MAMMALIAN REPRODUCTIVP] CYCLE 



535 



local anesthesia of the vagina and cervix by 

 cocaine or procaine prevented the response 

 to sterile copulation in 23 of 35 rats. 



Removal of neocortex (Davis, 1939) did 

 not interfere with the pseudopregnancy re- 

 sponse to electrical stimulation of the cer- 

 vix, although there was slight impairment of 

 the response to mechanical stimulation or 

 sterile mating (single-plug?). 



These results taken together have been 

 construed to mean that induction of pseudo- 

 pregnancy in rats involves a reflex similar to 

 the ovulation reflex in rabbits. Certain con- 

 siderations, however, raise the possibility 

 that it may not be a "trigger" stimulus to 

 the hypophysis as long believed (Everett, 

 1952a). In the first place, it seems doubtful 

 that a trigger stimulus would result in con- 

 tinuation of a new pattern of secretion 

 (luteotrophin) for as long as 10 to 12 days. 

 Furthermore, as noted above, cervical stim- 

 ulation during the diestrum preceding ovu- 

 lation may induce pseudopregnancy (Greep 

 and Hisaw, 1938). Similarly, copulation 

 during a cycle in which ovulation is blocked 

 by pentobarbital results in a pseudoi)reg- 

 nancv that begins after the next estrus (Fig. 

 8.12)^. 



We turn now to experiments concerned 

 directly with the hypothalamo-pituitary 

 system and pseudopregnancy. Westman and 

 Jacobsohn (1938c) cut the pituitary stalks 

 of estrous female rats. Barriers of metal foil 

 were inserted to prevent regeneration of 

 nerve fibers assumed to innervate the adeno- 

 hypophysis. Regeneration of blood vessels 

 must have been equally impossible. Controls 

 were simply hypophysectomized. Two to 5 

 hours after the operations electrical stimu- 

 lation of the cervix was administered to all 

 animals. Pseudopregnancies were demon- 

 strated by deciduomas in traumatized uteri 

 of all the stalk-sectioned animals but not in 

 the completely hypophysectomized rats. 

 Desclin (1950) reported the maintenance of 

 pseudopregnancy in estrogen-treated rats 

 in which the only remaining hypophyseal 

 tissue was in the form of grafts in the kid- 

 ney. Whereas in hypophysectomized con- 

 trols the estrogen treatment (stilbestrol pel- 

 lets) produced cornification of the vagina 

 and no enlargement of corpora lutea, the en- 

 grafted-estrogenized rats developed muci- 

 fied vaginas and enlarged corpora lutea as 



in intact rats similarly treated with estro- 

 gen. Desclin concluded that the grafted hy- 

 pophysis is able to respond to estrogen by 

 liberating luteotrophin. 



It is now apparent, however, that neither 

 cervical stimulation nor estrogen treatment 

 is needed to invoke pseudopregnancy when 

 the gland is isolated from the hypothalamus 

 (Everett, 1954, 1956a; Nikitovitch-Winer 

 and Everett, 1958a; Sanders and Rennels, 

 1957; Desclin, 1956a, b). When autografts 

 of anterior hypophysis were made to the re- 

 nal capsule or near the common carotid 

 artery on the day after ovulation in adult 

 cyclic rats, corpus luteum function was in- 

 voked and maintained without any stimu- 

 lus other than the operative procedures 

 themselves. In short-term experiments in 

 which the uteri were traumatized 4 days 

 after the transplantation large deciduomas 

 were regularly found at 8 days in the proven 

 absence of residual hypophyseal tissue at 

 the original site (Everett, 1954). Hypophy- 

 sectomized controls were negative. In long- 

 term experiments, continuing luteal function 

 was demonstrated for as long as 3 months. 

 Here the test for luteal function was vaginal 

 mucification in the presence of massive 

 amounts of estrogen administered during 

 the final week of the experiment (Everett, 

 1956a). Controls in which the grafts or the 

 ovaries were removed at the beginning of 

 such estrogen treatment responded with full 

 vaginal cornification. Follicular apparatus 

 and interstitial tissue of the ovaries atro- 

 phied promptly after the grafting opera- 

 tions, whereas corpora lutea forming at that 

 time were maintained for the long periods 

 without histologic sign of deterioration. In 

 later work, the decidual reaction was used 

 as the test for luteal function, positive re- 

 actions being elicited as late as 2 months 

 after the transplantation. It was discovered 

 that function of the graft is not influenced 

 by stage of the cycle at which transplanta- 

 tion is carried out and that grafts in the 

 anterior chamber of the eye secrete luteo- 

 trophin like those on the kidney (Nikito- 

 vitch-Winer and Everett, 1958a). Trans- 

 section of the pituitary stalk is sufficient 

 in itself to provoke pseudopregnancy. If an 

 effective barrier to vascular regeneration is 

 inserted, the pseudopregnancy will heorve 

 permanent, but otherwise it will l:i •■ i;!*' 



