Equine type estrogens produced by a pregnant woman carrying a Smith-Lemli-Opitz syndrome fetus

The equine-type estriols 1,3,5(10),7-estratetraene-3,16 alpha,17 beta-triol (16 alpha-hydroxy-17 beta-dihydroequilin) and 1,3,5(10),6,8-estrapentaene- 3,16 alpha,17 beta-triol (16 alpha-hydroxy-17 beta-dihydroequilenin) consti tuted over half of the estrogens excreted by a woman carrying a Smith-Lemli -Opitz syndrome (SLOS) affected fetus. The steroids were characterized by g as chromatography-mass spectrometry (GC/MS): and mass spectra of the dehydr o estriols as trimethylsilyl ethers are illustrated. SLOS is associated wit h 7-dehydrocholesterol (7DHC), delta 7-reductase deficiency; the enzyme cat alyzing the final step in cholesterol biosynthesis. Identification of these equine estrogens show that an estrogen biosynthetic pathway parallel to no rmal is functional in the fete-placental unit and uses 7DHC as precursor, t herefore P450scc, P450c17, and 3 beta HSD and P450arom are all active on 7- dehydrometabolites. Patients with affected fetuses have low plasma estriol values (probably due to deficient production of the cholesterol precursor) and this is often a warning sign which instigates further evaluation for SL OS. The estriol deficiency is not quantitatively made up by the dehydrometa bolites, and the combined excretion was found to be about one-third of the mean of gestational age matched controls. The importance of these findings lies in the potential value of dehydroestr iol measurement for non-invasive diagnosis of SLOS at mid-gestation. Curren tly diagnosis relies on imaging, since SLOS is a malformation syndrome, and measurement of 7DHC levels in amniotic fluid and chorionic villus tissue.