MAMMALIAN REPRODUCTIVE CYCLE 



529 



piiU' injections in the midst of the critical 

 period (Everett and Sawyer, 1953; Everett, 

 1956b L Unlike the trigger-like stimulus in 

 rabbits, that in rats is prolonged to about a 

 half-hour. In different individuals the stim- 

 ulus begins at different times, (Fig. 8.11 L 

 Release of LH is probably coextensive with 

 the stimulus. In parallel experiments carried 

 out at various times during the critical 

 period, groups of proestrous rats w^ere hypo- 

 physectomized and other similar groups 

 were injected with atropine. The two pro- 

 cedures gave essentially the same results, 

 as measured on the following morning by 

 the proportionate numbers of rats in which 

 ovulation w^as found blocked or partially 

 blocked (Everett, 1956b). The time interval 

 from stimulation of the hypophysis to ovu- 

 lation is 10 to 12 hours in rats (Everett, 

 Sawyer and INIarkee, 19491. thus ai)out 

 the same as in rabbits. 



D. PERSISTENT FOLLICLE 



The state of persistent follicle may be 

 considered as one in which for some reason 

 there is a physiologic blockade of the hypo- 

 thalamic ovulating stimulus. In the rabbit 

 one may attribute failure of ovulation to 

 absence of reflex stimulation, on the one 

 hand, and a relatively high threshold of the 

 hypothalamo-pituitary apparatus for estro- 

 gen and progesterone, on the other. In the 

 rat certain conditions {e.g., continuous il- 

 lumination) elevate the threshold of the 

 hypothalamo-pituitary system, with the 

 result that persistent estrus and jicrsistent 

 follicle occur (Hemmingsen and Krarup, 

 1937; Browman, 1937; Everett, 1940a; 

 Dempsey and Searles, 1943). Additional 

 stimulation, furnished by either progester- 

 one or coitus, is necessary to overcome this 

 blockade. 



An age factor is operative in the spon- 

 taneous onset of persistent follicle in old 

 female rats. This condition is well recog- 

 nized as an occasional occurrence (Evans 

 and Long, 1921 ; Doling, Blandau, Rundlett 

 and Young, 1941 ; Marvin and Meyer, 1941 ; 

 Hartman, 1944). In the DA strain (Everett, 

 1939-1944) the age of onset was unusually 

 early in segregated females under normal 

 lighting conditions, i.e., about 150 days of 

 age which was more than 200 davs earlier 



than in a normal strain. In Fi hyljrids the 

 age of onset was intermediate. This factor, 

 ill defined though it is, is also expressed in 

 sensitivity to continuous illumination. Post- 

 pubertal rats of the normal strain in contin- 

 uous light continued to experience regular 

 cycles for as long as 40 days, whereas older 

 animals (200 to 250 days) began to show 

 persistent estrus within 10 days. Postpuber- 

 tal DA rats, on the other hand, responded 

 as promptly as 250-day-old normal rats. 

 Hybrids again were intermediate. It was 

 also found in older DA rats that had spon- 

 taneously developed persistent estrus under 

 a lighting schedule of 14 hours per day, that 

 reduction of the light ration to 9 hours usu- 

 ally restored cyclic function. It seems, then, 

 that the age factor in cjuestion intensifies 

 the effect of a given amount of daily il- 

 lumination. 



Interference with ovarian cii'culation in 

 rats causes persistent follicle and failure 

 of luteinization. This effect has been re- 

 ported after ligation of the pedicle (Fels, 

 1952) , ligation of the oviduct with resultant 

 increase of pressure within the ovarian cap- 

 sule (Haterius, 1936; Navori, Fugo and 

 Davis, 1952), hysterectomy with increased 

 pressure (Bradbury, Brown and Gray, 

 1950), and transplantation of the ovary to 

 the tip of the tail (Hernandez, 1943; Biels- 

 chowsky and Hall, 1953). A possible expla- 

 nation of this result is that the diminished 

 blood flow releases insufficient estrogen 

 to reach the threshold of the LH-release 

 mechanism. An alternative explanation may 

 l)e a change in the character of the secretory 

 product of the ovary. "Cystic" changes 

 of the ovaries are not uncommon after pel- 

 vic surgery in women. 



The occurrence of persistent follicle in 

 rats following partial nephrectomy (Diaz, 

 1940) has never been explained. It seemed 

 to be correlated with the development of 

 high blood pressure. Hence it may be allied 

 with the experiments just described. 



Pfeiffer (1936, 1937) reported that when 

 testes are temporarily grafted into female 

 rats during early infancy and removed be- 

 fore puberty the host animals exhibit con- 

 stant estrus after reaching maturity. The 

 same phenomenon has been observed after 

 postnatal treatment with testosterone or 



