Extra-adrenal deoxycorticosterone production in hypoestrogenic pregnancies: Serum concentrations of progesterone and deoxycorticosterone in anencephalic fetuses and in women pregnant with an anencephalic fetus

In a continuing effort to define the origin of and the regulation of the production of deoxycorticosterone, we measured deoxycorticosterone and progesterone in the umbilical cord plasma of 16 anencephalic fetuses and newborn infants (21 to 45 weeks' gestation) and deoxycorticosterone, progesterone, 17β-estradiol, and estriol in the plasma of 18 women pregnant (16 to 45 week) with an anencephalic fetus. Whereas umbilical cord plasma levels of progesterone in the anencephalic fetuses were similar to those of normal abortuses and newborn infants, those of deoxycorticosterone (1.3 ± 0.21 ng/ml, mean ± SE) were significantly lower (P<0.001) than those in normal abortuses and newborn infants delivered between 31 and 42 weeks' gestation (3.94 ± 0.26 ng/ml). We found that plasma levels of deoxycorticosterone were significantly correlated (P<0.001) to those of progesterone in women pregnant with an anencephalic fetus, as well as in women pregnant with a normal fetus. Plasma levels of deoxycorticosterone (range = 0.14 to 0.92 ng/ml) in women pregnant with an anencephalic fetus were significantly lower than those in women pregnant with a normal fetus; plasma levels of progesterone were similar in both groups. The plasma levels of 17β-estradiol and of estriol were extremely low in women pregnant with an anencephalic fetus compared with those in women with a normal fetus and did not vary as a function of gestational age. In one subject who was pregnant with an anencephalic fetus, we found that estrogen treatment (100 mg of diethylstilbestrol/day) for 6 days caused a progressive increase in the serum levels of deoxycorticosterone and in the ratio of the concentration of deoxycorticosterone to that of progesterone in serum. Both the serum levels of deoxycorticosterone and the ratio of the concentration of deoxycorticosterone to that of progesterone declined after cessation of estrogen treatment. Although it could be argued that the levels of deoxycorticosterone are reduced in women pregnant with an anencephalic fetus because of decreased secretion from the hypoplastic fetal adrenal glands, we suggest that an alternative explanation is that the deficit in maternal levels of deoxycorticosterone also results from relative hypoestrogenism in such pregnancies, since we showed previously that estrogen acts to stimulate extra-adrenal steroid 21-hydroxylase activity. We suggest that among the determinants of extra-adrenal deoxycorticosterone formation in the maternal compartment are the rate of placental secretion of progesterone and the extent of estrogen-induced extra-adrenal steroid 21-hydroxylase activity.