HYP0PHY8EAL MORPHOLOGY 



169 



thoye graniilcs tliat are only ixartially filled 

 (Farquhar and Wellings, 1957). 



There is no necessity for secretory gran- 

 ules to contain a single substance. The zy- 

 mogen granules of the pancreas contain a 

 mixture of enzymes and enzyme precursors. 

 It is certain that some granules in the hy- 

 pophysis contain a mixture of materials, 

 some hormonal and others not hormonal. 

 The staining reactions of specific granules 

 may therefore be due to a nonhormonal con- 

 stituent. This seems to be true of acidophil 

 granules in the pituitary, inasmuch as the 

 characteristic staining is due to a protein 

 which is highly insoluble over a wide range 

 of pH, whereas the hormones characteristic 

 of these cells, growth and lactogenic hor- 

 mone, are more soluble and can be extracted 

 by procedures which do not dissolve the 

 characteristic protein. Similar considera- 

 tions apply to the neurosecretion in the 

 nerve fibers of the neural lobe, because the 

 characteristic hormones are octapeptides, 

 whereas the characteristic staining is due to 

 a protein with high cystine content presum- 

 ably identical with the van Dyke protein 

 I van Dyke, Chow, Creep and Rothen, 1942) . 

 The granules of basophil cells contain glyco- 

 protein, and the characteristic staining reac- 

 tions seem to be due to the glycoproteins 

 because they are similar to the staining reac- 

 tion seen in other sites containing glycopro- 

 tein. In the basophil cells, however, it is not 

 known whether the glycoproteins responsible 

 for the staining reactions are identical with 

 the hormones or whether they exist in the 

 vesicular glands in association with hormo- 

 nally active molecules themselves not stain- 

 able or not made visible by staining reac- 

 tions because of their low concentration. 

 Parallelism between intensity of staining 

 and hormone content, which has been used 

 to support the claim that it is the hormone 

 product itself of these cells which is stained, 

 does not in fact contribute to the solution 

 of this problem. Staining reactions demon- 

 strate the numbers of granules present, and 

 parallelism between staining and hormone 

 content indicates that the hormone is like- 

 wise contained within the granule. Chemi- 

 cal investigation of the nature of the iso- 

 lated hormones and of the protein materials 

 responsible for the staining reactions is the 

 only source of evidence which might show 



that the staining reactions are due to a 

 product distinct from the hormonally ac- 

 tive product. This may be regarded as 

 established for acidophil cell granules, neu- 

 rosecretory granules, and for the glycopro- 

 tein granules of the pars intermedia cells, 

 but has not been established for glycopro- 

 tein-containing cells of the basophil cells 

 of the pars anterior. In this site, therefore, 

 it is still possible that the staining reactions 

 arc due to the hormonally active product 

 itself and not to any associated but hor- 

 monally inactive protein. 



B. THE STAINING REACTIONS OF SECRETORY 

 GRANULES BY MODERN METHODS 



The recognition of a diversity of cell 

 types in the pars distalis as reported by 

 Schonemann (1892) dei)ends on the pres- 

 ence of distinctive proteins in different cells. 

 Although at one time theories which made 

 the different cell types stages of a secre- 

 tory cycle had a certain popularity, we 

 now know that the different cell types made 

 visible by staining methods have different 

 secretory functions. This was first demon- 

 strated by the observations of Smith and 

 Smith (1923a, b). This momentous experi- 

 ment showed a diversity of endocrine func- 

 tion in the anterior lobe and a correlation 

 between function and type of cell. It also 

 destroyed the hypothesis that different cell 

 types could be merely different phases of 

 a secretory cycle. All these results followed 

 from the demonstration that in the bovine 

 hypophysis there is constantly present a 

 zone situated anteromedially which is poor 

 in acidophil cells and, therefore, is mainly 

 comprised of basophil cells and chromo- 

 phobes. The tissue from this zone im- 

 planted into tadpoles had a predominantly 

 thyroid-stimulating and consequent meta- 

 morphosis-inducing effect, whereas tissue 

 rich in acidophils promoted body growth 

 and was poor in thyroid-stimulating action. 

 It is clear, then, that staining reactions in 

 pituitary cells may be related to the nature 

 of the hormone produced, and we may, 

 therefore, consider in what manner the 

 staining reactions are linked to the specific 

 function. Although it is reasonable to as- 

 sume that differences in the product of dif- 

 ferent cells arise from variations in their 

 enzvme content, the slight differences in 



