574 



PHYSIOLOGY OF GONADS 



endometrium (Hellman, Rosenthal, Kistner 

 and Gordon, 1954) and granulosa-cell tu- 

 mors of the ovary. Various degrees of meta- 

 plasia may occur in the cervix during preg- 

 nancy both in the mother and newborn but 

 Fluhmann (1954) did not find it as fre- 

 quently as in nonpregnant women. 



This reaction to estrogen as seen in the 

 cervix of castrated monkeys is initiated by 

 growth of small undifferentiated cells below 

 the columnar mucous cells of the secretory 

 epithelium. Fluhmann (1954) suggests that 

 these cells are really undifferentiated cells 

 of the cervical mucosa which have the po- 

 tentiality of becoming columnar or squa- 

 mous or simply undergoing multiplication 

 and remaining as indifferent or reserve cells. 

 These cells accumulate, in response to es- 

 trogen, to form aggregates of several cells 

 in thickness and, although this may occur in 

 any area of the endocervix, it is generally 

 more pronounced below the base of the 

 glands. As this process proceeds the colum- 

 nar mucous cells are pushed outward and 

 are finally desquamated thus exposing the 

 underlying metaplastic cells to the lumen of 

 the gland (Fig. 9.20). 



Fig. 9.20. Al.iaph 



in a castrated monkey that li.-id rci-civcd 1 nig. 

 estriol daily for 48 days. 



The cells of these lesions undergo a char- 

 acteristic differentiation. When first formed 

 they are small, cuboidal, and have spheri- 

 cal nuclei with dense chromatin. As they in- 

 crease in number those in the center of the 

 cellular mass become larger and acquire an 

 eosinophilic cytoplasm. Such collections, as 

 seen at the base of the cervical glands, may 

 grow in height and form cone-shaped masses 

 with the apexes protruding through the mu- 

 cous epithelium into the lumen or they may 

 remain as more or less compact structures. 

 This difference in growth seems to have a 

 general relation to the dosage of estrogen. 

 Large doses cause more rapid growth and 

 cone formation with the loss of cells from 

 the apex either singly or in groups, whereas 

 small doses produce slower growth and des- 

 quamated cells are seldom seen in the lu- 

 men. However, regardless of the rate of 

 growth, the cells at the base of the lesion 

 remain undifferentiated and continue as the 

 principal area of cell proliferation. 



Pearl formation is occasionally seen and 

 may be quite common in animals on low 

 dosages of estrogen. Under strong estrogenic 

 stimulation and consequently rapid growth, 

 these structures apparently are desqua- 

 mated before they are completely formed. 

 However, very early stages are frequently 

 seen and may even be present in small 

 clumps of metaplastic cells, but they are 

 more commonly found in the larger collec- 

 tions at the base of the glands. Their ap- 

 pearance is initiated by swelling and dis- 

 integration of one or more adjacent cells 

 that form a center around which epidermidi- 

 zation takes place. Further development 

 does not proceed under the influence of es- 

 ti'ogen, beyond the formation of a small cen- 

 tral cavity. 



The most conspicuous difference between 

 the metaplastic growths produced by estro- 

 gen and true cancer of the cervix in the 

 monkey (Hisaw and Hisaw, Jr., 1958) is 

 that the former remain noninvasive even 

 when the treatment is continued well over 

 a year. They also involute when the treat- 

 iiiciit is discontinued and they do not ap- 

 peal' when progesterone is given simultane- 

 ously with estrogen. When the injections of 

 progesterone are started after metaplastic 

 growths have been formed in response to 

 estrogen, further growth is inhibited and 



