196 



HYPOPHYSIS AND GONADOTROPHIC HORMONES 



and the antigen could therefore have been 

 one of the glycoprotein hormones known 

 to be antigenic, or some nonhormonal con- 

 stituent. The absence of evidence of anti- 

 genicity in corticotrophin would make the 

 method inapplicable for this hormone unless 

 it could be shown that the hormone w^as 

 associated in the gland with a specific pro- 

 tein. There is no evidence so far that this 

 is the case, because under certain circum- 

 stances the hormone is dialyzable from 

 crude pituitary extracts (Tyslowitz, 1943; 

 Geschwind, Hess, Condliffe, Evans and 

 Simpson, 1950j , and in the extract it seems 

 to be distributed indiscriminately among 

 most of the proteins present (Astwood, 

 Raben and Payne, 1952). 



In the rat three types of basophil cells 

 have been identified, and the question arises 

 whether one of these secretes corticotrophin 

 in addition to its specific glycoprotein hor- 

 mone. The hypothesis that thyrotrophs may 

 secrete corticotrophin has attracted some 

 attention and has been subjected to specific 

 investigation. Halmi and Bogdanove (1951) 

 concluded that corticotrophin was not pro- 

 duced by thyrotrophs in the rat. In the pig 

 hypophysis I have found, as Smelser (1944) 

 found in the bovine hypophysis, that the 

 distribution of the hormones between the 

 basophil and acidophil zones is quite differ- 

 ent for corticotrophin and thyrotrophin, the 

 latter being almost exclusively in the baso- 

 phil zone. This seems to make it certain 

 that the same cell does not produce these 

 two hormones. 



The problem of the origin of corti- 

 cotrophin thus seems to resolve into a choice 

 between two alternatives: either corti- 

 cotrophin is made by gonadotrophs, or it 

 is made by an aditional specific cell type, 

 the "corticotroph." Inasmuch as five spe- 

 cific cell types have been identified in the 

 pars anterior of the rat and the bat, the 

 search for an additional cell type which 

 could be the corticotroph may be referred 

 to as the search for a sixth cell type. In- 

 vestigations aimed at the solution of this 

 problem usually take the form of examin- 

 ing hypophyses in which corticotrophin se- 

 cretion is proceeding at an abnormally rapid 

 rate, and looking for cellular responses 

 either in sections stained by methods which 

 reveal acidophils and basophils or in sec- 



tions stained by unconventional methods 

 which might stain the granules of a sixth 

 cell type not revealed by conventional 

 methods. 



B. HYPOPHYSEAL RESPONSES TO ADRENAL 

 ABLATION 



Many reports of the cytologic changes 

 observed after bilateral adrenalectomy have 

 been published. Some observers have not re- 

 marked on any extensive alteration. Thus, 

 Nicholson (1936) did not observe any 

 change in the pars anterior of dogs after 

 bilateral adrenalectomy, and Koneff, 

 Holmes and Reese (1941) found that in rats 

 to which sodium chloride was administered 

 after adrenalectomy, cytologic changes were 

 minimal. Houssay (1952) also remarked 

 that in strains of rats which survive in good 

 condition after adrenalectomy there is little 

 hypophyseal disturbance compared with 

 those which have severe insufficiency symp- 

 toms. 



It therefore seems that the increased 

 secretion rate or the depletion of the adreno- 

 corticotrophin content of the hypophysis 

 which follows adrenalectomy need not be 

 accompanied by any marked change in the 

 appearance after staining by the customary 

 methods. 



Certain changes in the acidophil and 

 basophil cells which are observed in certain 

 strains of rats after adrenalectomy, if ad- 

 ditional salt is not administered, must be 

 related to the extensive metabolic disturb- 

 ances produced by the adrenal insufficiency. 

 These changes have been described by 

 Reese, Koneff and Akimoto (1939) . Changes 

 in the acidophil cells consist of degranula- 

 tion with a diminution in the size and 

 number of cells. The Golgi body in these 

 regressing acidophils is transformed from 

 the usual acidophil form which envelops 

 half the circumference of the nucleus into 

 a concentrated spherical or oval body. 

 These changes indicate decreased activity. 

 Cells of the basophil class also show exten- 

 sive degranulativc changes with reduction 

 in size and number, but some basophil cells 

 with enlarged Golgi bodies are seen, espe- 

 cially at short intervals after adrenalec- 

 tomy. Tuchmann-Duplessis (1953) also 

 found that, although most of the basophil 

 cells undergo degenerative changes after 



