Transcriptional Regulation of Dehydroepiandrosterone Sulfotransferase (SULT2A1) by Estrogen-Related Receptor α

The estrogen-related receptors (ERRα, -β, and -γ) are a subfamily of orphan nuclear receptors (designated NR3B1, NR3B2, and NR3B3) that are structurally and functionally related to estrogen receptors α and β. Herein we test the hypothesis that ERRα regulates transcription of the genes encoding the enzymes involved in adrenal steroid production. Real-time RT-PCR was first used to determine the levels of ERRα mRNA in various human tissues. Adult adrenal levels of ERRα transcript were similar to that seen in heart, which is known to highly express ERRα. Expression of ERRα in the adult adrenal was then confirmed using Western blotting and immunohistochemistry. To examine the effects of ERRα on steroidogenic capacity we used reporter constructs with the 5′-flanking regions of steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage (CYP11A), 3β-hydroxysteroid dehydrogenase type II (HSD3B2), 17α-hydroxylase/17,20-lyase (CYP17), and dehydroepiandrosterone sulfotransferase (SULT2A1). Cotrans...