Estrogen-triggered activation of GTP cyclohydrolase 1 gene expression: Role of estrogen receptor subtypes and interaction with cyclic AMP

Although estradiol increased GTPCH promoter activity in the presence of estrogen receptors, it attenuated the response of the promoter and endogenous gene to cyclic AMP, suggesting the crosstalk between estrogen and cyclic AMP pathways in the regulation of GTPCH gene expression. These findings reveal the significance of estrogen in modulating regulation of rate limiting enzyme in the (6R)-5,6,7,8-tetrahydrobiopterin biosynthesis, which may have implications for sex-related differences in vulnerability in related disorders.