ESTROGEN AND PROGESTERONE 



565 



These ingenious experiments will be referred 

 to often in the course of our discussion but 

 at present the response of endometrial 

 transplants in the eye to estrogen is of pri- 

 mary interest. 



Monkeys having ocular transplants were 

 given 200 to 300 R.U. of estrone daily for 

 about 1 to 3 months. The transplants did 

 not grow to a certain size and then remain 

 stationary, but instead periods of rapid 

 growth were interrupted by periods of re- 

 gression which usually involved a marked 

 decrease in size, and if regression was ex- 

 tensive and rapid, bleeding ensued. It also 

 was found that these episodes of regression 

 in the transplants were usually accompanied 

 by a decrease in the size of the uterus. 



Comparisons between the results of these 

 experiments and those we have discussed 

 previously may be misleading since it seems 

 that only 1 of the 5 animals (no. 295) used 

 was castrated. Also, the dosage of estrogen 

 was not sufficient to maintain the endome- 

 trium of the uterus for an indefinite period 

 without bleeding and this also was reflected 

 in the transplants. It seems questionable 

 that the growth capacity of endometrial 

 transplants in the eye can be determined un- 

 less sufficient estrogen is given to prevent 

 bleeding in the uterus. Therefore, it would 

 seem that these experiments contribute less 

 to an analysis of the effects of estrogen on 

 endometrial growth than they do to an un- 

 derstanding of the events that precede and 

 accompany menstruation. 



In summary, it seems clear that the out- 

 standing effect of estrogen on the uterus of 

 the monkey is one of growth (Allen, 1927, 

 1928). The involuted uterus of a castrated 

 animal can be restored to its normal size in 

 2 or 3 weeks by daily injections of adequate 

 amounts of estrogen. At this time there is an 

 increase in vascularity, a clear-cut hyper- 

 emia as seen in rodents. There also is secre- 

 tion of luminal fluid (Sturgis, 1942) but this 

 does not distend the uterus as in the mouse 

 and rat. This is accompanied by an increase 

 in tissue fluid, especially in epithelial tissues 

 (surface epithelium and glands) , and in the 

 connective tissue of the stroma. Glycogen 

 may be present at the basal ends of epithe- 

 lial cells beneath the nuclei (Overholser and 

 Nelson, 1936) but it apparently is not read- 

 ily released under the action of estrogen 



alone (Lendrum and Hisaw, 1936; Engle 

 and Smith, 1938) . The glands of the endo- 

 metrium maintain a straight tubular struc- 

 ture with some branching near the muscle 

 layers. The condition produced experimen- 

 tally in the monkey's uterus by short term 

 treatments with estrogen is equivalent to 

 that present in the normal animal at mid- 

 cycle, or even a few days later if ovulation 

 does not occur. 



If, however, an estrogen treatment is con- 

 tinued for several months conditions de- 

 velop in the uterus that are not found 

 during the follicular phase of a normal men- 

 strual cycle. When the daily dose of estrogen 

 is small menstruation occurs at intervals 

 during the treatment (Zuckerman, 1937b) 

 and probably marks periods of endometrial 

 regression as observed by Markee (1940) in 

 eye transplants, but if the dosage is in- 

 creased by a sufficient amount (about 10 

 /xg. estradiol- 17/3 daily) injections may be 

 continued for a year or longer without 

 bleeding. Although the size of the uterus re- 

 mains within the range of normal variation 

 as the injections are continued, the myome- 

 trium tends to increase in thickness and the 

 endometrium becomes thinner, a condition 

 not corrected by further increases in dosage 

 or by prolonging the treatment. The cause 

 responsible for the limited response of the 

 endometrium under these conditions is not 

 known but apparently is not a restrictive in- 

 fluence of the myometrium as similar re- 

 sponses are given when the endometrium is 

 exposed by incising the uterus, in abdominal 

 fistulae, and in exteriorized uteri. 



III. Effects of Progesterone 

 on the Uterus 



It has been mentioned that a menstrual 

 cycle, in which ovulation occurs, can be con- 

 veniently divided into a follicular and a 

 luteal phase. The follicular phase extends 

 from menstruation to ovulation and the 

 luteal phase from ovulation to the following 

 menstruation. It has been shown in the 

 previous discussion that the endometrial 

 modifications characteristic of the follicular 

 phase of the cycle can be duplicated in a 

 castrated monkey by the injection of estro- 

 gen. Likewise, the progestational condition 

 characteristic of the luteal phase can be de- 

 veloped by giving progesterone. In fact, all 



