Intermediary metabolism of estriol in pregnancy

Estriol (E3), the most abundant estrogen in pregnancy is produced predominantly in the placenta from androgen precursors of fetal origin. The estriol so formed is secreted efficiently into the maternal circulation where it is converted to 4 conjugates--estriol-3-sulfate (E3-3S), estriol-16-glucosiduronate (E3- 16G ), estriol-3-glucosiduronate (E3- 3G ) and estriol-3-sulfate-16-glucosiduronate (E3-SG). The order of renal clearances is E3- 16G greater than E3- 3G greater than E3-3S approximately E3-SG. Unconjugated E3 and E3- 3G differ from the other forms of estriol in that their removal from the blood compartment is essentially irreversible. E3-3S, E3- 16G and E3-SG undergo interconversions during enterohepatic circulation and eventual partial conversion to E3- 3G . Following delivery of the fetus and placenta, unconjugated E3 is no longer detectable in the maternal serum within 1-2 h, whereas the concentrations of the conjugates decline more slowly, the rates being determined by the rates of renal clearance and enterohepatic interconversions. E3- 3G levels were dramatically elevated in a case of Group C polycystic kidney disease, providing evidence that this conjugate is indeed an end-product of estriol metabolism.