ESTROGEN AND PROGESTERONE 



567 



be maintained by continuing the progester- 

 one treatment, and involutionary processes 

 set in and the endometrium is reduced to a 

 thin structure. Yet, such degenerate endo- 

 metria are dependent upon progesterone 

 and will bleed within about 48 hours if the 

 injections are stopped. It also was found 

 that after discontinuence of progesterone 

 daily injections of 10 /i.g. estradiol may not 

 prevent bleeding. 



IV. Synergism between Estrogen 

 and Progesterone 



There is considerable evidence that in 

 primates progesterone under normal condi- 

 tions rarely if ever produces its effects in the 

 absence of estrogen. Large quantities of es- 

 trogen are present in human corpora lutea 

 (Allen, Pratt, Newell and Bland, 1930) and 

 during pregnancy the placenta secretes es- 

 trogens as well as progesterone (Diczfalusy, 

 1953) . This apparently is a common feature 

 of primates, as indicated by the excretion of 

 estrogens in the urine of pregnant chimpan- 

 zees and rhesus monkeys (Allen, Diddle, 

 Burford and Elder, 1936; Fish, Young and 

 Dorfman, 1941 ; Dorfman and van Wa- 

 genen, 1941). Also, correlated with this is 

 the observation that estrogen and progester- 

 one when given concurrently produce a 

 greater effect on the uterus of castrated 

 monkeys than either alone (Hisaw, Greep 

 and Fevold, 1937; Engle, 1937; Hisaw and 

 Greep, 1938; Engle and Smith, 1938) and 

 that an ineffective dose of progesterone is 

 greatly potentiated by estrogen. This syn- 

 ergistic effect of the two hormones on the 

 uterus of monkeys is quite different from 

 their action on the uteri of laboratory ro- 

 dents and rabbits. In these animals the ef- 

 fects of progesterone can be inhibited quite 

 easily by a surprisingly small dose of es- 

 trogen (see chapter 7). 



The synergism between estrogen and pro- 

 gesterone in the promotion of endometrial 

 growth can be demonstrated to best advan- 

 tage under the conditions of some of the 

 physiologic preparations that have been dis- 

 cussed. For instance, it was shown (Fig. 

 9.5) that growth of the endometrium under 

 the influence of estrogen was not enhanced 

 by relieving muscle tension by a midline in- 

 cision through the anterior wall of the 

 uterus. Now, if a similar operation is per- 



FiG. 9.9. Uterus of a castrated monkey that re- 

 ceived 10 fig. estradiol and 1 mg. progesterone 

 daily for 18 days, at which time the uterus was 

 opened from fundus to cervix and most of the 

 endometrium of the anterior wall removed. The 

 incision was not closed and the treatment was 

 continued for an additional 20 days. (From F. L. 

 Hisaw, in A Symposium on Steroid Hormones, 

 University of Wisconsin Press, 1950.) 



formed on the uterus of a monkey that is 

 receiving 10 /tg. estradiol daily and the 

 treatment continued with the addition of a 

 daily dose of 1 mg. progesterone, there usu- 

 ally follows a rapid growth of endometrial 

 tissue out through the incision until by 

 about 3 weeks a mass is formed which ap- 

 proximates the size of the entire uterus (Fig. 

 9.9). If this experiment is repeated and the 

 same dosage of progesterone is given with- 

 out estrogen, there is no outgrowth of the 

 endometrium (Fig. 9.10). 



A similar synergistic action can be seen in 

 utero-abdominal fistulae. We have men- 

 tioned that estrogen does not cause excessive 

 growth of the endometrium under these con- 

 ditions. However, endometria that have 

 reached their maximal response to estrogen 

 will show a resumption of growth if 1 or 2 

 mg. progesterone are added daily to the 

 treatment. By the 4th or 5th day lobes of 

 blood-red endometrium begin to protrude 



