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

The estrogen sulfotransferase SULT1E1 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 alpha communicate through phosphorylation to regulate Sult1e1 activation has been studied. ROR alpha, 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 alpha phosphorylation and conversion. Our findings suggest that PB signals CAR to communicate with ROR alpha, via serine 100 phosphorylation, converting ROR alpha from transcription repressor to activator of the Sult1e1 gene and inducing SULT1E1 expression in mouse livers.