GONADOTROPIC SUBSTANCES 



al animals to the same dose of prolan may be extraordinarily 

 variable. Doses approaching the liminal tend to produce 

 chiefly follicle growth; larger doses also cause hemorrhage 

 into follicles and the formation of corpora lutea atretica. 

 Ovulation^ may be produced under appropriate conditions, 

 but usually does not follow the injection of prolan as it is 

 ordinarily given. The cells of the theca interna, and to a less- 

 er extent of the membrana granulosa, enlarge, proliferate, 

 and take on the appearance of lutein cells in the later stages 

 of the ripening of the follicle (or, under some conditions, with- 

 out follicular growth). At this time blood may be extravas- 

 ated into the follicular cavity.'" Finally, corpora lutea well 

 supplied with blood vessels are formed. Such corpora lutea 

 are usually atretic. 



The striking changes here described may be observed in 

 immature mice after the administration of prolan for only a 

 few days. However, the character and degree of the altera- 

 tions produced vary with the size of the total dose and the 

 manner in which it is distributed. Zondek and Aschheim 

 (1928, 1930) ordinarily injected prolan six times within 48 

 hours and examined the genital tract about 100 hours after 

 the first injection. Brouha and Simmonet (1930) have given 

 an account of the effects of doses distributed differently. 



Associated changes occur in the fallopian tubes, uterus, and 

 vagina. During follicular growth, or later, all the phenomena 

 of oestrus such as hypertrophy of the uterus, distension of the 

 uterus with fluid, opening of the vaginal orifice, and cornifica- 

 tion of the vaginal mucous membrane may appear. Later, 

 when progesterone may be the chief ovarian secretion, both 

 the uterus and the vagina may assume the appearance of 

 dioestrus in the adult. 



'See the reports of Hill (1932) and Zondek (1932). 



'° Hemorrhagic follicles are not found in the ovaries of normal mice or rats. 

 However, they have been observed in the ovaries of other adult animals, e.g., the 

 rabbit. Also see the reports of Emanuel (1930), and Zondek (1931J. 



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