168 



HYPOPHYSIS AND GOXADOTROPHIC HORMONES 



tion, especially in additional species, will 

 reveal its inadequacies. 



V. Secretory Granules 



A. THE NATURE OF SECRETORY GRANULES 



Many of the cells of the pars anterior 

 contain characteristic secretion granules 

 stainable by a variety of procedures which 

 indicate that the granules are composed 

 mainly of characteristic proteins. The se- 

 cretion of the different hormones is inti- 

 mately related to the formation and dis- 

 charge of secretory granules in different 

 cells, and the nature of the hormone secreted 

 by any cell is intimately related to the chem- 

 ical nature of the secretory granules in that 

 cell. The special cytology of the hypophysis, 

 which deals with the differences between 

 cells with different functions, is practically 

 confined to the study of the secretory gran- 

 ules, these being the only truly specific char- 

 acters that can be made visible by current 

 techniques. 



Granules similar to those in the cells of 

 the pars anterior are seen in other tissues 

 where the cells secrete proteins which act as 

 hormones or enzymes. Examples are the 

 granules of the hormone-secreting a- and 

 ^-cells of the pancreatic islets, and the 

 zymogen granules of the enzyme-secreting 

 acinar cells of the pancreatic parenchyma. 

 The nature of zymogen granules of the pan- 

 creas and the relationship of the granule to 

 the secretory process have been clarified by 

 the epoch-making researches of Palade 

 (1956 », and of Siekevitz and Palade (1958a, 

 b). 



As seen in electron micrographs, the zy- 

 mogen granules in the guinea pig pancreas 

 are spherical bodies about 600 m/x in di- 

 ameter. At certain stages in their formation 

 a smooth membrane becomes visible at the 

 periphery. It may be assumed that zymogen 

 granules are bound by a smooth-surfaced 

 membrane throughout their intracellular 

 existence, and that, when in the fully 

 formed granule an enclosing membrane is 

 not visible in electron micrographs, it is be- 

 cause it is closely applied to the homo- 

 geneous content of equally high density. 



Secretion of zymogen into the ducts after 

 feeding the previously fasted guinea pig re- 

 sults in the disappearance of membrane-en- 



closed granules from the apical pole of the 

 cell and the appearance of the dense content 

 of the granule without enclosing membranes 

 in the lumen of the duct. Apparently the 

 enclosing membranes are left behind at the 

 cell border and therefore presumably coa- 

 lesce with the cell membrane during the 

 passage of the granule through this struc- 

 ture. 



Restoration of the cell content of enzymes 

 and enzyme precursors occurs rapidly af- 

 ter secretory discharge. These products are 

 formed in the basal part of the cell in which 

 the synthesizing system is located. This sys- 

 tem is revealed in electron micrographs as a 

 closely packed arrangement of rough-sur- 

 faced membranes forming part of the endo- 

 plasmic reticulum. In light microscopy it 

 is revealed by the cytoplasmic basophilia 

 due to the ribonucleic acid component of 

 the system. It is especially to be noted that 

 the formation of the secretory product is 

 not accompanied by any formation of mem- 

 brane-enclosed zymogen granules, but dense 

 material in a more or less diffuse form ap- 

 pears in the cavities of the endoplasmic re- 

 ticulum. The filling of relatively large vesi- 

 cles in the Golgi zone with dense material 

 and the accumulation of membrane-en- 

 closed zymogen granules in the apical re- 

 gion of the cell occur relatively late in the 

 secretory cycle and seem to result from in- 

 tracellular transport and enclosure in mem- 

 branes of products synthesized earlier in 

 the basal region. 



One implication of these observations is 

 that a hormone could be formed and re- 

 leased by an endocrine cell without being 

 stored in the form of granules. This is pos- 

 sible inasmuch as the granule does not play 

 any part in the formation of the secretion. 



Electron microscopy of the rat hypophy- 

 sis indicates that the granules are similar in 

 structure to zymogen granules of the pan- 

 creas. The enclosing membrane is easily 

 visible in the basopiiil granules of the pars 

 anterior and in the neurosecretory granules 

 of tlic pars nervosa as an electron-dense 

 nienibrane enclosing a less dense content. 

 The acidophil granules of pars anterior 

 cells, like the zymogen granules of the pan- 

 creas, seem to contain solid protein of a 

 density that does not permit the demon- 

 stration of an enclosing membrane except in 



