THE (ESTRUS-PRODUCING HORMONE loi 



ovary, capsule, hilum, and Fallopian tube. These authors 

 reported that in 121 double-ovariectomized mice, all of which 

 showed initial cessation of the oestrous cycle, eleven subse- 

 quently showed signs of spontaneous oestrus. In eight of these 

 animals the presence of new ovarian tissue was demonstrated 

 histologically, but its exact source was not definitely found. 

 Regeneration Vv^as found to occur up to many months after 

 ovariectomy. These authors conclude {a) that regeneration 

 can best be detected by the spontaneous reappearance of 

 cestrus, (b) that adequate observation for such spontaneous 

 oestrus should be made between each experimental injec- 

 tion, and (c) that any anomalous test should be repeated 

 on another animal, and the first one examined for ovarian 

 regeneration. 



Hanson and Heys (269) have recently found regeneration in 

 5^0 of ovariectomized rats in which the completeness of the 

 original operation was checked by histological examination of 

 the ovaries removed. 



{e) STANDARDIZATION 



The unit. The unit of oestrin was originally considered to be 

 the amount required to produce full oestrous symptoms in an 

 ovariectomized animal, and a great deal of the initial standard- 

 ization was carried out on these lines. This technique amounted 

 to giving graduated doses to a series of animals, usually mice or 

 rats, the least amount causing oestrus being considered as the 

 unit. Recentty, however, attention has become directed to the 

 extraordinary individual variation in reaction which is found. 

 Two mgms. of a preparation may cause one mouse to come into 

 oestrus, whereas three mgms. may fail to produce this result in 

 another individual. This variation tends to invalidate any such 

 definition of the unit as that given above. Such variation, 

 however, is typical of the pharmacological reaction of animals to 

 many substances, and a method for dealing with the difiiculty 

 has now been extended by Coward and Burn (146) to the assay 

 of oestrin. This technique depends on the fact that if a group of 

 animals are injected, the number responding will increase as the 

 amount given increases. Coward and Burn found, for instance. 



