Diminished conjugation of products of mixed-function oxidation in perfused livers from hypophysectomized rats.

Abstract

The rates of metabolism of 7-ethoxycoumarin and subsequent conjugation of 7-hydroxycoumarin were studied in perfused livers from hypophysectomized or sham-operated control rats. Rates of 7-ethoxycoumarin O-deethylation were higher both in perfused livers and microsomes from hypophysectomized compared to sham-operated controls. However, conjugation of 7-hydroxycoumarin formed from 7-ethoxycoumarin was markedly decreased by hypophysectomy. p-Nitrophenol conjugation was also impaired in perfused livers from hypophysectomized rats. During infusion of 59-65 microM of p-nitrophenol into hypophysectomized livers, rates of glucuronidation were diminished by 45% (6.83 +/- 0.49 to 3.78 +/- 0.31 mumol/g/h) and rates of sulfation were decreased by 50% (1.25 +/- 0.12 to 0.62 +/- 0.07 mumol/g/h). Phenol sulfotransferase activity was decreased 57% by hypophysectomy, which is the likely explanation for the decrease in sulfate conjugation. However, hypophysectomy did not affect glucuronyltransferase activity. Perfused livers from hypophysectomized rats released glucose, pyruvate and lactate at lower rates than livers from sham-operated rats. Furthermore, infusion of glucose into perfused livers from hypophysectomized rats, but not sham-operated controls, increased the rate of conjugation. The results demonstrate that hypophysectomy decreased rates of conjugation in perfused livers, and that the decreased glucuronidation rates are probably the result of diminished carbohydrate reserves.