Metabolism of territrem A in liver microsomes from Wistar rats: 2. Sex differences and regulation with gonadal hormones and phenobarbital

The aim of the present study was to assess the effects of sex difference on metabolism of territrem A (TRA) by liver microsomes from 7-wk-old Wistar rats. Metabolism of TRA to 2-dihydro-4 beta -demethylterritrem A (MA(2)) through 4 beta -hydroxymethyl-4 beta -demethylterritrem A (MA(1)) and 4 beta -oxo-4 beta -demethylterritrem A (MAX) was observed in intact male rats. However, in intact female rats only MA, was formed, although the amount of MA(1) formed in females was much less than in males. Phenobarbital pretreatment enhanced this step and was not affected by gonadectomy. In the gonadectomized rats of both sexes, MA(2) was formed from TPA when the animals were further treated by testosterone and was significantly enhanced by treatment with phenobarbital. However, estradiol treatment or estradiol in combination with phenobarbital treatment did not affect MA(2) formation from TRA in gonadectomized rats.