Study on metabolic pathway from dehydroepiandrosterone sulfate to estrogen in late pregnancy (Japanese)

Abstract

To investigate the metabolic pathway from dehydroepiandrosterone sulfate (DHAS) to estriol (E3) in late human pregnancy, DHAS (50 to 100 mg) was given intravenously or intraamniotically to 13 volunteers (from cases of normal pregnant women, pregnant women with a live anencephalic fetus, intrauterine fetal death or hydatidiform mole and a patient with cancer of the cervix). Urinary estrogens, serum unconjugated estrogens and urinary dehydroepiandrosterone (DHA) and 16α hydroxy dehydroepiandrosterone (16α OH DHA) were measured before and after injection. Brown's method (1955) was used to measure urinary tract fractions of estrogens, estrone (E1), estradiol (E2) and estriol (E3). Serum unconjugated estrogens, estrone (SE1), estradiol (SE2) and estriol (SE3) were determined by a radioimmunoassay technique. Urinary DHA and 16α OH DHA were separated by a modification of the method of Lakshmanan and Lieberman (1954) and by thin layer chromatography, and estimated by the method of Oertel and Eiknes (1959). Results obtained were as follows: In seven cases of pregnancy with a live anencephalic fetus the excretion of urinary estriol was very low and the ratio of E3/E1+E2 was much less than that in normal pregnancy. In five women with a live anencephalic fetus the effect of intravenously injected DHAS was studied. In each case there was a remarkable difference in urinary E3, E1 and E2, while no remarkable difference between the ratio of E3/E1+E2 before and after administration of DHAS was found. DHAS was given intraamniotically to two women with a live anencephalic fetus. A greater rise of the ratio of E3/E1+E2 after administration of DHAS was found, compared to the control. DHAS circulating in the maternal organism is converted to E3 largely via a phenolic pathway (DHAS-E1-E3), whereas DHAS circulating within the feto placental compartment is converted to E3 via both phenolic and neutral intermediates (DHAS-6α-OH-DHAS-E3). The ratio of urinary 16α-OH-DHA/DHA in pregnancy with a live anencephalic fetus was greater than that in non pregnant women. This suggests that 16α hydroxylase activity in pregnancy is elevated. Increases in serum unconjugated E1, E2 and E3 after intravenous administration of DHAS in three pregnant women with a live anencephalic fetus were found.