GESTATION 



991 



nificant change in cell voluiiic was obtained. 

 The estradiol-induced anemia is both nor- 

 mochromic and normocytic and is caused by 

 a htMnodilution. However, in addition to the 

 ciianges in the blood and plasma volumes, 

 estradiol induces a significant increase in 

 the thiocyanate space. Furthermore, only 

 the massive dosage of 1.0 mg. estradiol per 

 day elicits an anemia comjKirable to that 

 observed in pregnancy. This dosage level 

 is probably toxic since there is a decrease 

 in the body weight of most rabbits which re- 

 ceived this treatment. Thus, in spite of 

 the similarities of these anemias, it is 

 likely that estrogen is not the sole etiologic 

 agent in the anemia of pregnancy. 



Progesterone alone at dosages of 4 mg. 

 daily has little effect on the plasma volume 

 or the thiocyanate space. This steroid does 

 exert a significant influence on the action 

 of estradiol on the blood and plasma vol- 

 ume, but it is to be noted that rather large 

 dosages of estradiol were still needed to in- 

 duce a significant hypervolemia and that 

 the effect depends on the ratio of the con- 

 centration of the two hormones. The hyper- 

 volemia induced by the treatment with 4 

 mg. progesterone in combination with 0.1 

 mg. estradiol was greater than that caused 

 by the estradiol alone, whereas the treat- 

 ment with 4 mg. progesterone in combina- 

 tion with 1.0 mg. estradiol resulted in an 

 inhibition of the estrogenic activity (Fig. 

 16.261. Thus progesterone may play a dual 

 role in the water metabolism of the gravid 

 female. In the presence of low titers of 

 estrogen, progesterone augments its action 

 which may be a means of insuring an ade- 

 quate fluid retention to provide for the 

 fluid requirements of the fetus. However, 

 if the titers of the estrogens and possibly of 

 other steroids affecting salt and water me- 

 tabolism became excessively high, the pro- 

 gesterone may provide a protective measure 

 by inhibiting the activity of these sub- 

 stances. This concept is in accord with re- 

 ports describing the diuretic action of pro- 

 gesterone in the iiypophysectomized rat 

 (Selye and Bassett, 1940) and the inhibi- 

 tion of the salt- and water-retaining action 

 of DOCA and cortisone by progesterone 

 (Landau, Bergenstal, Lugibihl and Kascht, 

 1955). 



G lOmg Estradiol 



X Olmg Estradiol 



A lOmg Estrodiol + 4 mg Progesterone 



A I mg Estrodiol -f 4 mg Progesterone 



TREATMENT PERIOD 



-5 5 10 15 20 25 



DAYS OF TREATMENT 



Fig. 16.26. Changes in the blood volume of 

 the ovariectomized rabbit treated with 0.1 mg. 

 and 1.0 mg. estradiol daily and with a combination 

 of the two estrogen treatments and 4 mg. proges- 

 terone. (From L. M. Horger and M. X. Zarrow, 

 Am. J. Pliysiol., 189, 407, 1957.) 



It is also of interest that no anemia was 

 observed in animals treated with various 

 combinations of estrogen and progesterone 

 (Horger and Zarrow, 1957). Progesterone 

 elicits an increase in the cell volume which 

 api^roximates that of the plasma volume. 

 Because no erythrocyte counts were made in 

 this study, it is not possible to state whether 

 this increase in the cell volume is caused 

 by a macrocytosis or an increase in the num- 

 ber of erythrocytes. Vollmer and Gordon 

 ( 1941 ) reported that progesterone caused an 

 increase in the erythrocyte count of the 

 rat but that the action was inconsistent. 

 Hence it is possible that the increase in 

 the cell volume is due to an enhancement of 

 hematopoiesis by the progesterone. This 

 possibility is not inconsistent with the 

 absence of an increase in the reticulocyte 

 count in response to these treatments since 

 a reticulocytosis usually occurs only after 

 an intense stimulation of the hematopoietic 

 tissue such as by hemorrhage. 



In view of the previous discussion, it is 

 improbable that the anemia of pregnancy 

 is due entirely to the interaction of estrogen 

 and progesterone. These hormones appear to 



