Abstract
Ever since Csapo (1) presented his progesterone block theory the plasma concentration of progesterone and estradiol has been rigorously studied by a series of investigators. Although some experimental evidence in animals supports this hypothesis, the results of studies in man do not (2, 3, 4). On the other hand it is more reasonable to think that the biological activity of the hormones will be governed by the concentrations in the tissue. Recent data from studies in man, rabbit and guinea-pig in this laboratory clearly showed that plasma concentrations of estradiol and progesterone were poorly reflected in the myometrium (see 5 for reference). Another interesting feature that was revealed by this comparative analysis was that during pregnancy the concentration of progesterone in the human myometrium was 50 to 100 times greater than that in the guinea-pig myometrium in spite of similar concentrations in the plasma in the two species (5). These observations led us to read-dress the question of the role of progesterone in the maintenance of pregnancy.
On the basis of extensive data obtained in the past few years mainly in this laboratory (see 5, 6, 7), I propose that the major function of progesterone in pregnancy is to lower estradiol concentration in the myometrium, leading to a higher progesterone/estradiol (P/E2) ratio which in turn is required for the maintenance of pregnancy. The regulation or rather the lowering of estradiol concentration in the myometrium by progesterone is probably achieved by an inhibitory action of progesterone on estrogen receptor synthesis (7, 8, 9). In the guinea-pig and also to a great extent in the rabbit, uterine estradiol during pregnancy is low due to a low estradiol concentration in the plasma (5). The need for inhibition of estradiol receptor synthesis in these species in contrast to man therefore does not arise. It may not seem surprising then that almost all of the plasma progesterone in the pregnant guinea-pig is prevented from entering the uterus by virtue of its complete binding to the progesterone-binding globulin (5). This may in fact be an added but important function of progesterone-binding globulin which to my knowledge is found specifically in the pregnant guinea-pig circulation (5).
Key Words: