Metabolism of 17α‐ethynylestradiol by intact liver parenchymal cells isolated from mouse and rat

Liver parenchymal cells isolated by perfusion from female C3H/HeN‐MTV+Nctr mice and Sprague‐Dawley rats were incubated with [6,7‐³H] 17α‐ethynylestradiol (EE₂). The incubates were individually fractionated into free steroid (organic phase), steroid conjugates (aqueous), and bound steroids (macromolecular pellet). The rat had significantly less total free radioactive steroid but significantly more total conjugated and irreversibly bound radioactivity than the mouse. However, when the metabolic conversion of EE₂ was compared in the rat and the mouse on a cellular basis (metabolic clearance per 10⁶ cells), the rat was found to be less efficient than the mouse. The two species were essentially equivalent in their covalent binding when expressed on a per 10⁶ cell basis. Purification of the free radiolabeled steroids on LH‐20 demonstrated the mouse to have the parent compound and an identifiable 2‐OH‐EE₂ fraction. The rat had EE₂ and an identifiable 2‐methoxy‐EE₂ fraction. A major metabolite fraction for both species was very nonpolar and, although not identified, was found to be ethynylated as demonstrated by silver‐sulfoethylcellulose chromatography. The conjugate fractions of the mouse were indicative of glucuronide conjugation, whereas the rat had additional conjugate fractions suggestive of sulfo‐conjugation.