HYPOPHYSEAL MORPHOLOGY 



195 



the rat. By immersing bat hypophyses in 

 10 per cent trichloracetic acid for 12 hours 

 before fixation Herlant found that the gran- 

 ules of FSH cells were soluble, those of the 

 LH cells insoluble in this medium. 



IX. Corticotrophin : the Problem of 

 Its Origin 



A. BASOPHIL CELLS AND CORTICOTROPHIN 



Many attempts have been made to re- 

 late corticotrophin secretion to one or other 

 of the specific cell types demonstrable by 

 staining reactions, but the results have 

 generally been inconclusive. The distribu- 

 tion within the anterior lobe of species 

 which show distinct zoning is instructive. 

 Smelser (1944) showed that corticotrophin 

 was more concentrated in the basophil zone 

 of the bovine pars anterior than in the 

 acidophil zone. In the pig pars anterior, in 

 which the zones are much more distinct, 

 I have found that corticotrophin is present 

 in portions of the anteromedial basophil 

 zone that are apparently free from acidophil 

 cells, the concentration there being 2 to 

 4 times that in the posterolateral acido})hil 

 zone. The assays were made by the ascorbic 

 acid depletion method. Giroud and Mar- 

 tinet (1948) found that the adrenal weight- 

 increasing action is predominantly situated 

 in the basophil zone. Rochefort and Saffran 

 (1957) found 4 to 13 times as much corti- 

 cotrophin in the anteromedial basophil 

 zone of pig and beef hypophyses as in the 

 posterolateral parts of the acidophil zone. 

 Certainly in both cow and pig the corti- 

 cotrophin is not in acidophil cells. In the 

 cow it may be in either basophils or chromo- 

 phobes, but in the pig it seems certain that 

 it must be in some type of basophil cell, 

 because there are few chromophobes in the 

 pig pars anterior and a large part of the 

 basophil zone is free of them ancl consists of 

 basophil cells only. 



Halmi and Bogdanove (1951) and Hess, 

 Slade, Amnions and Hendrix (1955) found 

 that the loss of acidophil granules in the 

 thyroxine-deficient rat was not accom- 

 panied by any change in the content of 

 corticotrophin in the hypophysis, nor was 

 there any change in corticotrophin output. 

 This indicates that the hormone is not in the 



acidophil granules in this species and is 

 probably not formed by acidophil cells. 



One indication of the possible nature of 

 the granules to be expected in corticotro- 

 phin-secreting cells may be made from the 

 the chemical nature of their hormonal prod- 

 uct. This polypeptide has some relationship 

 to intermedin, and the amino-acid sequence 

 — methionine, glutamic acid, histidine, 

 phenylalanine, arginine, tryptophan, gly- 

 cine — is common to both (Landgrebe and 

 Mitchell, 1958) . The presence of this struc- 

 ture in corticotrophin may account for its 

 having some intrinsic melanin-dispersing 

 properties. The intermedin-secreting cells of 

 the pars intermedia may in some species 

 have enough specific granulation to dis- 

 tinguish them from chromophobes, but when 

 granules are present they are basophil gran- 

 ules containing glycoprotein and are stain- 

 :ible with aldehyde-fuchsin. We might 

 expect, therefore, that if corticotrophin- 

 secreting cells contain granules they will 

 be basophil granules, although it is not 

 necessary that they should contain such 

 granules. 



The origin of corticotrophin from baso- 

 phil cells has gained a certain degree of 

 acceptance based on the association of baso- 

 phil cell adenomas with the Gushing syn- 

 drome in man. The evidence now is that 

 these basophil cell changes are the result 

 of the action of excess adrenal steroids and 

 are not the cause of the syndrome even in 

 those cases which seem to be due to ex- 

 cessive secretion of corticotrophin. This 

 aspect of the subject is dealt with more fully 

 in the later section on Gushing's syndrome. 



The attempt by Marshall (1951) to dem- 

 onstrate the presence of corticotrophin in 

 basophil cells by the use of labeled antibody 

 must be discussed, because it has been re- 

 garded by some as a conclusive demonstra- 

 tion of the relation of this hormone to baso- 

 phil cells. The antibody labeled with a 

 fluorescent grouping demonstrated the pres- 

 ence in basophil cells of an antigen which 

 had been contained in the crude corti- 

 cotrophin preparation used. There is, how- 

 ever, nothing to associate the antigen so 

 demonstrated with the corticotrophin. Such 

 protein-containing preparations of corti- 

 cotrophin seem to contain many more 

 molecules of protein than of corticotrophin, 



