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-3,16α,17β-triol (16α-hydroxy-17β-dihydroequilin) and 1,3,5(10),6,8-estrapentaene-3,16α,17β-triol (16α-hydroxy-17β-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 feto-placental unit and uses 7DHC as precursor, therefore P450scc, P450c17, and 3βHSD 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...