96 INTERNAL SECRETIONS OF THE OVARY 



amount may be required to produce it, and therefore that 

 greater accuracy can be obtained. The prooestrous smear is, 

 however, much more hkely to be confused with variations of the 

 smear as found during operative dioestrus than is the clear-cut 

 oestrous smear. For this reason the use of the prooestrous smear 

 only is to be deprecated, especially, as Allen and Doisy remark, 

 in new qualitative work. 



Another complication in the use of the vaginal reaction as a 

 test of oestrus-producing activity is the question of whether a 

 dose which will cause oestrous symptoms in the vagina will also 

 produce them in the uterus. In other words, is the threshold 

 value the same for the vagina as for the other accessory organs? 

 Examination of the smear found during induced oestrus in the 

 ovariectomized animal reveals many cases where, though true 

 cornification has occurred, the reaction is hardly as strong 

 as is found during oestrus in the normal animal. Correlated 

 with this it is possible to observe many cases where a definite 

 vaginal reaction has occurred without the slightest trace of an 

 oestrous condition in the uterus. This seems to show fairly 

 definitely that the vaginal reaction has a lower threshold value 

 than has the uterine. Brouha and Simonnet (96) state that the 

 vaginal reaction may be induced without the uterine changes in 

 immature females, and the absence of mating instinct in adults 

 is also attributed to a different threshold requirement of oestrin. 

 In the writer's experience, however, even excessive doses do not 

 result in copulation. 



A more serious difficulty has recently become evident in the 

 use of the vaginal smear technique. The cornification of the 

 vagina of the rat, mouse, and guinea-pig was originally thought 

 to be absolutely specific for oestrus, especially since attempts 

 to produce cornification in test animals with various non- 

 specific substances have had negative results. Thus, Robin- 

 son and Zondek (538) obtained no result from injection of 

 choline, arginine, guanidine, tyrosine, tyramine, alanine, and 

 asparagine. These authors found, however, that histamine 

 and adrenalin produced hyperplasia of the uterus, but Levin 

 (361) showed that no cornification is produced by the former 

 substance. Frank and his co-workers (230) obtained nega- 

 tive results from olive oil and linseed oil, while yohimbin 



