The absence of expression in mouse hepatocytes indicates that Cyp1b1 impacts hepatic gene expression through extra-hepatocyte signaling processes. This signaling can proceed locally via adjacent endothelia and stellate cells or systemically through endocrine and neuronal control mechanisms. These effects may occur directly or be realized through developmental intervention. Cyp1b1-ko mice retain normal caloric intake (Figure S1A), indicating improved energy utilization. This metabolic homeostasis is also regulated via ER-α, aromatase and VMH leptin receptors [33–34, 68]. Cyp1b1 is appreciably expressed in the hypothalamus [69] and diminished metabolism of estradiol in Cyp1b1-ko mice has been shown to affect blood pressure [12].
