Phenobarbital‐induced phosphorylation converts nuclear receptor ROR ROR α from a repressor to an activator of the estrogen sulfotransferase gene Sult1e1 Sult1e1 in mouse livers

摘要

The estrogen sulfotransferase SULT 1E1 sulfates and inactivates estrogen, which is reactivated via desulfation by steroid sulfatase, thus regulating estrogen homeostasis. Phenobarbital ( PB ), a clinical sedative, activates Sult1e1 gene transcription in mouse livers. Here, the molecular mechanism by which the nuclear receptors CAR , which is targeted by PB , and ROR α communicate through phosphorylation to regulate Sult1e1 activation has been studied. ROR α, a basal activity repressor of the Sult1e1 promoter, becomes phosphorylated at serine 100 and converts to an activator of the Sult1e1 promoter in response to PB . CAR regulates both the ROR α phosphorylation and conversion. Our findings suggest that PB signals CAR to communicate with ROR α via serine 100 phosphorylation, converting ROR α from transcription repressor to activator of the Sult1e1 gene and inducing SULT 1E1 expression in mouse livers.