Theoretical considerations on the formation of secretory granules in the rat pancreas

Rat pancreatic zymogen granule sizes were determined by analysis of electron micrographs of the pancreas from adult and newborn rats. Areas of granule profiles were measured and converted to equivalent volumes. Histograms of the equivalent volumes showed integral multimodal distributions which were evaluated for goodness of fit with two models, unit addition and random fusion. Previous analyses of zymogen granule size distributions have failed to recognize the multimodality we have observed. Distributions of equivalent volumes for the two models were developed using Monte Carlo simulation. In the case of the granules from the newborn rats, the distribution of granule sizes gave a better fit with the random fusion model, whereas the granules from the adult rats had distributions with a better fit to the unit granule addition model. The estimated unit granule sizes for the two different ages were the same. Both unit addition and random fusion models propose that following formation of secretory granules from Golgi-derived material, the granules fuse with one another to create a wide dispersion of granule sizes. The present results extend the evidence for fusional growth of secretory granules, originally developed for the mast cell, to the zymogen granules of pancreas. All normal cells previously studied have yielded secretory granule distributions most consistent with unit addition. The basis for the expression of random fusion in the newborn rather than the more usual unit addition is not known.