuroendocrine tissues

Using a technique to identify substrates of the peptide processing enzyme c arboxypeptidase E (CPE), several novel peptides were detected in the brain and pituitary of Cpe(fat)/Cpe(fat) mice and found to be derived from a sing le precursor, termed proSAAS. In order to gain further information regardin g the potential physiological roles of these peptides, we have examined the distribution of two proSAAS-derived peptides, ARPVKEPRSLSAASAPLAETSTPLRL ( SAAS) and LENSSPQAPARRLLPP (LEN), in rat neuroendocrine tissues using immun ohistochemistry. Both peptides are detected throughout the brain, with the highest concentrations of SAAS peptide in the hypothalamus. In the hippocam pus, both peptides are co-localized with prohormone convertase I in the den tate gyrus and CA1-3 region. In cerebellum, SAAS peptide is co-localized wi th prohormone convertase I in Purkinje and granular cells, whereas LEN is m uch more abundant in the Purkinje cells relative to the granular cells. Sim ilarly, SAAS and prohormone convertase I are co-localized in the dorsal hor n of the spinal cord, while LEN is mainly restricted to fibers of the white matter. In the pituitary, SAAS, LEIN, and prohormone convertase I are dete cted in all three lobes. In the pancreas, SAAS, LEN, and prohormone convert ase I are only detected in the islets, although the peptides are enriched i n the peripheral cells (alpha and/or delta) while prohormone convertase I i s only expressed in the inner cells (beta). Both SAAS and LEN are present i n the adrenal medulla along with prohormone convertase 1. Taken together, these data are consistent with the proposed role for proSAA S as an endogenous inhibitor of prohormone convertase I in many, but not al l cell types. However, the broader localization of the peptides allows for the possibility that they perform additional functions. (C) 2001 IBRO. Publ ished by Elsevier Science Ltd. All rights reserved.