MAMMALIAN REPRODUCTIVE CYCLE 



509 



B. CYCLIC MANIFESTATIONS AFTER 

 OVARIECTOMY OR HYPOPHYSECTOMY 



Residual cyclic changes in the vagina 

 liave been reported in ovariectomized mice 

 (Kostitch and Telebakovitch, 1929) and 

 rats (Mandl, 1951). The periodicity is very 

 nearly that of the normal cycles, at least in 

 the latter species. Vaginal cycles of similar 

 duration with more extreme estrous changes 

 are found in ovariectomized rats receiving 

 daily injection of threshold doses of estro- 

 gens (del Castillo and Calatroni, 1930; 

 Bourne and Zuckerman, 1941). The same 

 was remarked in mice by Emmens (1939) 

 and a report by Veziris (1951) indicates 

 that vaginal periodicity may obtain in cas- 

 trated or menopausal women receiving es- 

 trogen. Although sucli events have been 

 called ''threshold cycles," the term may 

 simply express the fact that they are most 

 easily recognized when estrogen is given at 

 threshold level. Hartman (1944), employing 

 a modified Shorr stain for vaginal smears, 

 found that castrated rats given large 

 amounts of estrogen daily (5 to 100 fig. es- 

 tradiol dipropionate) displayed complete 

 cornification at 4- to 5-day intervals. Dur- 

 ing the time intervening there was admix- 

 ture of Shorr cells, smaller epithelial cells, 

 and leukocytes. 



Analogous phenomena have been recog- 

 nized in the endometrium of castrated mon- 

 keys (Zuckerman, 1937, 1941) injected daily 

 for as long as 1 year with threshold doses of 

 estrone (10 fig.). Larger doses prevent cyclic 

 bleeding (see Hisaw, 1942). From the report 

 of Veziris (1951) it may be judged that 

 threshold endometrial cycles also occur in 

 women and that the vaginal and endo- 

 metrial cycles are synchronized in consider- 

 able extent. 



Full explanation of these phenomena is 

 not at hand. From the standpoint of the 

 present discussion certain considerations are 

 especially noteworthy. (1) Vaginal "thresh- 

 old cycles" have been obtained in castrated 

 rats in the absence of either hypophysis or 

 adrenals (Bourne and Zuckerman, 1941 ; del 

 Castillo and di Paola, 1942) . The former au- 

 thors encountered the phenomenon in two 

 rats from which both the hypophysis and 

 adrenals had been removed. It is important 



to remember, however, that the pars tu- 

 beralis remains in situ after the usual hy- 

 pophysectomy procedure, that accessory 

 adrenocortical tissue is frequent in rats, and 

 that gonadal rests might remain unrecog- 

 nized. (2) The reported lengths of vaginal 

 and endometrial cycles agree favorably with 

 the cycle lengths in intact individuals of the 

 respective species. The degree of conformity 

 between vaginal and uterine cycles indi- 

 cated by Veziris {loc. cit.) suggests some 

 sort of integrating mechanism. Much more 

 information is required, however, before one 

 may reject the alternative view that rhyth- 

 mic activity is an innate characteristic of 

 these organs. 



C. CYCLIC MANIFESTATIONS IN THE ABSENCE 

 OF OVARIAN FOLLICLES 



Many years ago Parkes (1926a, b) and 

 Brambell, Parkes and Fielding (1927a, b) 

 reported vaginal and uterine cycles in mice 

 in which the entire follicular apparatus had 

 been destroyed by x-radiation. Schmidt 

 (1936) described the phenomenon in the 

 guinea pig, noting that, although most of 

 her estrous animals had one or more large 

 atretic or cystic follicles, as she had earlier 

 reported (Genther, 1931), a few animals 

 exiiil)ited periodic vaginal opening of short 

 duration and correlated proestrous vaginal 

 smears, in the absence of follicles. Her as- 

 says of urinary estrogen were negative in 

 these animals, unlike the positive assays in 

 those in which one or more follicles were 

 demonstrable. Attempts by several workers 

 (Drips and Ford, 1932; Levine and Witschi, 

 1933; Mandel, 1935) to reproduce in rats 

 the results that Parkes and Brambell had 

 found in mice, were unsuccessful, a fact in- 

 dicating no estrogenic activity in ovaries 

 completely lacking follicles and ova. Parkes 

 (1952) more recently returned to this prob- 

 lem, reporting vaginal cycles and "fully 

 functional" uteri in castrated rats bearing 

 grafts of ovaries in which all organized folli- 

 cles and ovocytes had been destroyed by 

 deep freezing. These were true estrous cy- 

 cles, in the sense that the animals would 

 mate. 



Many questions are posed by these ob- 

 servations. The fundamental one seems to 

 be whether these cycles express periodicity 

 of hypophyseal gonadotrophin secretion. 



