GLUCOCORTICOIDS REGULATE L-FUCOSE GLYCOCONJUGATES IN RAT PANCREATIC ZYMOGEN GRANULES

Lectin-binding studies were performed on rat pancreatic zymogen granul es to investigate the influence of glucocorticoid levels on saccharide membrane composition. The following animal groups were used: (1) cont rol rats; (2) rats treated with hydrocortisone (1, 10 and 25 mg/kg/day ) for 1, 3 and 8 days (3) postadrenalectomized rats at days +1, +3 and +8; and (4) adrenalectomized rats receiving hydrocortisone therapy (1 0 mg/kg/day) for 8 days. By flow cytometry, fluoresceinated (FITC) lec tins were used to measure the amount of Concanavalin A (Con A) (specif ic for D-mannose), wheat germ agglutinin (WGA) (specific for N-acetyl- D-glucosamine) and sialic acids and Tetragonolobus purpureus (TP) (spe cific for L-fucose) bound to individual zymogen granules from two subp opulations, Z1 and Z2, identified on the basis of their forward and si de scatter properties. The molar ratio of the different FITC-lectins r evealed significant differences in the glycoconjugate composition of Z 1 and Z2 granules, the Z1 granules showing higher ratios of N-acetyl-D -glucosalmine:L-fucose and N-acetyl-D-glucosamine:D-mannose, both in c ontrol, adrenalectomized and hydrocortisone-treated rats. II was also observed that N-acetyl-D-glucosamine and/or sialic acids were more abu ndant than L-fucose and D-mannose in the zymogen granule membrane. Z1 and 22 granules had different glycosylation patterns. Neither adrenale ctomy nor hydrocortisone treatments varied the Con A binding to zymoge n granules. An increase in WGA binding was only induced by administrat ion of very high doses of hydrocortisone (25 mg/kg/day) for 8 days, an effect not directly related to glucocorticoids. In contrast, a correl ation between the FITC-TP labelling and glucocorticoid levels can be e stablished, so that, in a lime-dose dependent way, an increase was obs erved in zymogen granules of rats treated with hydrocortisone while a decreased TP binding was found in adrenalectomized rats-an effect whic h was reversed with hydrocortisone therapy. Therefore, glucocorticoids exert a direct influence on the saccharide composition of rat pancrea tic zymogen granules, regulating the amount of L-fucose glycoconjugate s, with Z2 granules more sensitive than Z1 ones. (C) 1997 Elsevier Sci ene Ireland Ltd.