THE HORMONE OF PREPARATION 



sociated with the phenomena of estrus. The pioneer American 

 worker, Leo Loeb, said in 1917 that some of the cyclic changes 

 in the uterus might be due to a secretion of the follicles. 

 Arthur Robinson of Edinburgh in 1918 went so far as to 

 write "It can scarcely be doubted that the phenomena of heat 

 are due to something produced by the follicles." Edgar Allen 

 now had the added evidence of the vaginal cycle pointing him 

 in the same direction. Enlisting the collaboration of Edward 

 A. Doisy, then a young biochemical colleague at Washington 

 University (St. Louis), he proceeded to test this hypothesis 

 by injecting a few drops of fluid, drawn from mature follicles 

 of the sow, under the skin of castrated female rats and mice. 

 In such animals, of course, cycles do not occur, and the 

 vaginal lining becomes very thin and undeveloped and remains 

 unchanged from day to day. An injection of follicle fluid, 

 however, produced in 48 hours a typical estrous condition of 

 the vagina, which could be easily detected by scraping or 

 washing out the vagina and looking at the cells under the 

 microscope. This result is shown in Plate XV, originally 

 published in illustration of Allen and Doisy's earliest results. 

 When administered to infantile rats and mice, the injections 

 caused the uterus to grow to adult size and the vagina to open 

 as in sexually mature animals (see Plate XVI, illustrating 

 similar growth of the uterus in monkey and rabbit). 



This astonishing result provided at once a new test, simple, 

 precise, and rapid, by which the chemists could follow the 

 hormone through various steps as they attempted to purify it. 

 A sample suspected to contain it can be injected into a cas- 

 trated rat or mouse and the vaginal cells examined under 

 the microscope at intervals until the estrous change is seen. 

 By giving graded doses to a series of animals the amount of 

 hormone in a sample can be measured. 



Follicle fluid is a complicated mixture of water, salts, a 

 little fat, a lot of protein. Doisy faced the task of extracting 

 from this "soup" a substance that could be present, as he 



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