Fujictiojial Changes in the 

 Structure of Cell Components 



GEORGE E. PALADE 



Rockeji'ller Institute for Medical Research 



New York, N. Y. 



PHYSIOLOGICAL EVENTS THAT OCCUR at the intracellular level are frequently 

 accompanied by structural changes which deserve careful study because they 

 may suggest, and sometimes indicate, the role played by the afJected structures in 

 the general economy of the cell. As the functional significance of many cell com- 

 ponents is still uncertain or entirely unknown, suggestions or indications of this 

 kind can be particularly valuable. Changes or modulations in cell structure occur 

 at various dimensional levels and some of them are so striking that they were 

 noted early in light microscopy and studied with considerable profit. A conspicu- 

 ous example is represented by the extensive changes in form and distribution un- 

 dergone by the nuclear material during cell division. Our knowledge of the 

 mechanisms operating in hereditary transmission has, in fact, been derived from 

 a detailed analysis of such structural changes, correlated with a careful study of 

 the qualities of the products, in this case the offspring. 



FUNCTIONAL CHANGES IN EXOCRINE CELLS OF PANCREAS 



Heidenhain's Hypothesis. Another example, closer to the subject to be dis- 

 cussed in the following pages, concerns the exocrine cells of the pancreas. As 

 early as 1875, Heidenhain (11) noted that the numerous granules which occupy 

 the apical region of these cells disappear shortly after food intake, to be replaced 

 by apparently new granules a few hours later. By following in time the changes 

 occurring in the apical pole of the exocrine cells, on the one hand, and the varia- 

 tions in the enzymatic activity of the pancreatic juice, on the other hand, Heiden- 

 hain arrived at the conclusion that the granules consist of digestive enzyme pre- 

 cursors. His conclusion rested on the finding that the disappearance of these 

 intracellular bodies, which he called zymogen granules ( 12), coincided in time 

 with the appearance of proteolytic enzymes in the pancreatic juice. According to 

 his interpretation, the zymogen granules represent a temporary intracellular stor- 

 age of digestive enzymes which will be released from the cell at a future food 

 intake. For many years the cyclic variation in the number of zymogen granules 

 discovered by Heidenhain remained the only well established and clearly under- 

 stood event in the physiology of the pancreatic exocrine cell. No real progress was 



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