MAMMALIAN REPRODUCTIVE CYCLE 



537 



then act like the intact hypoiihysis of the 

 Miihlbock-Boot mouse. Such a view, un- 

 fortunately, continues to set apart species 

 in which the luteal phase is not spontaneous, 

 by suggesting that only in them are special 

 neui'al nieclianisnis involved. 



B. LUTEOLYTIC MECHANISMS 



By luteolysis we shall refer to corpus lu- 

 teum regression in any of its manifestations. 

 Supposedly the initial change is functional, 

 after which overt cytologic and histologic 

 changes appear, leading eventually to the 

 total loss of glandular tissue. Very likely 

 the initial stages are occult and only gradu- 

 ally reach recognizable proportions. Men- 

 tion was made earlier of the fact that in 

 women and monkeys the peak of gestagen 

 secretion is about midway between ovula- 

 tion and menstruation. In rats indirect evi- 

 dence from progesterone injection experi- 

 ments leads to the deduction that toward 

 the close of a pseudoi)regnancy gestagen 

 secretion must drop below the estrus-sup- 

 pressing level several days before estrous 

 changes appear in the vaginal smear (see 

 Fig. 8.8). A more al)rupt drop is reported 

 for the ewe l)etween the 16th and 17th 

 (last) days of the cycle (Edgar and Ronald- 

 son, 1958). 



Long-term experiments with pituitary 

 autotransplants indicate that at least in the 

 rat the life span of the corpus luteum is not 

 limited by intrinsic factors. Some agent (s) 

 of extra-ovarian origin must, therefore, be 

 res]5onsible for at least the initial luteo- 

 lytic changes. Various bits of information 

 suggest that the agent is associated with, if 

 not identical with, FSH and/or LH. Greep 

 (1938) noted that after hypophysectomy 

 in rats the daily injection of LH over a pe- 

 riod of 10 days caused the corpora lutea to 

 regress more rapidly than otherwise. Greep, 

 van Dyke and Chow (1942) later were un- 

 able to repeat this with a more highly puri- 

 fied LH C'metakentrin") , a fact suggesting 

 that the earlier material was effective be- 

 cause of impurity. During the short cycle 

 of the rat, luteolysis is interrupted by trans- 

 lilantation of the pars distalis (Everett, 

 1954; Nikitovitch-Winer and Everett, 

 1958a). Whatever regressive changes are 

 in progress at that moment are evidently 

 suspended forthwith. They are first appar- 



ent during the third day of diestrum and be- 

 come increasingly pronounced during pro- 

 estrum and estrus. In this connection, it 

 should be recalled that during late diestrum 

 and proestrum patches of cells undergoing 

 fatty necrosis are first recognizable histo- 

 logically (Boling, 1942; Everett, 1945). 



Why is it that, in the face of a continuing 

 supply of luteotrophin in the Miihlbock- 

 Boot preparation, or in intact animals in- 

 jected daily with lactogen (Lahr and Riddle, 

 1936; Aschheim, 1954), luteolysis sets in 

 during the 2nd week? The question ob- 

 viously cannot be answered from present 

 knowledge. Nevertheless, it is clear that the 

 pseudopregnancy that transpires when a 

 significant i)ortion of hypophyseal tissue 

 remains in normal relation to the hypo- 

 thalamus is far from the steady state of that 

 which becomes established by total re- 

 moval of the pars distalis to an extracranial 

 site. It is also apparent that the onset of 

 luteolysis may be postponed by such means 

 as hysterectomy or production of artificial 

 deciduomas (see p. 538). Furthermore, 

 during lactation-pseudoi)regnancies in rats, 

 Canivenc and Mayer (1953) prolonged lu- 

 teal function to 34 days by substituting suc- 

 cessive new litters of suckling young. This 

 technique should prove especially valuable 

 in experimental analysis of both luteo- 

 trophic and luteolytic mechanisms. 



Benson and Folley (1956) suggested that 

 lactogen secretion is activated by oxytocin, 

 inasmuch as its injection prevented the nor- 

 mal inv'olution of the mammary glands after 

 withdrawal of the litters from lactating rats. 

 This observation has been confirmed by 

 McCann, Mack and Gale (1958), who also 

 noted the interruption of lactation by le- 

 sions of the sui)raoi)tico-hyiiophyseal tract. 

 Selye and ]\lcKeown (1934) long ago found 

 that pseudopregnancy could be induced in 

 cycling rats by the introduction of a suck- 

 ling litter. Although all this is consistent 

 with the above-mentioned observation by 

 Canivenc and Alayer, other workers have 

 observed luteolytic effects of gonadotrophin- 

 free oxytocin administered to cycling dairy 

 heifers (Armstrong and Hansel, 1958). Fur- 

 thermore, Grosvenor and Turner (1958), 

 after first noting that the administration of 

 Dibenamine, atropine, or pentobarbital to 

 rats prevented the expected drop in assay- 



