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) constituted over half of the estrogens excreted by a woman carrying a Smith-Lemli-Opitz syndrome (SLOS) affected fetus. The steroids were characterized by gas chromatography-mass spectrometry (GC/MS): and mass spectra of the dehydro estriols as trimethylsilyl ethers are illustrated. SLOS is associated with 7-dehydrocholesterol (7DHC), delta 7-reductase deficiency; the enzyme catalyzing the final step in cholesterol biosynthesis. Identification of these equine estrogens show that an estrogen biosynthetic pathway parallel to normal is functional in the fete-placental unit and uses 7DHC as precursor, therefore 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 SLOS. The estriol deficiency is not quantitatively made up by the dehydrometabolites, 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 dehydroestriol measurement for non-invasive diagnosis of SLOS at mid-gestation. Currently diagnosis relies on imaging, since SLOS is a malformation syndrome, and measurement of 7DHC levels in amniotic fluid and chorionic villus tissue.