MAMMALIAN REPRODUCTIVE CYCLE 



503 



mates the accepted sign is the first menstru- 

 ation ; in rats it is the opening of the vagina ; 

 in many animals it is the swelling and red- 

 dening of the genitalia heralding the initial 

 l^roestrum. In other eases, e.g., sheep, the 

 only clear indication may be the behavior 

 of the female toward the male. From these 

 facts it is readily apparent that any one 

 sign is employed simply because it happens 

 to be accessible to easy observation. Yet 

 the increasing output of estrogen, whether 

 steady or cyclic, affects many parts of the 

 organism at the same time. Furthermore, in 

 any one individual the threshold for ex- 

 l)ression of a given sign may be relatively 

 liigh with respect to that of some other 

 manifestation. Thus, in Hartman's mon- 

 keys (1932), some were noted in which des- 

 quamation of vaginal epithelium occurred 

 in wave-like manner for a long time before 

 menstruation. In others "menstrual" bleed- 

 ing occurred with regularity while the uterus 

 remained very small and A'aginal desqua- 

 mation was negligible. 



Hartman summarized the step-wise man- 

 ner of maturation of ovary and accessory 

 organs of the monkey during adolescence 

 or following amenorrheic episodes some- 

 what as follows. The color of the sex skin 

 may be the first to appear. A slight men- 

 strual flow usually takes place before des- 

 quamation of vaginal epithelium becomes 

 measurable. "More rarely there may be 

 one or more low desquamation cycles before 

 a bleeding is recorded. Whole cycles marked 

 liy jieriodic bleeding and some vaginal des- 

 quamation may occur before there is any 

 noticeable increase in size of the ovaries 

 and uterus. These organs increase also in a 

 saltatory manner, hence the term 'staircase' 

 phenomenon for the process. Finally, the 

 endocrines effect the acme of the reproduc- 

 tive process — ovulation." 



Individual variation in the degree of ab- 

 ruptness with which the first ovulation is 

 achieved is well illustrated in a study of 

 puljertal guinea pigs by Ford and Young 

 (1953). In most cases the first period of 

 vaginal opening was much longer than in 

 subsequent cycles. Whatever the duration, 

 ovulation was more closely related to the 

 end than to the beginning of the period, as 

 indicated by histologic study of ovaries. 



Even ovulation and corpus luteum for- 



mation do not signify that full power of 

 reproduction has arrived. For example, the 

 first cycle of the adolescent rat may culmi- 

 nate in ovulation without sexual receptivity 

 (Blandau and Money, 1943). In the ewe, 

 an ovulation without overt signs of heat 

 may at times take place during the anes- 

 trum, especially just before and just after 

 the breeding season (McKenzie and Terrill, 

 1936). The phenomenon is occasional in 

 ewes during the season and has also been 

 described in cattle (Hammond, 1946). In 

 fact, the full manifestation of estrus in 

 sheep seems to require the presence of a 

 "waning" corpus luteum (Robinson, 1951). 

 In sheep the transition from seasonal or 

 prepubertal anestrum to the breeding sea- 

 son may involve relatively minor changes 

 in hypophyseal activity. Even in the im- 

 mature rat both the hypophysis and the 

 ovary are capable of far greater secretory 

 function than they normally display. In the 

 equilibrium that prevails, the ovary ap- 

 pears to hold the upper hand by reason of 

 a low hypophyseal threshold at which estro- 

 gen suppresses gonadotrophin secretion in 

 the immature individual (Hohlweg and 

 Dohrn, 1932; Byrnes and Meyer, 1951b) 

 and a low ovarian threshold at which gona- 

 dotrophin stimulates estrogen secretion. 

 Byrnes and Meyer (1951a) reported that 

 suppression of hypophyseal gonadotrophin 

 content in immature rats can be accom- 

 plished with doses of estrogen much smaller 

 than those that affect uterine growth. It is 

 also known that the immature ovary can be 

 induced experimentally to secrete estrogen 

 by injection of amounts of gonadotrophin 

 that are too small to produce significant 

 increase of ovarian weight or follicle de- 

 velopment (Levin and Tyndale, 1937; Moon 

 and Li, 1952). When a gonadectomized im- 

 mature rat is united in parabiosis (Kallas, 

 1929, 1930 » with a normal or hypophysec- 

 tomized female littermate, precocious pu- 

 berty is induced in the latter animal because 

 insufficient estrogen passes to the first part- 

 ner to inhibit gonadotrophin secretion (see 

 Finerty, 1952). The somewhat analogous 

 experiment of transplanting ovaries to the 

 spleen produces ovarian hypertrophy in 

 much the same way. Here again, it is 

 thought that the hypophysis becomes hyper- 

 active because the amount of estrogen 



