Transcription Enhancer Factor-5 and a GATA-Like Protein Determine Placental-Specific Expression of the Type I Human 3β-Hydroxysteroid Dehydrogenase Gene, HSD3B1

The enzyme 3β-hydroxysteroid dehydrogenase/isomerase (3βHSD) is required for the biosynthesis of all active steroid hormones. It exists as multiple isoforms in humans and rodents, each a product of a distinct gene. Two isoforms, 3βHSD I and II, are expressed in a tissue-specific manner in humans. 3βHSD I is the only isoform expressed in the placenta, where it is required for the biosynthesis of progesterone and thus essential for the maintenance of pregnancy. We recently identified two transcription factors, activating protein-2γ (AP-2γ) and the homeodomain protein, distaless-3 (Dlx-3), that are expressed in both human and mouse trophoblast cells that were shown to be required for trophoblast-specific expression of the orthologous murine 3βHSD, 3βHSD VI. Although we identified specific binding sites for AP-2γ and Dlx-3 in the distal promoter of the human 3βHSD I gene, HSD3B1, it was found that these transcription factors were not involved in determining placental-specific expression of human 3βHSD I. Inst...