MAMMALIAN REPRODUCTIVE CYCLE 



531 



sence of the hypophysis. There is no evi- 

 dence for or against the lactogenic liormone 

 in this capacity, except in rats. 



Estrogens have direct hiteotrophic action 

 in the rabbit (Robson, 1937, 1938, 1947). 

 The effect does not depend on the hypophy- 

 sis and has been produced by impLantation 

 of estrogen crystals within corpora liitea 

 (Hammond, Jr., and Robson, 1951; Ham- 

 mond, Jr., 1952). Westman (1934) had ear- 

 lier shown that operative reduction of 

 ovarian stroma in pseudopregnant rabbits 

 results in corpus luteum regression and that 

 this can be prevented by administration of 

 estrogen. Corpora lutea induced by gonado- 

 trophin injection or by mating, as the case 

 may be, require the presence of the hypoph- 

 ysis for their continued function ( Smith and 

 White, 1931; Westman and Jacobsohn, 

 1936). Theoretically, then, in rabbits the 

 hypophysis liberates FSH and LH which act 

 on the interstitial tissue to cause estrogen 

 secretion. This in turn stimulates the cor- 

 pora lutea to secrete progesterone. 



The effect of estrogen on the corpora lutea 

 of rats is largely indirect and requires the 

 presence of the hypophysis. Massive dosage 

 with estrogen beginning soon after ovula- 

 tion results in the enlargement of the cor- 

 pora lutea and the production of sufficient 

 amounts of progesterone to mucify the vagi- 

 nal mucosa (Selye, Collip and Thomson, 

 1935; Wolfe, 1935; Desclin, 1935; Merckel 

 and Nelson, 1940). In fact, a single injec- 

 tion of 50 /Ag. estradiol bcnzoate on the day 

 after ovulation is sufficient to cause pseudo- 

 pregnancy. These effects are now judged to 

 be the result of induced liberation of hy- 

 pophyseal luteotrophin. vSimilar effects have 

 been reported after administration of an- 

 drogens (McKeown and Zuckerman, 1937; 

 Wolfe and Hamilton, 1937; Freed, Greenhill 

 and Soskin, 1938; Laqueur and Fluhmann, 

 1942). 



Desclin (1949b) stated that in hypophy- 

 sectomized rats the administration of estro- 

 gen augments the hiteotrophic action of 

 lactogen, producing functional corpora lu- 

 tea in the presence of subthreshold doses of 

 the latter hormone. A physiologic synergism 

 of the two substances has thus been indi- 

 cated. Mayer (1951) suggested that this 

 may explain the stimulation of corpora lutea 

 of lactation which follows estrogen treat- 



ment in this species. Greep and Chester 

 Jones (1950) postulated that estrogen fa- 

 vors corpus luteum function in the rat by 

 causing the luteal cells to produce choles- 

 terol as a precursor of progesterone. Their 

 actual data, however, indicate that the in- 

 crease of visible cholesterol after estrogen 

 treatment was confined to the interstitial 

 tissue. 



Factors responsible for cholesterol storage 

 and mobilization in corpora lutea of the rat 

 were analyzed by Everett (1947). In hy- 

 pophysectomized rats in which corpora lutea 

 were maintained by lactogen the injection 

 of pituitary LH induced the storage of 

 cholesterol, but this effect did not occur in 

 hypophysectomized rats in the absence of 

 lactogen. It could be induced during preg- 

 nancy or pseudopregnancy by estrogen if 

 the hypophysis remained in place. Addition 

 of an excess of lactogen prevented choles- 

 terol storage. Lactogen thus tends to deplete 

 cholesterol content of rat luteal tissue as 

 ACTH tends to deplete adrenocortical cho- 

 lesterol. 



2. ''XonfunctionaV' Corpora Lutea 



In the short cycles of the rat, mouse, 

 hamster, and so on, the corpora lutea are 

 commonly said to be nonfunctional. The 

 meaning of this statement, of course, is that 

 they are incapable of supporting a decidual 

 reaction (Long and Evans, 1922), or of lire- 

 venting ovulation. They need not be totally 

 inactive, however, to fail to cause these 

 manifestations. Whereas daily injection of 

 1.5 mg. or more of progesterone into intact 

 female rats will simulate pseudopregnancy 

 and indefinitely delay ovulation (Selye, 

 Browne and Collii^, 1936; Phillips, 1937), 

 smaller amounts of 1.0 rag. or less are com- 

 patible with the short cycle (Lahr and 

 Riddle, 1936; Phillips, 1937; Everett, 1940a, 

 b; and unpublished). In the absence of es- 

 trogen in castrated females, daily injection 

 of as little as 0.25 rag. progesterone will sup- 

 port deciduomata (Velardo and Hisaw, 

 1951). Very small amounts of estrogen aug- 

 ment this action of progesterone (Rothchild, 

 Meyer and Spielman, 1940) but somewhat 

 larger amounts are inhibitory unless the 

 progesterone dose is proportionately in- 

 creased (Velardo and Hisaw, 1951). In the 

 intact animal the progestational effects of 



