Estrogen Production

CONCENTRATIONS IN THE CIRCULATION

The placenta becomes the primary source of estrogens (Fig. 7) after approximately week 9 of
human pregnancy (23% of gestational length ). As a result of extensive 16-hydroxylation of c19
steroids within the fetus, large quantities of estriol are produced by the placenta during human
pregnancy. A fourth estrogen, estetrol, is also produced uniquely but in relatively low levels during
human pregnancy.
172

173

174

Plasma concentrations of estrone, estradiol, and estriol increase as human pregnancy

progresses with daily excretion rates at term approximating 2, 1, and 40 mg, respectively. , In
humans, plasma concentrations of estradiol near term range from 6 to 30 ng/mL. , In women
with threatened first-trimester abortion, abnormal estradiol concentrations are highly associated
with a subsequent pregnancy loss. Moreover, a 50% spontaneous abortion rate has been observed
among women having a mutation in the amino terminal region of the estrogen receptor involved in
transcription. In the baboon, reduction of maternal estrogen levels to less than 0.1 ng/mL by
daily administration of an inhibitor of placental estrogen synthesis resulted in a 66% incidence of
abortion during early gestation that was prevented by treatment with exogenous estradiol. Low
serum estradiol concentrations during the third trimester are also associated with poor obstetric
outcome. , Taken together, these observations suggest that estrogen plays a critically important
role in the maintenance of primate pregnancy, but others have refuted this notion because
pregnancy is maintained in most women having low estrogen levels resulting from deficiencies in
various placental enzymes. , Interestingly, in those cases, although maternal estradiol levels are
markedly reduced, concentrations approximate 0.45 ng/mL, or 10 -9 mol/L, a concentration that
approximates the dissociation constant for estradiol binding to its receptor. Differences in the
outcome of pregnancy in various women with estrogen deficiency suggest that the important
biologic effects of estradiol can be achieved with available receptor and concentrations of estrogen
sufficient to interact with it. It would appear that in both human and nonhuman primate
.pregnancy, estrogen is produced in considerable excess
172 174

175 176

177

178

179

180 181

182

183 184

185