PRODUCTION AND SECRETION OF N-TERMINAL SECRETOGRANIN-II DERIVED PEPTIDES IN GH3B6 PROLACTIN CELLS

Chromo/secreto-granins are proteins specific of neuroendocrine cells. Chromogranin B (CgB) and secretogranin II (SgII) are both present in n ormal and in tumoral (GH3B6) prolactin cells, in which they are coloca lized in the same secretory granules. These proteins contain multiple dibasic cleavage sites and are considered as potential precursors of a ctive peptides, though their exact function remains unknown. SgII is s ulfated on tyrosine-126. We took advantage of this feature to study it s post-translational processing in anterior pituitary cells in primary culture and in GH3B6 cells. Pulse-chase experiments with [S-35]sulfat e demonstrated the precursor-product relationship between SgII and fou r N-terminal-derived peptides. Kinetic experiments showed the sequenti al cleavage of SgII from the C-terminus to the N-terminus. Mature SgII and the derived peptides were secreted by both cell models, and their release was stimulated by TRH (30 nM), a secretagogue of prolactin. T hese data show that SgII is proteolytically processed into different s ecreted peptides in prolactin cells and demonstrate that GH3B6 cells p rovide a good cell model for studying the maturation of SgII in anteri or pituitary.